Major depressive disorder (MDD) is a common mental disorder, whose pathogenesis has not been fully elucidated. Recent studies have shown that gut microbiota can regulate the permeability of blood-brain barrier (BBB) through microbiota-gut-brain axis, thereby affecting the function of brain regions related to emotion and participating in MDD development. This article reviews the recent advance in gut microbiota in the pathogenesis and treatment of MDD, with the aim of providing a reference for clinical treatment of MDD.

Major depressive disorder (MDD) is a common mental disorder, whose pathogenesis has not been fully elucidated. Recent studies have shown that gut microbiota can regulate the permeability of blood-brain barrier (BBB) through microbiota-gut-brain axis, thereby affecting the function of brain regions related to emotion and participating in MDD development. This article reviews the recent advance in gut microbiota in the pathogenesis and treatment of MDD, with the aim of providing a reference for clinical treatment of MDD.

Objective:To investigate the feasibility of in vitro prime editor (PE) and adenine base editor (ABE) for correction the pathogenic variant of the human deafness gene SLC26A4 c.1229C>T. Methods:From March 2023 to April 2024, prime editing guide RNA (pegRNA) expression vectors as well as single guide RNA (sgRNA) were designed and constructed for the SLC26A4 c.1229C>T variant, and the feasibility of correction was performed in the HEK293T mutation model, the correction efficiency was analyzed by deep sequencing. Results:A mutant cell model of SLC26A4 c.1229C>T was successfully established. Correction was achieved in the SLC26A4 c.1229C>T mutant cell model using PE and ABE8e. Deep sequencing analysis revealed the correction efficiencies of (31.89±0.77)% and (41.07±2.28)%, respectively. Conclusion:In this study, a new base correction strategy based on the human deafness gene SLC26A4 is proposed, which provides a viable reference for gene therapy of deafness caused by SLC26A4 gene mutation.

Objective:To describe the clinical manifestations, genetic mutation site, diagnosis, and treatment of a patient with multisystem proteinopathy type 1 (MSP1) caused by valosin-containing protein ( VCP) gene mutation, and to improve clinicians′ understanding of this disease. Methods:A retrospective analysis was performed on clinical and genetic data from a confirmed VCP gene missense mutation-associated MSP1 case diagnosed at the Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Southeast University in January 2024. A 12-month follow-up and systematic literature review were performed for comprehensive analysis. Results:The 53-year-old male patient presented with progressive limb weakness over 7 months. Neurological examination demonstrated tongue fasciculations, asymmetric proximal muscle weakness in all four limbs, left patellar hyperreflexia, positive right Chaddock sign, and bilateral Hoffmann signs. Electrophysiological studies demonstrated extensive neurogenic damage. Lower-limb muscle magnetic resonance imaging (MRI) showed selective fatty infiltration in specific muscle groups. Biceps brachii biopsy pathology revealed rimmed vacuoles and grouped atrophy of typeⅡfibers. Immunofluorescence confirmed aberrant aggregation of VCP within atrophic myofibers, showing co-localization with p62 and transactive response DNA binding protein 43 (TDP-43). Whole-genome sequencing identified a heterozygous c.463C>T (p.Arg155Cys) missense mutation in exon 5 of the VCP gene, classified as a likely pathogenic mutation according to the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The patient was diagnosed with MSP1 with amyotrophic lateral sclerosis and inclusion body myopathy as the main clinical manifestation based on clinical manifestations, electrophysiology, imaging, histopathology, and genetic findings. After 12 months of riluzole therapy, disease progression remained relatively slow. Literature review identified 67 relevant articles, revealing 87 VCP mutation genotypes and 19 clinical phenotypes. Conclusions:MSP1 is a genetically and phenotypically heterogeneous spectrum of multisystem degenerative disorders. This case represents the first reported VCP-related MSP1 in China, characterized by amyotrophic lateral sclerosis combined with inclusion body myopathy. Riluzole treatment demonstrates slowed disease progression over 1 year.

Objective:To summarize the clinical and genetic characteristics of 23 children with pathogenic ACAN gene variants, enhance the understanding of this disorder, and explore possible regulatory mechanisms. Methods:A retrospective case series summary.The clinical characteristics and genetic analysis results of 23 children with ACAN gene variants treated in the Department of Endocrinology, Genetics and Metabolism, Children′s Hospital of Soochow University from January 2016 and September 2024 were analyzed retrospectively.Transcriptome sequencing was performed on peripheral blood samples from 3 of affected children and 3 age-matched healthy children as controls.Differentially expressed genes (DEGs) in the peripheral blood transcriptome profiles were identified.Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to explore the potential signaling pathways involved. Results:Among the 23 cases, there were 13 males and 10 females, aged from 2 years and 8 months to 12 years old, with 11 cases presenting advanced bone age.Thirteen cases were treated with growth hormone (GH), including 6 cases who received concomitant gonadotropin-releasing hormone analogue therapy.The treatment duration ranged from 3 to 70 months, resulting in varying degrees of height improvement in all treated patients.Transcriptomic analysis identified 811 DEGs, with 516 up-regulated and 295 down-regulated.GO and KEGG enrichment analyses revealed that the heterozygous ACAN variants were significantly associated with FcγR-mediated phagocytosis, nuclear factor-κB signaling pathway, the intestinal immune network for IgA production, rheumatoid arthritis, and systemic lupus erythematosus signaling pathways. Conclusions:The predominant clinical manifestations of patients with ACAN gene variants are short stature and advanced bone age.Although GH provocation tests may indicate normal GH levels, GH therapy can be effective in improving height.Immune-related factors may play a role in the pathogenesis of this disorder.

Peritoneal metastasis is a common form of distant metastasis in patients with colorectal cancer, and it is typically associated with a poor prognosis. The development of peritoneal metastasis involves complex molecular mechanisms and multifactorial regulation of the tumor microenvironment. Due to the presence of the blood-peritoneal barrier, only a small amount of systemic medication reaches the peritoneal cavity, resulting in limited efficacy against peritoneal metastasis. Intraperitoneal administration shows significant therapeutic advantages as it can directly target the tumor microenvironment, maintain high local drug concentrations, and reduce systemic toxicity. Intraperitoneal chemotherapy, especially hyperthermic intraperitoneal chemotherapy, has become a cornerstone therapeutic strategy in the clinical treatment of peritoneal metastasis. When selecting chemotherapy drugs and drug combinations, pharmacokinetic properties, efficacy, and safety must be comprehensively considered to optimize the treatment outcomes. In addition, the unique microenvironment of the peritoneal cavity provides new treatment approaches for biological treatment strategies, including antitoxins, vaccines, immune checkpoint inhibitors, etc. Techniques such as pressurized intraperitoneal aerosol chemotherapy and novel drug delivery systems demonstrate potential for enhanced efficacy, offering promising alternatives to improve patient outcomes. This article will review peritoneal barrier characteristics, intraperitoneal drug transport, intraperitoneal chemotherapy, and intraperitoneal biological therapies, thereby establishing a theoretical framework for precision therapy in colorectal cancer peritoneal metastasis.

Objective To investigate the effects of dienogest on pain relief and inflammation in endometriosis(EMs),as well as its impact on the brain-derived neurotrophic factor(BDNF)/tropo-myosin receptor kinase B(TrkB)and nuclear factor kappa-B(NF-κB)/NOD-like receptor protein 3(NLRP3)inflammatory pathways.Methods An allograft method was used to establish an EMs rat model.The rats were randomly divided into sham-operated group(n=16),model group(n=16),low-dose dienogest group(n=16),medium-dose dienogest group(n=16)and high-dose dienogest group(n=16).After 7 days of treatment,the implantation volume and writhing response frequency were recorded.Enzyme-linked immunosorbent assay(ELISA),reverse transcription-polymerase chain reaction and Western blotting were employed to measure the expression levels of vascular endothelial growth factor(VEGF),inducible nitric oxide synthase(iNOS),interleukin(IL)-6,IL-1β and tumor necrosis factor(TNF)-α in the EMs rat models.Serum levels of BDNF,TrkB,NF-κB and NLRP3 were detected.Results Compared with model group,dinorgestrel significantly reduced ectopic endo-metrial volume and torsion response of EMs(P＜0.05).Compared with model group,dinorgestrel significantly decreased the expression of VEGF,iNOS,IL6,IL-1 β and TNF-α in EMs model(P＜0.05).In addition,compared with model group,dienogest significantly decreased the expressions of BDNF,TrkB,NF-κB and NLRP3 in ectopic endometrium(P＜0.05).Conclusion Dinorgestrel can relieve EMS-related dysmenorrhea and inflammation,and its mechanism of action may be partly mediated by BDNF/TrkB pathway and NF-κB/NLRP3 pathway.

ObjectiveTo obtain the epidemiological characteristics of re-positive cases infected with SARS-CoV-2 in Pudong New Area from March to July 2022, including clinical manifestations, duration of a negative nucleic acid conversion after tested for re-positive, and length of time from the discharge of the initial infection to the most recent re-positivity, so as to provide a scientific basis for the prevention and control of COVID-19. MethodsA questionnaire survey was conducted among the re-positive cases infected with SARS-CoV-2 after discharged from hospital/quarantine facility in Pudong New Area, and descriptive epidemiological methods were used for characteristics analysis. ResultsA total of 2 422 re-positive cases met the inclusive and exclusive criteria, with males accounting for 61.02%. The age distribution mainly fell between 18 and <60 years old, accounting for 62.39%. Clinical manifestations were predominantly asymptomatic (72.15%), followed by cough (12.03%) and sore throat (6.58%). Among the stratified randomized sample of 416 individuals, there were statistically significant differences in symptoms (χ²=262.667, P<0.001), clinical typing (χ²=12.996, P=0.001), and duration of a negative nucleic acid conversion (χ²=142.578, P<0.001) between the initial positive and re-positive instances. Besides, statistically significant differences in symptoms (χ²=13.696, P=0.016) and self-perception of the severity of re-infection (χ²=7.923, P=0.048) between the initial and re-positive cases were observed by different genders. ConclusionAmong re-positive cases, males experienced milder symptoms compared to females, and the self-perception of symptoms during re-positivity is milder than that in the initial positive infection. The length of time for negative nucleic acid conversion during the initial positive period is shorter than that during the re-positive period.

By reconstructing the integrated Chinese and western medicine diagnostic and treatment system， the "Two Reconstructions" theoretical framework establishes a standardized pathway of "classification-staging-syndrome differentiation"， which improves the accuracy of disease identification and strengthens the capacity for full-course intervention； in addition， by reconstructing the modern materia medica system， it innovatively integrates the traditional properties and efficacy of Chinese herbal medicinals with modern pharmacological mechanisms， forming a "state-target co-regulation" precise medication model， and builds a dose-effect theoretical system for prescriptions and medicinals， thereby enhancing both the targeting accuracy and dosage precision of therapeutic interventions. The "Two Reconstructions" theorecitcal framework is a key strategy for enhancing clinical efficacy. It can precisely identify "states" and "targets" for directed intervention， shift the focus of prevention and treatment earlier to enable full-cycle management， establish standardized paradigms for reproducible and evaluable efficacy， and expand the scope of clinical practice to address conditions without typical syndromes and critical illnesses. As a systematic pathway for innovation in TCM， this theoretical framework provides valuable insights and references for promoting the high-quality development of integrative Chinese and western medicine.

Objective:To compare the differences in clinical characteristics among the patients at clinical high risk for bipolar disorder(CHR-BD),the patients with bipolar disorder(BD),and the healthy controls(HC)at low risk,and to provide the basis for the diognasis and treatment of CHR-BD.Methods:For the first time,the BD risk criteria and prospective structured assessment tools were jointly used in outpatients aged 16-30 years,and 43 CHR-BD patients were included to ensure the accuracy of the assessment.Meanwhile,33 BD patients and 32 HC subjects were also enrolled.The clinical symptoms,neurocognitive function,and global functional levels of the subjects in the three groups were evaluated using observer-rated and self-rated tools.The CHR-BD and BD groups were combined,and Logistic regression analysis was used to identify the independent influencing factors related to diagnostic status;Pearson or Spearman correlation analysis was used to analyze the correlations between the global functional levels and the symptoms or neurocognitive characteristics of the patients in CHR-BD and BD groups.Results:There were statistically significant differences in the scores of symptom and global functional level scales among HC,CHR-BD,and BD groups(P<0.05).Compared with HC group,the scores of mood symptoms(anxiety,depression,and mania/hypomania),psychotic symptoms,total affective temperament questionnaire scores,and some dimensions(cyclothymic,depressive,irritable,and anxious temperaments)in CHR-BD and BD groups were significantly increased(P<0.001),while the global functional levels were significantly decreased(P<0.001).Compared with BD group,the lowest global functional level score in the past year in CHR-BD group was significantly increased(P=0.022),while the current global functional level score was significantly decreased(P=0.005).No significant differences were observed in neurocognitive function scores among the three groups(P>0.05).The lowest global functional level score in the past year was an independent influencing factor for BD diagnosis[odds ratio(OR)=0.952,95%confidence interval(CI):0.917-0.988,P=0.010].In both CHR-BD and BD patients,the current global functional levels were negatively correlated with depressive(r=-0.417,P=0.005;r=-0.617,P<0.001)and anxiety symptoms(r=-0.360,P=0.018;r=-0.506,P=0.003).In BD patients,the current global functional level was negatively correlated with lifetime manic/hypomanic symptoms(r=-0.360,P=0.039),psychotic symptoms(r=-0.502,P=0.003),and affective temperament scores(r=-0.479,P=0.005),while the lowest global functional level in the past year was negatively correlated with lifetime manic/hypomanic symptoms(r=-0.391,P=0.024).Conclusion:CHR-BD patients share similar mood symptom characteristics with BD patients,and their global functional levels are negatively correlated with depressive and anxiety symptoms.BD patients exhibit worse lowest global functional levels in the past year,and their global functional levels are negatively correlated with manic/hypomanic symptoms.