Gastrointestinal dysfunction in prognosis of liver cirrhotic patients with sepsis / 中国感染控制杂志

Objective To assess the value of acute gastrointestinal injury(AGI)and intestinal fatty acid-binding protein(I-FABP)in the prognosis of liver cirrhotic patients with sepsis.Methods Clinical data of 84 liver cirrhosis patients with sepsis who were admitted to the intensive care unit(ICU)of a hospital from September 2020 to March 2023 were analyzed retrospectively,and 41 patients with decompensated liver cirrhosis during the same period were selected as the control group.Serum I-FABP level in patients was determined with enzyme-linked immunosorbent assay(ELISA).Scores of the model of end-stage liver disease(MELD)and sequential organ failure assessment(SOFA)were calculated.AGI was evaluated based on medical records.30-day and 90-day survival was observed.Correlation among variables was analyzed by Spearman correlation.Risk factors for death in patients with liver cir-rhosis and sepsis was determined by multivariate Cox regression analysis.The optimal cut-off value was determined by receiver operating characteristic(ROC)curve,and the diagnostic efficacy was compared through the area under the ROC curve(AUC).Results Both AGI grading and I-FABP level in liver cirrhosis patients with sepsis were higher than those in the control group(both P＜0.05).I-FABP level was correlated with procalcitonin(PCT),MELD,and SOFA scores in patients with liver cirrhosis and sepsis(all P＜0.05).AGI grading was positively cor-related with SOFA score(P=0.038).The 30-day and 90-day mortality of patients in the liver cirrhosis with sepsis group were 25.0％(n=21)and 35.7％(n=30),respectively.Multivariate Cox regression analysis showed that baseline I-FABP and SOFA scores were independently correlated with 30-day and 90-day survival,and the I-FABP quartile showed good prognostic differentiation efficacy.ROC curve showed that I-FABP could significantly improve the predictive effect of SOFA score on the prognosis of patients.Conclusion AGI grading and I-FABP level in liver cirrhosis patients with sepsis are elevated significantly.Serum I-FABP is associated with the prognosis of patient and can improve the predictive efficacy of SOFA score for survival.

Prediction of prognosis and identification of potential therapeutic agents for liver cancer patients based on acetyl-coa carboxylase 1-associated dendritic cell / 中国现代医生

@#Objective To investigate the expression,prognostic value of acetyl-coa carboxylase 1(ACACA)gene in liver cancer,its correlation with immune cells,and to construct a prognostic model.Methods Integrating genotype-tissue expression(GTEx)and the cancer genome atlas(TCGA)data to analyze ACACA expression in cancers and adjacent tissues,and perform prognosis analysis.Examine the correlation between ACACA and immune cells.Use GSE156625 cell RNA seq(scRNA-seq)data to study ACACA expression in dendritic cells(DCs).Construct an hepatocellular carcinoma(HCC)prognosis model based on apolipoprotein c-Ⅰ(APOC1)and apolipoprotein c-Ⅲ(APOC3),using Kaplan-Meier survival curves and time-dependent receiver operator characteristic(ROC)curves to evaluate prognostic capability,and analyze the effect of traditional Chinese medicine components on APOC1 and APOC3 through molecular docking.Results ACACA shows significant differential expression in various cancers and is associated with the prognosis of liver cancer.High expression of ACACA reduces the content of dendritic cells.APOC1 and APOC3,the major DCs marker genes,were positively correlated with ACACA expression.Using Kaplan-Meier curves,we predicted the 1-year,3-year,and 5-year overall survival(OS)probabilities for HCC patients in the TCGA cohort,and confirmed the reliability through calibration curve analysis.Salvianolic acid B,Asiaticoside,and Neohesperidin may have potential effects on APOC1 and APOC3.Conclusion ACACA is closely related to HCC prognosis,and the prognostic model based on APOC1 and APOC3 can serve as a predictive indicator.Some traditional Chinese medicine components may hold therapeutic potential for HCC treatment.

Shakuyakukanzoto Relieves Ulcerative Colitis in Mice by Regulating The Expression of NDUFS1 and Inhibiting The Polarization of Macrophages to M1 / 生物化学与生物物理进展

ObjectiveThis study aims to explore and elucidate the possible mechanism of action of Shakuyakukanzoto (SKT) in improving ulcerative colitis (UC) in mice through regulating energy metabolism and polarization of macrophages. MethodsThe mouse UC model was constructed by administering 3% dextran sulfate sodium salt (DSS), and the mice were treated with SKT intragastrically. In addition, single-cell sequencing and enrichment of metabolic pathways against two datasets, GSE21157 and GSE210415, were conducted first. Second, the extraction and metabolomics of peritoneal macrophages from UC mice were verified. Then, the pathway of differentially abundant metabolite enrichment and the correlation of UC risk were analyzed depending on univariate Mendelian randomization of two samples weighted by standard inverse variance. Finally, the results were verified by qRT-PCR, Western blot, and flow cytometry. ResultsAccording to the HE staining results, SKT can significantly alleviate colon damage caused by DSS. Macrophages, NK cells, T cells, and more than 10 different types of cells, based on single-cell sequencing analysis, are detected in the intestinal wall. In the disease group, we can conclude that the activity of 49 macrophage metabolic pathways, mainly involved in energy metabolism, is significantly upregulated through a comparison of the two datasets. In energy metabolomics, 10 and 18 types of metabolites accompanied by significantly upregulated and downregulated differential expression were identified in the treatment group and the model group, as well as the model group and the blank group, respectively. Meanwhile, these differentially expressed metabolites present an obvious correlation with glycolysis and oxidative phosphorylation. Moreover, it can be inferred that glycolysis and the oxidative phosphorylation-related gene NDUFS1 (OR: 0.56, 95% CI: 0.48-0.98, P=0.000 068) are associated with a reduced risk of UC based on the univariate Mendelian randomization of two samples weighted based on standard inverse variance. By analyzing the difference in transcription levels between the two datasets, the transcription level of NDUFS1 in UC was decreased compared with that in the normal group. The results of qRT-PCR, Western blot, and flow cytometry indicate that SKT can promote the expression of the oxidative phosphorylation protein NDUFS1 in macrophages and inhibit the M1-type polarization of macrophages. Furthermore, knockdown/overexpression of NDUFS1 can affect the effect of SKT on M1-type polarization of macrophages. ConclusionBased on the results of this study, SKT inhibits macrophage polarization toward the M1 phenotype by regulating the level of the oxidatively phosphorylated protein NDUFS1 in macrophages; hence, UC is also relieved in mice. These conclusions not only reveal the therapeutic mechanism of SKT for UC but also provide a new theoretical basis for clinical application.

High water intake induces primary cilium elongation in renal tubular cells

The primary cilium protrudes from the cell surface and functions as a mechanosensor. Recently, we found that water intake restriction shortens the primary cilia of renal tubular cells, and a blockage of the shortening disturbs the ability of the kidneys to concentrate urine. Here, we investigate whether high water intake (HWI) alters primary cilia length, and if so, what is its underlying mechanism and its role on kidney urine production. Methods: Experimental mice were given free access to normal water (normal water intake) or 3% sucrose-containing water for HWI for 2 days. Some mice were administered with U0126 (10 mg/kg body weight), an inhibitor of MEK kinase, from 2 days before HWI, daily. The primary cilium length and urine amount and osmolality were investigated. Results: HWI-induced diluted urine production and primary cilium elongation in renal tubular cells. HWI increased the expression of α-tubulin acetyltransferase 1 (αTAT1), leading to the acetylation of α-tubulins, a core protein of the primary cilia. HWI also increased phosphorylated ERK1/2 (p-ERK1/2) and exocyst complex component 5 (Exoc5) expression in the kidneys. U0126 blocked HWI-induced increases in αTAT1, p-ERK1/2, and Exoc5 expression. U0126 inhibited HWI-induced α-tubulin acetylation, primary cilium elongation, urine amount increase, and urine osmolality decrease. Conclusion: These results show that increased water intake elongates the primary cilia via ERK1/2 activation and that ERK inhibition prevents primary cilium elongation and diluted urine production. These data suggest that the elongation of primary cilium length is associated with the production of diluted urine.

Effects of Zishui Qinggan Decoction on the hippocampal protein expressions of ERK,GSK3β,CREB and BDNF in a mouse model of depression induced by chronic restraint stress / 中成药

AIM To explore the effects of Zishui Qinggan Decoction on the mouse model of depression induced by chronic restraint stress(CRS)via ERK/GSK3β/CREB/BDNF signaling pathway.METHODS Except for those of the blank group,the mice of other groups were induced into depression models by CRS,and divided into the model group,the fluoxetine hydrochloride group(10 mg/kg)and the low,medium and high dose Zishui Qinggan Decoction groups(8.835,17.670 and 35.340 g/kg)for the corresponding drug intervention and simultanous CRS treatment.The mice had their sugar water preference experiment and behavior experiment on the 7th and 14th day after administration;the observation of the hippocampal morphological changes by HE staining,the detection of the superoxide dismutase(SOD)activity and malondialdehyde(MDA)level in serum by kits,the detection of levels of serum 5-hydroxytryptamine(5-HT),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)by ELISA,the detection of the hippocampal mRNA expressions of BDNF,TNF-α and IL-1β by RT-qPCR method,and the detection of the hippocampal protein expressions of ERK1/2,p-ERK1/2,GSK3β,p-GSK3β,CREB and BDNF by Western blot method 14 days after administration.RESULTS Compared with the model group,after 14 days of administration,both fluoxetine hydrochloride group and medium-dose Zishui Qinggan Decoction group displayed increased preference rate of sugar water(P<0.01),shortened immobility time of tail suspension and forced swimming(P<0.01),improved hippocampal damage of nerve cells,decreased levels of serum MDA,TNF-α and IL-1β(P<0.05,P<0.01),increased SOD activity and 5-HT level(P<0.05,P<0.01),decreased hippocampal mRNA expressions of TNF-α and IL-1β(P<0.01),and decreased expressions of BDNF mRNA and p-ERK1/2,p-GSK3β,CREB and BDNF proteins(P<0.05,P<0.01).CONCLUSION Zishui Qinggan Decoction can improve the depression-like behaviors in mice exposed to CRS,and its mechanism may be related to the regulation of hippocampal ERK/GSK3β/CREB/BDNF signaling pathway.

Nationwide survey of internal medicine hospitalists in Korea: motivation and sustainability of a hospitalist career

Background/Aims@#Although a management fee for hospitalist service was established in Korea, the number of hospitalists required for the system to run remains outmatched. @*Methods@#In January 2020 and February 2022, before and after the establishment of the hospitalist fee system respectively, cross-sectional online surveys were conducted among internal medicine board-certified hospitalists. @*Results@#There were 59 and 64 respondents in the 2020 and 2022 surveys, respectively. The percentage of respondents who cited financial benefits as a motive for becoming a hospitalist was higher in the 2022 survey than in the 2020 survey (34.4% vs. 10.2%; p = 0.001). The annual salary of respondents was also higher in the 2022 survey than in the 2020 survey (mean, 182.9 vs. 163.0 million in South Korean Won; p = 0.006). A total of 81.3% of the respondents were willing to continue a hospitalist career in the 2022 survey. In multivariate regression analysis, the possibility of being appointed as a professor was found to be an independent predictive factor of continuing a hospitalist career (odds ratio, 4.00; 95% confidence interval, 1.09–14.75; p = 0.037). @*Conclusions@#Since the establishment of the hospitalist fee system, monetary compensation has improved for hospitalists. The possibility of being appointed as a professor could predict long-term work as hospitalists.

Mechanism of total flavonoids of Rhododendra simsii in alleviating ischemic brain injury / 中国中药杂志

This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 μg·mL~(-1)) group, and TFR(30 μg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.

Distribution of memory B cell subsets in peripheral blood of children with frequently relapsing nephrotic syndrome / 中国当代儿科杂志

OBJECTIVES@#To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease.@*METHODS@#A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed.@*RESULTS@#Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD+ memory B cells, and IgE+ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM+IgD+ memory B cells, IgM+ memory B cells, IgE+ memory B cells, IgD+ memory B cells, and IgG+ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE+ memory B cells (P<0.05).@*CONCLUSIONS@#Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE+ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.

Genotyping Characteristics of Human Fecal Escherichia coli and Their Association with Multidrug Resistance in Miyun District, Beijing / 生物医学与环境科学（英文）

OBJECTIVE@#To explore the genotyping characteristics of human fecal Escherichia coli( E. coli) and the relationships between antibiotic resistance genes (ARGs) and multidrug resistance (MDR) of E. coli in Miyun District, Beijing, an area with high incidence of infectious diarrheal cases but no related data.@*METHODS@#Over a period of 3 years, 94 E. coli strains were isolated from fecal samples collected from Miyun District Hospital, a surveillance hospital of the National Pathogen Identification Network. The antibiotic susceptibility of the isolates was determined by the broth microdilution method. ARGs, multilocus sequence typing (MLST), and polymorphism trees were analyzed using whole-genome sequencing data (WGS).@*RESULTS@#This study revealed that 68.09% of the isolates had MDR, prevalent and distributed in different clades, with a relatively high rate and low pathogenicity. There was no difference in MDR between the diarrheal (49/70) and healthy groups (15/24).@*CONCLUSION@#We developed a random forest (RF) prediction model of TEM.1 + baeR + mphA + mphB + QnrS1 + AAC.3-IId to identify MDR status, highlighting its potential for early resistance identification. The causes of MDR are likely mobile units transmitting the ARGs. In the future, we will continue to strengthen the monitoring of ARGs and MDR, and increase the number of strains to further verify the accuracy of the MDR markers.

Diminazene aceturate exacerbates renal fibrosis after unilateral ureteral obstruction in female mice

Diminazene aceturate (DIZE), an angiotensin-converting enzyme 2 (ACE2) activator, exerts anti-inflammatory and antifibrotic effects in a variety of human chronic diseases. However, the role of DIZE in kidney fibrosis and the underlying mechanism remain unclear. Therefore, we investigated the effects of DIZE on the progression of renal fibrosis after unilateral ureteral obstruction (UUO), a well-established model of chronic kidney disease. Methods: C57BL/6 female or male mice were subjected to right UUO. Mice received 15 mg/kg DIZE or vehicle (saline) daily. On the 7th day after UUO, kidneys were collected for analysis of renal fibrosis (α-smooth muscle actin, phosphorylated SMAD3, transforming growth factor (TGF)-β, Masson’s trichrome, and Sirius red staining), inflammation (macrophage infiltration, proinflammatory cytokines/ chemokines), apoptosisecrotic cell death (TUNEL and periodic acid-Schiff staining), and ACE2 activity and messenger RNA (mRNA) expression. Results: Treatment with DIZE exacerbated renal fibrosis by upregulating the profibrotic TGF-β/SMAD3 pathway, proinflammatory cytokine/chemokines (interleukin [IL]-1β, monocyte chemoattractant protein-1, IL-6, and macrophage inflammatory protein-2) levels, M2 macrophage accumulation (CD206, IL-4, IL-10, and CX3CL1), and apoptoticecrotic cell death in the obstructed kidneys of female mice but not male mice. However, DIZE treatment had no effect on ACE2 activity or mRNA expression. Conclusion: DIZE exacerbates UUO-induced renal fibrosis by aggravating tubular damage, apoptosis, and inflammation through independent of angiotensin (1–7), angiotensin II levels, and ACE2 expression/activity, rather than protecting against renal fibrosis after UUO. DIZE also has powerful effects on recruiting macrophages, including the M2-polarized subtype, in female UUO mice.

Shortening of primary cilia length is associated with urine concentration in the kidneys

The primary cilium, a microtubule-based cellular organelle present in certain kidney cells, functions as a mechano-sensor to monitor fluid flow in addition to various other biological functions. In kidneys, the primary cilia protrude into the tubular lumen and are directly exposed to pro-urine flow and components. However, their effects on urine concentration remain to be defined. Here, we investigated the association between primary cilia and urine concentration. Methods: Mice either had free access to water (normal water intake, NWI) or were not allowed access to water (water deprivation, WD). Some mice received tubastatin, an inhibitor of histone deacetylase 6 (HDAC6), which regulates the acetylation of α-tubulin, a core protein of microtubules. Results: WD decreased urine output and increased urine osmolality, concomitant with apical plasma membrane localization of aquaporin 2 (AQP2) in the kidney. After WD, compared with after NWI, the lengths of primary cilia in renal tubular epithelial cells were shortened and HDAC6 activity increased. WD induced deacetylation of α-tubulin without altering α-tubulin levels in the kidney. Tubastatin prevented the shortening of cilia through increasing HDAC6 activity and consequently increasing acetylated α-tubulin expression. Furthermore, tubastatin prevented the WD-induced reduction of urine output, urine osmolality increase, and apical plasma membrane localization of AQP2. Conclusions: WD shortens primary cilia length through HDAC6 activation and α-tubulin deacetylation, while HDAC6 inhibition blocks the WD-induced changes in cilia length and urine output. This suggests that cilia length alterations are involved, at least in part, in the regulation of body water balance and urine concentration.

The flavonoid fisetin ameliorates renal fibrosis by inhibiting SMAD3 phosphorylation, oxidative damage, and inflammation in ureteral obstructed kidney in mice

Renal fibrosis is characterized by the accumulation of extracellular matrix and inflammatory cells and kidney dysfunction, which is a major pathway in the progression of chronic kidney disease (CKD). Accumulating evidence indicates that oxidative stress plays a critical role in the initiation and progression of CKD via proinflammatory and profibrotic signaling pathways. Fisetin (3,3′,4′,7-tetrahydroxyflavone) has biological activities including antioxidant, anti-inflammatory, and anti-aging effects. Therefore, we evaluated the antifibrotic effects of fisetin on unilateral ureteral obstruction (UUO)-induced kidneys. Methods: C57BL/6 female mice were subjected to right UUO and intraperitoneally injected every other day with fisetin (25 mg/kg/ day) or vehicle from 1 hour before surgery to 7 days after surgery. Kidney samples were analyzed for renal fibrosis (α-smooth muscle actin [α-SMA] expression, collagen deposition, and transforming growth factor [TGF] β1/SMAD3 signaling pathway), oxidative damage (4-HNE and 8-OHdG expression), inflammation (proinflammatory cytokine/chemokine, macrophage, and neutrophil infiltration), and apoptosis (TUNEL staining). Cultured human proximal tubule cells were treated with fisetin before TGF-β to confirm the TGF-β downstream pathway (SMAD2/3 phosphorylation). Results: We found that fisetin treatment protected against renal fibrosis by inhibiting the phosphorylation of SMAD3, oxidative damage, inflammation, apoptotic cell death, and accumulation of profibrotic M2 macrophages in the obstructed kidneys. In cultured human proximal tubular cells, fisetin treatment inhibited TGF-β1–induced phosphorylation of SMAD3 and SMAD2. Conclusion: Fisetin alleviates kidney fibrosis to protect against UUO-induced renal fibrosis, and could be a novel therapeutic drug for obstructive nephropathy.

Discussion on the surgical technique of laparoscopic anatomical hepatic segmentectomy for hepatocellular carcinoma / 中华肝胆外科杂志

With the continuous development of laparoscopic hepatectomy for the treatment of hepatocellular carcinoma in recent years, laparoscopic anatomical hepatic segmentectomy has become increasingly improved, including anatomical segmentectomy, subsegmentectomy and combined segmentectomy. The above surgical procedures involve a variety of technical means, requiring the surgeon to be familiar with intrahepatic anatomy and possess extensive experience in ultrasound technology and laparoscopic surgery. This article discussed the key techniques of laparoscopic anatomical hepatic segmentectomy for hepatocellular carcinoma based on our clinical practice.

Hepatic pedicle-first approach for laparoscopic anatomical hepatectomy for the central segments: 19 cases report / 中华肝胆外科杂志

Objective:To assess the safety and feasibility of hepatic pedicle-first approach laparoscopic anatomical hepatectomy for central segments.Methods:The clinical data of 19 patients with hepatocellular carcinoma who underwent hepatic pedicle-first approach laparoscopic anatomical hepatectomy for the central segments in the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital from September 2020 to January 2023 were retrospectively analyzed. In this procedure, hepatic pedicles of the central segments were divided first to delineate the ischemic demarcation and guide the liver parenchymal transection. The methods of operation, operation time, intraoperative blood loss, postoperative complications and hospital-stay were analyzed.Results:Hepatic pedicle-first approach laparoscopic anatomical hepatectomy for the central segments was successfully performed in all patients, including 5 cases of segment Ⅳ, 2 cases of segment Ⅳ+ Ⅷ, 3 cases of segment Ⅳ+ ventral segment Ⅷ, 3 cases of segment Ⅳa+ Ⅴ+ Ⅷ and 6 cases of segment Ⅴ+ Ⅷ. The mean operation time, intraoperative blood loss and postoperative hospital stay was (253.1±86.1) min, [ M( Q1, Q3)] 100.0(100.0, 250.0) ml, and (5.1±1.2) d respectively. There was no intraoperative blood transfusion and postoperative complications. Conclusion:Hepatic pedicle-first approach can help delineate the segemental demarcation in laparoscopic anatomical hepatectomy for the central segments, which is technically feasible and worth more practice.

Molecular epidemiological characteristics of human rhinovirus in adults with upper respiratory tract infection in Nanjing / 中华微生物学和免疫学杂志

Objective:To analyze the clinical and epidemiological features of human rhinovirus (HRV) infection in adult patients with upper respiratory tract infection (URTI) in Nanjing.Methods:Epidemiological data of adult patients with URTI in Nanjing from October 2021 to September 2022 were collected. Clinical specimens were collected and subjected to quantitative reverse transcription polymerase chain reaction (qRT-PCR) for the detection of 14 common respiratory viruses. The VP4/VP2 genes in HRV-positive samples were amplified and sequenced. Then a phylogenetic tree was constructed.Results:A total of 399 pharyngeal swabs were collected from patients with URTI. The overall positive rate of respiratory viruses was 28.07% (112/399) with HRV accounting for most at 9.52% (38/399). Thirty-seven VP4/VP2 sequences were successfully obtained from the 38 HRV-positive specimens. Three genotypes involving 25 serotypes were identified with 13 strains belonging to HRV-A, 14 belonging to HRV-B, and 10 belonging to HRV-C. The three genotypes of HRV showed alternate prevalence or co-prevalence.Conclusions:HRV was the main pathogen causing URTI in adult patients in Nanjing from October 2021 to September 2022, and three genotypes of HRV-A, B and C were prevalent alternatively or together.

Protective Effects of Zhi Ciweipi Water Extracts on Dextran Sulfate Sodium Salt⁃Induced Ulcerative Colitis in Mice / 中国生物化学与分子生物学报

Ulcerative colitis (UC) is a disease characterized by chronic inflammation of the intestinal mucosa. However, its exact pathogenesis is not fully understood. Zhi Ciweipi (ZCWP), as a traditional Chinese medicine (TCM), has demonstrated suitable anti-inflammatory effects in the treatment of patients with bloody stool and hemorrhoids. However, its therapeutic effects on ulcerative colitis have yet to be investigated in depth. The aim of this study was to investigate the protective effect of the aqueous extract of ZCWP against dextran sulfate sodium salt (DSS)-induced ulcerative colitis in mice and its possible mechanism of action. Successful simulation of ulcerative colitis was achieved by providing mice with drinking water containing 3% DSS. The HE staining results revealed that the aqueous extract of ZCWP could significantly reduce DSS-induced colonic injuries. Transcriptome sequencing analysis identified 10 key inflammation-related genes (IL⁃6, IL⁃1β, CSF2, TNF, IL10, IFN⁃γ, CXCL1, CXCL2, CXCL9, CXCL10), all of which were significantly downregulated (P<0. 05) in response to treatment with the aqueous extract of ZCWP according to qRT-PCR and Western blotting analyses. The immunofluorescence results further indicated that the aqueous extract of ZCWP was able to reduce the DSS-induced increase in the proportion of M1-type macrophages in the colon. Using single-cell sequencing, we thoroughly investigated the signaling relationships between different cell types, which revealed particularly strong communication between M1-type macrophages and fibroblasts. Subsequent qRT-PCR and Western blot analyses verified that the aqueous extract of ZCWP significantly downregulated the expression of DSS-induced fibrosis-related genes in colonic tissues (P<0. 05). In conclusion, the results of this study suggest that the aqueous extract of prepared ZCWP exerts a protective effect against DSS-induced ulcerative colitis by inhibiting M1-type macrophage polarization, downregulating the expression of inflammatory factors, and preventing strong communication between M1-type macrophages and fibroblasts. These findings not only reveal the therapeutic mechanism by which ZCWP aqueous extract treats colitis, but also provide a new theoretical basis for its application in clinical practice.

Effect of HCMV infection on immune reconstitution of CD8+T cells in children with allogeneic hematopoietic stem cell transplantation / 中华预防医学杂志

Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.

Effect of HCMV infection on immune reconstitution of CD8+T cells in children with allogeneic hematopoietic stem cell transplantation / 中华预防医学杂志

Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.

Cholesterol paradox in the community-living old adults: is higher better? / 老年心脏病学杂志（英文版）

OBJECTIVE@#To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.@*METHODS@#A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators.@*RESULTS@#A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death.@*CONCLUSIONS@#In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Comparison of clinical and immunological characteristics between primary Sjögren's syndrome patients with positive and negative anti-SSB antibody / 北京大学学报(医学版)

OBJECTIVE@#To analyze the differences of clinical manifestations and laboratory features between primary Sjögren's syndrome (pSS) patients with positive and negative anti-Sjögren's syndrome type B (SSB) antibody.@*METHODS@#The clinical data of pSS patients hospitalized in Department of Rheumato-logy and Immunology, Peking University Third Hospital were retrospectively analyzed to investigate the differences of clinical and laboratory features between anti-SSB positive and negative groups. The t test, Mann-Whitney U test, Chi-square test and Fisher's exact probability were used for analysis.@*RESULTS@#A total of 142 pSS patients were enrolled in this study, including 137 females and 5 males with a mean age of (54.8±13.3) years. The anti-SSB positive group included 44 patients accounting for 31.0% of the pSS patients. The anti-SSB positive pSS patients were younger at disease onset and at visit [age at visit: (50.9±14.5) years vs. (56.5±12.4) years; age at onset: (42.2±14.8) years vs. (49.5±15.3) years, P < 0.05]. The patients with anti-SSB positive more frequently presented with rash (29.5% vs. 14.3%, P < 0.05), enlargement of parotid glands (27.3% vs. 8.2%, P < 0.05), renal tubular acidosis (15.9% vs. 4.2%, P < 0.05), immune thrombocytopenia (9.1% vs. 1.0%, P < 0.05), rheumatoid factor (RF) positive (85.0% vs. 49.4%, P < 0.05), higher RF and antinuclear antibody (ANA) titers (median: 89.8 IU/mL vs. 20.5 IU/mL; median: 320 vs. 160, P < 0.05), anti-Sjögren's syndrome type A (SSA) antibody positive (97.7% vs. 64.3%, P < 0.05), elevation of γ globulin (71.4% vs. 38.5%, P < 0.05), higher levels of IgG (median: 21.0 g/L vs. 15.6 g/L, P < 0.05), higher proportions of CD3-CD19+ cells [(21.0±11.9)% vs. (13.7±9.6)%, P < 0.05] and lower proportions of CD3+ cells [(67.2±14.4)% vs. (76.6%±13.1)%, P < 0.05] than those negative. However, the anti-SSB positive group was less likely to show anti-mitochondrial antibodies (AMA)-M2 positivity (10.5% vs. 35.6%, P < 0.05). Glucocorticoids (90.9% vs. 73.5%, P < 0.05) and immunosuppressants (54.5% vs. 36.7%, P < 0.05) were more frequently used in anti-SSB positive pSS patients than those negative.@*CONCLUSION@#The anti-SSB positive pSS patients were younger at disease onset while more frequently presenting with various symptoms, higher levels of other antibodies and activation of B cells than those negative. Glucocorticoids and immunosuppressants were more frequently used, indicating that anti-SSB positive group presented with a more severe clinal phenotype.