Journal of Shanghai Jiao Tong University (Medical Science)

Adenosine monophosphate deaminase 3 regulates the bone marrow reconstitution ability of hematopoietic stem cells through the CREB/ADCY10 signaling pathway

Zhang Yue, Xia Yiqiu, He Xiaoxiao, Chen Chiqi, Zhang Yaping, Wang Yu, Zheng Junke, Xie Li, Yu Zhuo

2026, 46 (6): 693-704.
doi: 10.3969/j.issn.1674-8115.2026.06.001

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Objective ·To investigate the role of adenosine monophosphate deaminase 3 (AMPD3) in hematopoietic stem cells (HSCs) and acute myeloid leukemia (AML). Methods ·Hematopoietic system-specific Ampd3 knockout mice (Vav1-Cre;Ampd3^fl/fl) and control mice (Ampd3^fl/fl) were generated using the Cre/LoxP system. An in vivo competitive bone marrow transplantation assay was performed to examine the effects of Ampd3 on the bone marrow reconstitution and lineage differentiation capacities of HSCs. RNA sequencing (RNA-seq) was performed to compare differentially expressed genes and enriched pathways in HSCs from Vav1-Cre;Ampd3^fl/fl and Ampd3^fl/fl mice. Real-time reverse transcription quantitative PCR (RT-qPCR) was used to validate differentially expressed genes and identify potential targets. Short hairpin RNAs (shRNAs) targeting the identified geneswere constructed, and in vivo and in vitro rescue experiments were conducted to validate their functions. Western blotting, immunofluorescence staining, and dual-luciferase reporter assays were then employed to explore the upstream regulatory factors. An MLL-AF9-induced AML model was established, and serial in vivo transplantation experiments were performed to observe the impact of Ampd3 on disease progression. Results ·In the competitive bone marrow transplantation assay, Vav1-Cre;Ampd3^fl/fl mice exhibited significantly higher bone marrow reconstitution ability than the Ampd3^fl/fl mice, but no differences were observed in myeloid, T lymphocyte, or B lymphocyte lineage differentiation. RNA-seq analysis revealed significant enrichment of the cyclic adenosine monophosphate (cAMP) signaling pathway and other pathways in HSCs from Vav1-Cre;Ampd3^fl/fl mice, and among the differentially expressed genes, adenylate cyclase 10 (Adcy10) was significantly upregulated. Knockdown of Ampd3 in 32D cells significantly accelerated cell proliferation, whereas simultaneous knockdown of Adcy10 markedly slowed the proliferation. In vivo rescue experiments showed that further knockdown of Adcy10 in Ampd3-deficient hematopoietic stem and progenitor cells significantly reduced their bone marrow reconstitution capacity, suggesting that Adcy10 was a downstream target of Ampd3. Furthermore, the expression level of phosphorylated cAMP response element-binding protein (p-CREB) in HSCs from Vav1-Cre;Ampd3^fl/fl mice was significantly increased compared with that in Ampd3^fl/fl mice. Immunofluorescence staining also revealed stronger nuclear localization of p-CREB in HSCs from Vav1-Cre;Ampd3^fl/fl mice. Dual-luciferase reporter assays confirmed that CREB was able to activate the transcription of Adcy10, accompanied by increased expression of both p-CREB and total CREB. The CREB inhibitor 666-15 significantly downregulated the mRNA and protein expression levels of Adcy10. However, hematopoietic-specific knockout of Ampd3 did not affect AML progression. Conclusion ·Hematopoietic-specific deletion of Ampd3 in mice leads to elevated p-CREB expression, which activates Adcy10 transcription and thereby enhances the bone marrow reconstitution capacity of HSCs. Ampd3 does not affect AML progression, suggesting that Ampd3 is mainly involved in regulating HSC function under stress conditions.

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Research progress in the evolutionary characteristics and prevention and control of Nipah virus

Jin Dawei, Zhang Xinxin, Wan Zilin, Guo Jinzheng, Ren Lili

2026, 46 (6): 705-712.
doi: 10.3969/j.issn.1674-8115.2026.06.002

Abstract ( 28 )

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Nipah virus (NiV) is a highly lethal single-stranded negative-sense RNA virus designated by the World Health Organization (WHO) as a priority pathogen for pandemic preparedness. NiV has fruit bats as its natural reservoir and can infect humans through direct contact, consumption of contaminated food, and person-to-person transmission, causing severe diseases such as acute encephalitis and acute respiratory distress syndrome, with case fatality rates ranging from 40% to 75%. Based on whole-genome sequence homology and geographical distribution patterns, NiV has differentiated into two major genetic lineages, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B). NiV-M is primarily transmitted via intermediate hosts (pigs and horses) and outbreaks can be controlled through culling of infected intermediate hosts, whereas NiV-B can directly spill over from fruit bat reservoirs to humans, exhibits greater person-to-person transmissibility, and shows endemic transmission characteristics. Current NiV outbreak prevention and control efforts face multiple challenges, including persistent viral genome evolution, lack of lineage-discriminating capability of diagnostic assays, and the absence of licensed human vaccines. This review systematically summarizes the evolutionary characteristics of NiV, its cross-species transmission patterns, recent advances in vaccine and antiviral drug development, analyzes the impact of viral evolution on surveillance strategies, and provides recommendations for optimizing prevention and control strategies from a pandemic preparedness perspective.

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Research progress in development of SHP2 inhibitors and their application in tumor therapy

Shen Yuxiao, Li Xiaoguang, Ba Qian

2026, 46 (6): 713-720.
doi: 10.3969/j.issn.1674-8115.2026.06.003

Abstract ( 28 )

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Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2), encoded by the PTPN11 gene, is an important molecule in the non-receptor protein tyrosine phosphatase (PTP) family. It can regulate multiple core signaling pathways, including RAS/mitogen-activated protein kinase (RAS/MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1). SHP2 affects the proliferation, differentiation, survival, and apoptosis of tumor cells, and plays an important role in mediating tumor drug resistance. In the tumor microenvironment (TME), SHP2 plays a key role in the regulation of immunosuppression. It can inhibit the activation and effector functions of T cells by participating in the downstream signal transduction of immune checkpoints, while also regulating the status of immune cells such as macrophages and promoting tumor immune escape. Given the dual roles of SHP2 in driving tumor growth and mediating immunosuppression, SHP2-targeted therapy has become a promising anti-tumor strategy. SHP2 inhibitors can not only inhibit the carcinogenic signaling pathways, but also effectively relieve the inhibition of SHP2 on T cells and reprogram the immune microenvironment, thus producing synergistic anti-tumor effects. At the same time, the combined application of SHP2 inhibitors with existing therapies also shows great potential in overcoming drug resistance and improving efficacy, which is an important direction in current tumor treatment research. Based on this, this review summarizes the biological functions and related signaling networks of SHP2, as well as its mechanisms in tumorigenesis and immune escape, and analyzes the research progress of SHP2-targeted drug development and the application prospects of combination treatment strategies, in order to provide new ideas and references for tumor treatment research.

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Study on the effects of fangchinoline in regulating T lymphocyte subsets in an animal model of Sjogren's syndrome

Niu Shutong, Shi Huan, Yu Chuangqi

2026, 46 (6): 721-731.
doi: 10.3969/j.issn.1674-8115.2026.06.004

Abstract ( 22 )

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Objective ·To elucidate the therapeutic effects of fangchinoline (FAN) on Sjogren's syndrome in Nod/LtJ mice, its regulatory effects on T cell subsets, and its potential molecular targets. Methods ·The mice were divided into four groups: control group, disease group, hydroxychloroquine (HCQ)-treated group, and FAN-treated group. The HCQ-treated group received oral gavage every other day, and the FAN-treated group received intraperitoneal injections every other day, both for 4 weeks. Body weight, salivary flow rate, submandibular gland index, and splenic index were measured in the fifth week. Levels of anti-Ro/SSA, anti-La/SSB, and immunoglobulin G (IgG) antibodies in the peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Lymphocyte infiltration in the submandibular glands was assessed by hematoxylin-eosin (HE) staining. The distribution of splenic T lymphocyte subsets was analyzed by flow cytometry. Potential targets of FAN were identified by target fishing, PAGE enrichment, and mass spectrometry. Molecular docking was performed to analyze binding affinity and predict binding sites. Results ·FAN treatment significantly improved salivary flow reduction in Nod/LtJ mice (P=0.046) and markedly alleviated lymphocyte infiltration in the submandibular glands (P=0.044). The levels of anti-Ro/SSA antibodies in peripheral blood were significantly reduced (P=0.041). Flow cytometry results indicated that FAN altered the distribution of splenic T lymphocyte subsets. T helper 1 (Th1) (P=0.014), T helper 17 (Th17) (P=0.011), T follicular helper (Tfh) (P=0.002), and T helper 2 (Th2) (P=0.018) cells were decreased, and regulatory T cells (Treg) (P=0.014) were increased. Furthermore, target fishing coupled with mass spectrometry identified pyruvate kinase M2 (PKM2) as a potential target for FAN. Molecular docking simulations indicated a stable interaction between FAN and PKM2. Conclusion ·FAN exerts discernible therapeutic effects on Sjogren's syndrome symptoms in Nod/LtJ mice. These effects are associated with modulation of T lymphocyte subset distribution and may be mediated through PKM2. These findings highlight the promising therapeutic potential of FAN in managing Sjogren's syndrome.

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Structural insights into the recognition of endogenous nucleosomes by the human SUV39H1- HP1α complex

Hu Qiong, Huang Jing

2026, 46 (6): 732-739.
doi: 10.3969/j.issn.1674-8115.2026.06.005

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Objective ·To analyze the three-dimensional structure of the human histone methyltransferase SUV39H1 in complex with heterochromatin protein 1α bound to the endogenous nucleosome core particle (NCP^endo) through cryo-electron microscopy (cryo-EM). Methods ·The human SUV39H1 gene was cloned into the pMLink vector with an N-terminal 6×His-3×Flag tag, and the human HP1α gene was cloned into the pMLink vector with an N-terminal 2×HA tag. The SUV39H1-HP1α complex was co-expressed in Expi293F mammalian suspension cells through transient transfection using polyethylenimine. The expressed complex was sequentially purified by affinity chromatography with anti-DYKDDDDK resin and glycerol gradient ultracentrifugation combined with chemical cross-linking. Subsequently, cryo-EM data collection and single-particle reconstruction were performed to obtain the three-dimensional electron density map of the SUV39H1-HP1α-NCP^endo complex. AlphaFold2-predicted models were docked into the EM density using UCSF Chimera. Results ·The SUV39H1-HP1α-NCP^endo complex was successfully obtained with high purity by affinity chromatography and glycerol density gradient ultracentrifugation. Cryo-EM single-particle reconstruction yielded a preliminary density map of the SUV39H1-HP1α-NCP^endo complex at a resolution of approximately 3.6 Å (1 Å=10^-10 m). In addition to the nucleosome core particle, an extra discontinuous peripheral density was observed. Based on its size and spatial distribution, preliminary structural fitting suggested that this density may correspond to the SET domain of SUV39H1. Conclusion ·The density map of the SUV39H1-HP1α-NCP^endo complex was obtained by cryo-EM and single-particle reconstruction. Although the peripheral density is discontinuous and does not support reliable atomic modeling, its size and spatial features are consistent with the SET domain (including pre-SET, SET, and post-SET sub-modules) of SUV39H1. In addition, the chromo domain (CD) of SUV39H1 and HP1α were not been clearly resolved, suggesting that these regions may exhibit conformational dynamics within this complex.

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hsa_circ_0001900 enhances the proliferation, migration, and invasion of Wilms tumor cells while suppressing apoptosis through acceleration of G1/S cell cycle transition

Zhu Rundong, Gao Zhiqiang, Xiang Bin, Hong Peng, Hu Zaihong, Cui Kongkong, Long Teng, Zhang Zhijun, Ma Wei, Chen Pengfei, Shi Qinlin, Tian Xiaomao, Wei Guanghui

2026, 46 (6): 740-750.
doi: 10.3969/j.issn.1674-8115.2026.06.006

Abstract ( 32 )

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Objective ·To explore the function and potential mechanism of circular RNA (circRNA) hsa_circ_0001900 in Wilms tumor. Methods ·Lentivirus was used to construct cell lines with stable overexpression of hsa_circ_0001900 (WIT-49, WT-CLS1, and SK-NEP-1), and specific small interfering RNA (siRNA) was used to transiently silence this molecule. Transcriptome sequencing was performed on hsa_circ_0001900-overexpressing and control cell lines, and its potential biological functions were preliminarily explored based on enrichment analysis of differentially expressed genes. cell counting kit-8 (CCK-8) assay, wound-healing assay, Transwell assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were used to evaluate the effects of hsa_circ_0001900 on the proliferation, migration, invasion, and apoptosis of Wilms tumor cells. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were further adopted to screen Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways potentially regulated by hsa_circ_0001900. Finally, flow cytometry was used to detect cell cycle distribution and apoptosis to verify the related pathways experimentally. Results ·PCR assays confirmed that the expression of hsa_circ_0001900 was significantly upregulated in Wilms tumor cell lines (WIT-49, WT-CLS1, and SK-NEP-1) compared with normal human embryonic kidney HEK-293T cells. Cell lines with stable overexpression and transient silencing were successfully constructed using lentivirus and siRNA, respectively. Enrichment analysis of transcriptomic data showed that differentially expressed genes were mainly enriched in pathways associated with cell proliferation, cell cycle regulation, migration, and apoptosis. In vitro experiments further confirmed that overexpression of hsa_circ_0001900 promoted the proliferation, migration, and invasion of Wilms tumor cells, while silencing this molecule significantly inhibited the above malignant biological behaviors and induced cell apoptosis. Mechanistically, enrichment analysis centered on hsa_circ_0001900 revealed that GSEA and GSVA jointly enriched the cell cycle signaling pathway. Flow cytometry detection showed that stable overexpression of hsa_circ_0001900 markedly shortened the G1 phase and prolonged the S phase in WIT-49, WT-CLS1, and SK-NEP-1 cells, suggesting that this molecule may drive the malignant progression of Wilms tumor by facilitating G1/S phase transition. Conclusion ·hsa_circ_0001900 is specifically highly expressed in Wilms tumor cells. This molecule promotes the proliferation, migration, and invasion of Wilms tumor cells and inhibits cell apoptosis by accelerating the G1/S cell cycle transition.

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Thrombus enhancement on dual-phase CT angiography in the evaluation of thrombus composition and source in hyperacute ischemic stroke

Yao Tingting, Guo Yuanyuan, Xiong Yijia, Li Yuehua, Wei Xiao′er

2026, 46 (6): 751-758.
doi: 10.3969/j.issn.1674-8115.2026.06.007

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Objective ·To evaluate the enhancement of thrombi in patients with different subtypes of hyperacute ischemic stroke using pre-interventional non-contrast computed tomography (NCCT) and dual-phase computed tomography angiography (CTA). Methods ·From January 2018 to October 2020, the clinical data of patients with hyperacute ischemic stroke who presented to the Emergency Department of Neurology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively analyzed and the patients with hyperacute ischemic stroke caused by occlusion of the M1 or M2 segment of the middle cerebral artery were included. All patients were classified according to the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification criteria for acute ischemic stroke. The clinical and imaging data of these patients obtained at admission and during subsequent follow-up were analyzed, with particular emphasis on the initial NCCT and CTA images (n=113). Additionally, histological examinations of the retrieved thrombi were performed following mechanical thrombectomy (n=53). Differences in CT values were calculated between NCCT and conventional arterial-phase CTA (Δ₁), as well as between NCCT and late arterial-phase CTA (Δ₂). Percentages of each component on hematoxylin-eosin-stained sections were measured by ImageJ. The differences in thrombus composition among the groups and the correlation between CT value changes and thrombus composition were analyzed. Results ·The Δ₁ value in the large-artery atherosclerosis (LAA) group was lower than that in the cardioembolic group (P=0.001). No significant difference was found in the Δ₁value between the cardioembolic group and the cryptogenic group (P=0.840). The Δ₂ value in the LAA group was higher than that in the cryptogenic group (P=0.035). No significant difference was found in the Δ₂value between the cardioembolic group and the cryptogenic group (P=0.691). The Δ₂ value was significantly higher than the Δ₁ value in the LAA group (P<0.001). No significant differences were found between Δ₁and Δ₂ values in the cardioembolic group or the cryptogenic group (both P>0.05). The percentage of red blood cells in the thrombi from patients with LAA stroke was significantly higher than that in the cardioembolic group and the cryptogenic group (both P<0.05). The Δ₁ value was negatively correlated with the percentage of red blood cells (r=-0.511, P<0.001) and positively with the percentage of fibrin/platelet aggregates (r=0.502, P<0.001). Conclusion ·Thrombus enhancement on admission NCCT and dual-phase CTA can help identify the origin of thrombi in patients with hyperacute ischemic stroke. In the patients with LAA stroke, thrombi show enhancement in the conventional arterial phase with more prominent enhancement in the late arterial phase. In the patients with cardioembolic or cryptogenic stroke, thrombi also manifest enhancement in the conventional arterial phase, while the enhancement degree in the late arterial phase shows no difference from that in the conventional arterial phase.

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Clinical benefits of icodextrin-based peritoneal dialysis solution and its impact on cardiovascular risk in patients undergoing peritoneal dialysis

Feng Linhong, Wu Di, Zhu Yingchun, Xu Jiarui, Zhang Chong, Wang Yakun

2026, 46 (6): 759-769.
doi: 10.3969/j.issn.1674-8115.2026.06.008

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Objective ·To evaluate the clinical benefits of icodextrin-based peritoneal dialysis solution (ICO) in patients undergoing peritoneal dialysis (PD), and analyze its impact on the incidence of major adverse cardiovascular events (MACE). Methods ·This multicenter, prospective, and randomized controlled trial enrolled 120 patients undergoing PD from three clinical centers between January 2023 and January 2024. The participants were randomly assigned in a 1:2 ratio to the ICO group (n=40) or the control group (n=80). Patients in the ICO group received 1.5% or 2.5% glucose-based PD solution during the day and a nightly 8‒12 h dwell of 7.5% ICO. Patients in the control group received 1.5% or 2.5% glucose-based PD solution during the day and a once-daily 8‒12 h dwell of 2.5% glucose-based PD solution. The intervention period was 12 months. Demographic data of the patients were collected, as well as laboratory parameters, overhydration (OH) values, peritoneal equilibration test results, and echocardiographic parameters before and after the intervention. The incidences of MACE, hospitalization, and death were recorded in both groups. Kaplan-Meier survival curves were used to compare the differences in MACE incidence, hospitalization rate, all-cause mortality, and cardiovascular mortality between the two groups. Multivariable Cox regression analysis was performed to identify factors associated with MACE in patients undergoing PD. Results ·After 12 months of intervention, the ICO group showed significantly lower levels of fasting blood glucose, glycated hemoglobin, body mass index, OH values, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) compared with the control group (all P<0.05). The ICO group also had significantly higher 24-h ultrafiltration volume, residual renal Kt/V (r-Kt/V), and total Kt/V (t-Kt/V) than the control group (all P<0.05). Echocardiographic data revealed that the ICO group had significantly lower left ventricular end-diastolic diameter (LVEDd) and left ventricular mass index (LVMI) (both P<0.05), and significantly higher left ventricular ejection fraction (LVEF) (P<0.05) compared with the control group. Kaplan-Meier survival analysis showed that the ICO group had significantly lower cardiovascular mortality (Log-rank P=0.048) and MACE incidence (Log-rank P=0.043) than the control group. No significant differences were observed in all-cause mortality or hospitalization rate between the two groups. Multivariable Cox regression analysis identified pre-existing cardiovascular disease (HR=1.57, 95%CI 1.07‒2.33, P=0.035), high peritoneal transport status (HR=1.65, 95%CI 1.08‒2.89, P=0.045), and elevated NT-proBNP levels (HR=1.38, 95%CI 1.13‒2.89, P=0.013) as independent risk factors for MACE in patients undergoing PD, while the use of ICO (HR=0.35, 95%CI 0.17‒0.89, P=0.012) was identified as a protective factor. Conclusion ·ICO improves glucose metabolism, alleviates volume overload, enhances dialysis adequacy, and reduces the incidence of MACE and cardiovascular mortality in patients undergoing PD.

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Effects of maxillary sinus pneumatization on bone thickness of infrazygomatic crest for miniscrew implant placement

Zhang Shuting, Yang Xin

2026, 46 (6): 770-777.
doi: 10.3969/j.issn.1674-8115.2026.06.009

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Objective ·To investigate the effect of the degree of maxillary sinus pneumatization (MSP) on total bone thickness (BT) and cortical bone thickness (CBT) along the insertion path of miniscrew implants (MIs) placed in the infrazygomatic crest (IZC) region. Methods ·Young adult orthodontic patients aged 18‒34 years were included. Cone-beam computed tomography (CBCT) data collected at the initial visit were analyzed. Based on the distance from the apex of the mesiobuccal root of the maxillary first molar to the sinus floor (sinus floor-apex distance, SFA), the samples were divided into three groups: high sinus floor group (HS group, SFA≥3 mm), middle sinus floor group (MS group, 0 mm ≤ SFA < 3 mm), and low sinus floor group (LS group, SFA<0 mm). MIs were placed at angles of 50° or 60° relative to the palatal plane at the apex levels of the mesiobuccal root of the maxillary first molar (U6M), the distobuccal root of the maxillary first molar (U6D), and the mesiobuccal root of the maxillary second molar (U7M), as well as 2 mm cranial to these apex levels. BT and CBT along the insertion path were measured and compared. Results ·A total of 87 patients were included: HS group (n=33) with an SFA of (4.88±1.32) mm, MS group (n=27) with an SFA of (1.57±0.76) mm, and LS group (n=27) with an SFA of (-1.82±0.96) mm. At the U6M and U6D insertion sites, BT and CBT in all groups decreased as the degree of MSP increased. At U7M, no statistically significant differences in BT and CBT were found between the HS and MS groups, but both were greater than those in the LS group (all P<0.05). No statistically significant differences in BT were observed between the MS and LS groups at different sagittal sites. In the HS group, BT gradually decreased in the distal direction. All groups showed a trend toward thinner BT in the more cranial direction. In the HS group, at the apex level, a 50° insertion angle resulted in greater BT than a 60° insertion angle; at 2 mm cranial to the apex, no significant difference in BT was found between the 50° and 60° insertion angles. In the MS group, at both the apex level and 2 mm cranial to the apex, a 60° insertion angle provided greater BT than a 50° insertion angle. In the LS group, at 2 mm cranial to the apex, a 60° insertion angle provided greater BT than a 50° insertion angle; however, regardless of whether a 50° or 60° insertion angle was used, sufficient BT could not be obtained in the LS group. Conclusion ·BT and CBT decreased significantly with increasing MSP in the IZC region. For HS patients, MI placement in the IZC region is generally safe. For MS patients, MI placement at the apex level is relatively safe. For LS patients, MI placement in the IZC region is not recommended.

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Mendelian randomization study on the causal relationship between dietary factors and insomnia symptoms

Cui Guoyu, Wang Qiuyun, Tan Haozhou, Yang Qianzi, Luo Yan

2026, 46 (6): 778-785.
doi: 10.3969/j.issn.1674-8115.2026.06.010

Abstract ( 22 )

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Objective ·To investigate the causal relationships between multiple dietary factors and insomnia symptoms by using a two-sample Mendelian randomization (MR) approach. Methods ·Single nucleotide polymorphisms (SNPs) associated with various dietary factors and insomnia symptoms were extracted from publicly available Genome-Wide Association Studies (GWAS) databases and used as instrumental variables. The inverse variance weighted (IVW) method was applied as the primary analysis, complemented by the weighted median, MR-Egger regression, weighted mode, and simple mode methods. Heterogeneity was assessed by using Cochran's Q test, while horizontal pleiotropy was evaluated by using the MR-Egger intercept test. Leave-one-out analyses were conducted to examine the influence of individual SNPs on the overall results. Results ·Six dietary factors were identified as having potential causal associations with insomnia symptoms. Alcohol intake (OR=1.07, 95%CI 1.01‒1.12, P=0.018) and poultry intake (OR=1.12, 95%CI 1.00‒1.24, P=0.041) were positively associated with insomnia symptoms.. In contrast, oily fish (OR=0.91, 95%CI 0.84‒1.00, P=0.047), cereals (OR=0.92, 95%CI 0.87‒0.99, P=0.017), fresh fruit (OR=0.84, 95%CI 0.72‒0.98, P=0.022), and dried fruit (OR=0.77, 95%CI 0.69‒0.85, P=5.256×10^-7) intake were negatively associated with insomnia symptoms. After Bonferroni correction, the causal relationship between dried fruit intake and insomnia symptoms remained statistically significant. Conclusion ·The findings support potential causal associations between different dietary factors and insomnia symptoms, providing genetic evidence for further investigation into the role of dietary factors in sleep health and potential intervention strategies.

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RCAS-TVA-mediated genetic targeting of oligodendrocyte lineage cells in vivo

Zhang Xiaoyue, Shen Xi, Li Nannan, Hong Xiaoqi, Tong Xiaoping

2026, 46 (6): 786-794.
doi: 10.3969/j.issn.1674-8115.2026.06.011

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Objective ·To develop an in vivo genetic manipulation strategy based on the replication-competent avian sarcoma/leukosis virus (RCAS)‒tumor virus receptor A (TVA) gene delivery system to specifically target oligodendrocyte lineage cells (OLCs), enabling efficient labeling and targeted modulation of these cells. Methods ·Using RCAS-EGFP (enhanced green fluorescent protein) as the backbone vector, shRNA sequences targeting G protein-coupled receptor 17 (GPR17) or a non-targeting Scramble control sequence were inserted. Following viral packaging, viral titers were determined using the fluorescent focus units (FFU). In Olig2-TVA-IRES-Cre transgenic mice, which allow specific RCAS infection of OLCs, stereotactic injections of either the RCAS-shRNA(Scramble)-EGFP (control group) or the RCAS-shRNA(GPR17)-EGFP (knockdown group) were performed into the hippocampus (HPC) or the arcuate nucleus (ARC), respectively. Immunofluorescence staining was conducted for the oligodendrocyte lineage transcription factor 2 (Olig2), the neuronal marker neuronal nuclei (NeuN), and the astrocytic marker glial fibrillary acidic protein (GFAP) to validate viral transduction specificity. To validate knockdown efficiency of the virus, immunofluorescence staining for the target protein GPR17 was performed in both the control group and the knockdown group. The expression levels of GPR17 protein in the ARC were measured by Western blotting before and after knockdown. To evaluate the impact of GPR17 knockdown on cellular differentiation, immunofluorescence staining for the oligodendrocyte precursor cell marker platelet-derived growth factor receptor α (PDGFRα) and the mature oligodendrocyte marker CC1 was performed in both groups. Results ·The packaged viral titer was 5×10⁷ PFU/mL. Immunofluorescence analysis revealed high specificity of infection, with 77.99% and 75.02% of GFP-positive cells co-localizing with Olig2 in the HPC and ARC, respectively. Additionally, co-localization of GFP with NeuN or GFAP was scarcely detected. The knockdown efficiency was confirmed by a significant reduction in GPR17-positive cells among GFP-positive populations. In the HPC, the percentage of GPR17⁺/GFP⁺cells decreased from 71.85% in the control group to 34.34% in the knockdown group (P<0.001), indicating a marked reduction in GPR17 expression. In the ARC, the proportions of GPR17⁺/GFP⁺ double-positive cells were 78.12% in the control group and 31.72% in the knockdown group. Western blotting results showed that the expression level of GPR17 protein in the ARC was significantly reduced following viral knockdown. In the HPC, CC1⁺ mature oligodendrocytes exhibited an increasing trend after GPR17 knockdown, though the difference was not statistically significant. However, PDGFRα⁺ oligodendrocyte precursor cells decreased significantly (P<0.001). In the ARC, knockdown of GPR17 significantly increased CC1⁺ mature oligodendrocytes and reduced PDGFRα⁺ oligodendrocyte precursor cells (both P<0.001). Conclusion ·The RCAS‒TVA gene delivery system enables efficient in vivo labeling and targeted knockdown of genes in oligodendrocyte lineage cells.

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Research progress in sleep manifestations related to major depressive disorder and its potential mechanisms

Zhu Mo, Chen Jun

2026, 46 (6): 795-800.
doi: 10.3969/j.issn.1674-8115.2026.06.012

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Major depressive disorder (MDD) is a common psychiatric disorder. It features high prevalence and high disability rates globally, imposing a heavy disease burden on society and families. Sleep problems are highly prevalent among patients with MDD, which are not only one of the core symptoms of MDD, but are also closely related to its onset, persistence, and recurrence, severely impairing patients' social functioning and quality of life. This article systematically reviews the common sleep problems in patients with MDD and the associated neurobiological mechanisms, and summarizes current clinical intervention strategies and their underlying mechanisms, aiming to provide scientific theoretical support for the clinical intervention of MDD and its comorbid sleep problems.

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Review of mechanism of interleukin regulatory network in inflammatory bowel disease

Li Mengru, Wang Haiqiang

2026, 46 (6): 801-809.
doi: 10.3969/j.issn.1674-8115.2026.06.013

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Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a heterogeneous group of disorders characterized by chronic and recurrent gastrointestinal inflammation. The pathophysiological mechanisms of IBD are complex, involving numerous factors, including genetics, environmental exposure, dysbiosis of the gut microbiota, and abnormal immune responses, with the disruption of immune homeostasis being a central pathological component. Studies have shown that abnormal regulation of cytokine networks plays a key role in the onset and progression of IBD. Among these, interleukins (ILs), as a class of important signaling molecules, have attracted widespread attention in the pathogenesis and clinical treatment of IBD, and targeted therapies against ILs have demonstrated significant efficacy. This article systematically elucidates the association between ILs and IBD, provides an in-depth analysis of the mechanisms by which ILs function in the pathogenesis of IBD, and discusses the imbalance between pro-inflammatory ILs (such as IL-6, IL-17, and IL-23) and the anti-inflammatory IL-10, as well as the regulation of their corresponding signaling pathways. It also summarizes IL-targeted therapeutic strategies, including the clinical validation of biologics and novel therapies, with the aim of providing new tactics for the clinical management of IBD.

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Research progress in role of corneal nerve density-sensation-reflex axis imbalance in neurotrophic keratitis

Xie Xinyi, Liu Hanxuan, Ni Ke, Li Jin, Huang Xiaolin

2026, 46 (6): 810-814.
doi: 10.3969/j.issn.1674-8115.2026.06.014

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The corneal nerve density-sensation-reflex axis plays an important role in maintaining the physiological homeostasis of the ocular surface. An in-depth understanding of the function of this axis is essential for the prevention and treatment of neurotrophic keratitis and the protection of visual function. Neurotrophic keratitis is one of the typical pathological models of axis imbalance. It is caused by trigeminal nerve injury, which leads to a reduction in corneal nerve density and corneal innervation, resulting in decreased corneal sensation and impairment of the protective blink reflex. This article reviews the anatomical and physiological basis of this axis and summarizes the quantitative evidence and molecular mechanisms underlying the effects of reduced nerve density on axis function. In addition, the assessment methods of axis function are discussed, including the quantification of corneal nerve parameters by in vivo confocal microscopy, the evaluation of corneal sensation using the Cochet-Bonnet esthesiometer, and the assessment of blink function by the corneal reflex test. In terms of therapeutic strategies, this article summarizes interventions targeting axis function, including epithelial trophic support and sensory restoration as well as corneal reinnervation. Furthermore, potential novel therapeutic approaches and therapeutic targets for the restoration of axis function are discussed.

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Research progress in role of T helper 17 cells and interleukin-17 in occurrence and development of osteoarthritis under regulation of gut microbiota

Gong Jian, Han Jiyu, Wan Daqian

2026, 46 (6): 815-823.
doi: 10.3969/j.issn.1674-8115.2026.06.015

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Osteoarthritis (OA) is a leading cause of disability worldwide, and the understanding of its pathogenesis is undergoing a paradigm shift from a simple "wear-and-tear" disease to a metabolic and low-grade inflammatory disorder. The gut microbiota, as a crucial regulator of host T helper 17 (Th17) cells, exhibits complex bidirectional modulatory characteristics. On one hand, microbial metabolites (such as short-chain fatty acids, tryptophan metabolites, and secondary bile acids) help maintain the balance between Th17 cells and regulatory T (Treg) cells, thereby exerting anti-inflammatory and protective effects. These effects are mediated through epigenetic modifications, such as inhibition of histone deacetylase (HDAC), and activation of specific receptors including G-protein-coupled receptor 43 (GPR43), aryl hydrocarbon receptor (AHR), and G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5). On the other hand, structural components of the microbiota (such as lipopolysaccharides and bacterial extracellular vesicles) activate pro-inflammatory pathways via pattern recognition receptors, thereby promoting Th17 cell differentiation. Further studies have shown that gut-derived Th17 cells and their effector cytokine cytokine interleukin-17 (IL-17) serve as a pivotal link connecting gut dysbiosis and joint pathology. After migrating to the joints, Th17 cells and IL-17 act as inflammatory "amplifiers". They not only induce synovial fibroblast activation and inflammatory cascades, but also directly drive cartilage matrix degradation, senescence, and ferroptosis, while promoting abnormal subchondral bone remodelling, ultimately leading to comprehensive destruction of the joint structure. This review aims to summarize the role of the "gut microbiota-Th17/IL-17 immune" axis in the pathogenesis and progression of OA, as well as the related molecular mechanisms. Elucidating the underlying molecular mechanisms of this axis holds promise for providing novel strategies for OA treatment targeting the gut microbiota.

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A case of atypical hemolytic-uremic syndrome induced by severe acute respiratory syndrome coronavirus 2

Deng Jiayi, Wang Guangpu, Bai Shoujun, Li Ji

2026, 46 (6): 824-828.
doi: 10.3969/j.issn.1674-8115.2026.06.016

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Atypical hemolytic-uremic syndrome (aHUS) is a rare and life-threatening thrombotic microangiopathy (TMA) characterized by uncontrolled activation of the complement system's alternative pathway. In recent years, accumulating clinical evidence and case reports have established severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as a significant trigger for aHUS. This report describes a male patient with a prior history of hemolytic anemia associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency. He was admitted because of chest tightness and chest pain for two days. During hospitalization, he progressively developed typical features of aHUS, including microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Concurrently, nucleic acid testing for SARS-CoV-2 yielded positive results. Based on the patient's medical history, clinical presentation, laboratory findings, and the exclusion of other causes of TMA, a diagnosis of SARS-CoV-2-induced aHUS was established. Following admission, the patient received a multimodal therapeutic regimen consisting of glucocorticoids, plasma exchange (PE), and eculizumab. With timely and standardized intervention, his condition was effectively controlled and remained stable. This case may provide a reference for the clinical diagnosis and management of SARS-CoV-2-associated aHUS, particularly in patients with a history of hemolytic disorders.

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