Objective : To investigate the effect of chromosome instability(CIN) associated gene polypeptide N-acetylgalactosaminyltransferase 7(GALNT7) on proliferation and apoptosis of HCT116 colon cancer cells. Methods : The HCT116 cell line withGALNT7knockdown was constructed by lentiviral infection. The correlation betweenGALNT7and CIN was verified by chromosome spread assay. The effect ofGALNT7on cell proliferation was detected by live cell counting, and the effect ofGALNT7on cell cycle distribution was detected by flow cytometry and Western blot. Caspase-3 activity and Western blot assays were used to detect the effect ofGALNT7on apoptosis. Results : HCT116 cells showed a slower proliferation rate upon knocking down ofGALNT7, and exhibited a more scattered karyotype distribution and a phenotype of increased degree of CIN. Inhibition ofGALNT7in HCT116 cells resulted in cell cycle arrest, upregulation of P21 and downregulation of CDK6 protein levels, as well as increased levels of Caspase-3 activity, cleaved PARP1 and PUMA protein expression, and decreased levels of BCL-2 protein expression. Conclusion TheGALNT7gene may promote proliferation and inhibit apoptosis of HCT116 colon cancer cells through the suppression of CIN generation.

ObjectiveTo study the effect of Zuoguiwan on the development of skin barrier in the neonatal rat model of congenital kidney deficiency and unveil the underlying mechanism. MethodsSixty rats were paired in a female-to-male ratio of 2∶1， and the pregnant rats were assigned into control， congenital kidney deficiency， and low- and high-dose （2 and 8 g·kg^-1， respectively） Zuoguiwan groups. The pregnant rats in other groups except the control group were exposed to chronic unpredictable mild stress for the modeling of congenital kidney deficiency. The rats in the control group and congenital kidney deficiency group were administrated with normal saline by gavage， and those in Zuoguiwan groups with Zuoguiwan suspension by gavage from day 1 of pregnancy. The serum level of interleukin-6 （IL-6） in the neonatal rats on the day of birth was determined by enzyme-linked immunosorbent assay. The full-thickness skin of neonatal rats on the day of birth was removed from the same position on the back and stained with hematoxylin-eosin for observation of histopathological changes， measurement of skin thickness， and counting of hair follicles. Terminal deoxynucleotidyl transferase-mediated nick end labeling was used to detect the apoptosis of skin tissue cells. The expression of interleukin-6 receptor （IL-6R） and interleukin-17A （IL-17A） in the skin tissue was assessed by immunohistochemistry and Western blot， and the expression of occludin， connexin 43 （Cx43）， and zonula occludens-1 （ZO-1） in the skin tissue was assessed by immunofluorescence and Western blot. ResultsCompared with those in the control group， the neonatal rats in the congenital kidney deficiency group showed a rise in the serum IL-6 level （P<0.01）， decreases in stratum corneum thickness， skin thickness， and number of hair follicles （P<0.01）， increases in the expression of IL-6R and IL-17A in the skin tissue （P<0.01） and the number of apoptotic cells （P<0.01）， and decreases in the expression of occludin， Cx43， ZO-1 （P<0.05）. Compared with the congenital kidney deficiency group， the low- and high-dose Zuoguiwan groups showed declines in serum IL-6 level （P<0.05）. The low-dose group showed increased number of hair follicles （P<0.05）， and the high-dose group presented thickened stratum corneum （P<0.01）， increased number of hair follicles （P<0.01）， and down-regulated expression of IL-6R and IL-17A in the skin tissue （P<0.05， P<0.01）. Both Zuoguiwan groups showcased decreased number of apoptotic cells （P<0.05， P<0.01）， and the high-dose group showed up-regulated expression of occludin， Cx43， and ZO-1 in the skin tissue （P<0.05， P<0.01）. ConclusionZuoguiwan can reduce the levels of IL-6 in the serum and IL-6R and IL-17A in the skin tissue and improve the expression of intercellular junction proteins， thereby ameliorating the abnormal development of the skin barrier in the neonatal rat model of congenital kidney deficiency.

ObjectiveTo study the effect of Zuoguiwan on the development of skin barrier in the neonatal rat model of congenital kidney deficiency and unveil the underlying mechanism. MethodsSixty rats were paired in a female-to-male ratio of 2∶1， and the pregnant rats were assigned into control， congenital kidney deficiency， and low- and high-dose （2 and 8 g·kg^-1， respectively） Zuoguiwan groups. The pregnant rats in other groups except the control group were exposed to chronic unpredictable mild stress for the modeling of congenital kidney deficiency. The rats in the control group and congenital kidney deficiency group were administrated with normal saline by gavage， and those in Zuoguiwan groups with Zuoguiwan suspension by gavage from day 1 of pregnancy. The serum level of interleukin-6 （IL-6） in the neonatal rats on the day of birth was determined by enzyme-linked immunosorbent assay. The full-thickness skin of neonatal rats on the day of birth was removed from the same position on the back and stained with hematoxylin-eosin for observation of histopathological changes， measurement of skin thickness， and counting of hair follicles. Terminal deoxynucleotidyl transferase-mediated nick end labeling was used to detect the apoptosis of skin tissue cells. The expression of interleukin-6 receptor （IL-6R） and interleukin-17A （IL-17A） in the skin tissue was assessed by immunohistochemistry and Western blot， and the expression of occludin， connexin 43 （Cx43）， and zonula occludens-1 （ZO-1） in the skin tissue was assessed by immunofluorescence and Western blot. ResultsCompared with those in the control group， the neonatal rats in the congenital kidney deficiency group showed a rise in the serum IL-6 level （P<0.01）， decreases in stratum corneum thickness， skin thickness， and number of hair follicles （P<0.01）， increases in the expression of IL-6R and IL-17A in the skin tissue （P<0.01） and the number of apoptotic cells （P<0.01）， and decreases in the expression of occludin， Cx43， ZO-1 （P<0.05）. Compared with the congenital kidney deficiency group， the low- and high-dose Zuoguiwan groups showed declines in serum IL-6 level （P<0.05）. The low-dose group showed increased number of hair follicles （P<0.05）， and the high-dose group presented thickened stratum corneum （P<0.01）， increased number of hair follicles （P<0.01）， and down-regulated expression of IL-6R and IL-17A in the skin tissue （P<0.05， P<0.01）. Both Zuoguiwan groups showcased decreased number of apoptotic cells （P<0.05， P<0.01）， and the high-dose group showed up-regulated expression of occludin， Cx43， and ZO-1 in the skin tissue （P<0.05， P<0.01）. ConclusionZuoguiwan can reduce the levels of IL-6 in the serum and IL-6R and IL-17A in the skin tissue and improve the expression of intercellular junction proteins， thereby ameliorating the abnormal development of the skin barrier in the neonatal rat model of congenital kidney deficiency.

BackgroundCurrently， the problem of depressed mood in college students is becoming more prominent. The experience of childhood maltreatment is a significant contributor to depression among college students. Although the association between the two has been confirmed， the specific psychosocial mechanisms underlying how childhood maltreatment affects college students' mental health remain insufficiently evidenced. ObjectiveTo explore the mediating role of emotion regulation difficulties in the relationship between childhood maltreatment and depression among college students， and to investigate the moderated effects of psychological resilience and family socioeconomic status， aiming to provide references for improving depressive symptoms in college students. MethodsOn 14 March 2024， a cluster sampling method was employed to recruit 751 college students from a university in Heilongjiang Province. Participants were assessed with Childhood Trauma Questionnaire （CTQ）， Difficulties in Emotion Regulation Scale （DERS）， Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， 10-item Connor-Davidson Resilience Scale （CD-RISC-10） and Family Socioeconomic Status Questionnaire. Pearson correlation analysis was adopted to examine the correlation between the scores of scales. Model 4 and model 7 in Process 4.2 were used to test the mediating effects of emotional regulation difficulties and the moderated effects of psychological resilience and family socioeconomic status. Results① A total of 712 （94.81%） valid questionnaires were collected. ② College students' CTQ score was positively correlated with DERS score and PHQ-9 score （r=0.296， 0.507， P<0.01）， and negatively correlated with CD-RISC-10 score and Family Socioeconomic Status Questionnaire score （r=-0.148， -0.229， P<0.01）. ③ The indirect effect value of difficulties in emotion regulation on the relationship between childhood maltreatment and depression was 0.091 （95% CI： 0.018~0.046）， accounting for 17.95% of the total effect. ④ The first half of the mediation model "childhood maltreatment → difficulties in emotion regulation → depression" （childhood maltreatment → difficulties in emotion regulation） was moderated by psychological resilience （β=-0.030， t=-6.147， 95% CI： -0.040~-0.020） and family socioeconomic status （β=-0.051， t=-3.929， 95% CI： -0.077~-0.026）. ConclusionChildhood maltreatment exerts both a direct effect on college students' depression and an indirect effect through emotion regulation difficulties. The childhood maltreatment → emotion regulation difficulties pathway in this mediation model is moderated by psychological resilience and family socioeconomic status. ［Funded by Qiqihar Medical University Graduate Student Innovation Fund Project （number， QYYCX2023-48）； Special Research Fund Project for Young Doctors of Qiqihar Academy of Medical Sciences （number， QMSI2021B-08）］

ObjectiveTo understand the seropositivity of neutralizing antibodies (NAb) and low-level NAb against SARS-CoV-2 infection in the community residents, and to explore the impact of COVID-19 vaccination and SARS-CoV-2 infection on the levels of NAb in human serum. MethodsOn the ground of surveillance cohort for acute infectious diseases in community populations in Shanghai, a proportional stratified sampling method was used to enroll the subjects at a 20% proportion for each age group (0‒14, 15‒24, 25‒59, and ≥60 years old). Blood samples collection and serum SARS-CoV-2 NAb concentration testing were conducted from March to April 2023. Low-level NAb were defined as below the 25^th percentile of NAb. ResultsA total of 2 230 participants were included, the positive rate of NAb was 97.58%, and the proportion of low-level NAb was 25.02% (558/2 230). Multivariate logistic regression analysis indicated that age, infection history and vaccination status were correlated with low-level NAb (all P<0.05). Individuals aged 60 years and above had the highest risk of low-level NAb. There was a statistically significant interaction between booster vaccination and one single infection (aOR=0.38, 95%CI: 0.19‒0.77). Compared to individuals without vaccination, among individuals infected with SARS-CoV-2 once, both primary immunization (aOR=0.23, 95%CI: 0.16‒0.35) and booster immunization (aOR=0.12, 95%CI: 0.08‒0.17) significantly reduced the risk of low-level NAb; among individuals without infections, only booster immunization (aOR=0.28, 95%CI: 0.14‒0.52) showed a negative correlation with the risk of low-level NAb. ConclusionsThe population aged 60 and above had the highest risk of low-level NAb. Regardless of infection history, a booster immunization could reduce the risk of low-level NAb. It is recommended that eligible individuals , especially the elderly, should get vaccinated in a timely manner to exert the protective role of NAb.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Objective To investigate the role of pulmonary neuroendocrine cells(PNEC)and γ-aminobutyric acid(GABA)in patients with pulmonary neuroendocrine tumors(PNET).Methods The pathological specimens of 29 cases of PNET treated in the eighth Medical Center of Chinese PLA General Hospital from October 2018 to January 2022 were collected.The morphological characteristics were observed by HE staining,and the expression levels of synaptophysin(Syn),chromogranin A(CgA),CD56,Ki-67,CD86 and CD163 were observed by immunohistochemical staining.Calcitonin gene-related peptide(CGRP)and glutamic acid decarboxylase(GAD)65/67 in different types of PNETs were detected by double antibody immunofluorescence co-staining,and the correlation between GAD65/67 positive PNEC and macrophage polarization was analyzed.Results The results of HE staining showed that all four types of PNET tissues had neuroendocrine(NE)characteristics:rosette structure and organ nesting or palisade pattern,but they were different,and the proportion of mitotic cells from low to high was typical carcinoid(TC),atypical carcinoid(AC),large cell neuroendocrine carcinoma(LCNEC)and small cell lung cancer(SCLC).The results of immunohistochemical staining showed that the positive expression rate of Syn and CgA and the positive degree of Syn,CgA and CD56 in carcinoid(TC and AC)were significantly higher than those in LCNEC and SCLC(P＜0.05).The Ki-67 indices of the four types of PNET are:TC＜5%,AC 5%-20%,LCNEC and SCLC＞75%respectively.The number of PNEC in carcinoid was significantly higher than that in LCNEC,SCLC and paratumoral tissues(P＜0.05),but there was no significant difference in the number of PNEC between LCNEC and SCLC and para-tumor tissues(P＞0.05).The results of immunofluorescence staining showed that the number of GAD65/67 positive cells co-expressing GAD65/67 in 95%PNEC was significantly higher than that in LCNEC,SCLC and para-tumor tissues(P＜0.05),but there was no significant difference between LCNEC and SCLC GAD65/67 positive cells and para-tumor tissues(P＞0.05).The results of immunohistochemical staining also showed that the number of CD86 positive M1 macrophages was significantly higher than that of CD163 positive M2 macrophages in para-tumor tissues(P＜0.05),while M2 macrophages were significantly more than M1 macrophages in AC,LCNEC and SCLC(P＜0.01).Correlation analysis showed that the number of GAD65/67 positive PNEC cells in PNET was negatively correlated with the number of CD163 positive M2 macrophages in tumor stroma(r=-0.6336,P=0.0174).Conclusions PNEC is the main source of GABA in lung tissue and plays an immunomodulatory role in the lung,which may be involved in the progression of PNET.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

Sepsis is a condition characterized by organ dysfunction resulting from the systemic inflammatory response triggered by an infection. Excessive inflammation and immunosuppression are intertwined, and severe cases may even develop into multiple organ failure. Studies have shown that indoleamine 2,3-dioxygenase 1-mediated tryptophan metabolism is involved in the occurrence and development of sepsis, and elevated plasma kynurenine levels and Kyn/Trp ratios are early indicators of sepsis development. In this paper, we provide a comprehensive summary of the role of IDO1 in the acute inflammatory phase of sepsis, late immunosuppression, and organ damage. This includes its regulation of inflammatory state, immune cell function, blood pressure, and other aspects. Additionally, we analyze preclinical studies on targeted IDO1 drugs. An in-depth understanding and study of IDO may help to understand the pathogenesis and clinical significance of sepsis and multiple organ damage from a new perspective and provide new research ideas for exploring its prevention and treatment methods.