Functional constipation （FC） is a common functional disorder of the intestines， mainly characterized by reduced bowel movement frequency， difficulty in defecation， a sensation of incomplete evacuation， and hard stools， which severely affect patients’ quality of life. Research indicates that the pathogenesis of FC is closely related to gut microbiota dysbiosis and abnormal bile acid secretion. Bile acids， as endogenous natural laxatives， promote bowel movements by enhancing colonic secretion and regulating intestinal motility； meanwhile， gut microbiota influence colonic transit function by regulating the enteric nervous system， immune system， and their metabolic products. Based on an overview of the relationship between gut microbiota and bile acid metabolism， this article systematically reviews the current research status on the mechanisms of traditional Chinese medicine （TCM） in treating FC by regulating the balance of the gut microbiota-bile acid axis. It is found that single Chinese medicinal herbs （such as Atractylodes macrocephala）， isolated compounds （such as Platycodon grandiflorum polysaccharides）， herbal formulas （such as Shanger huang pill）， acupuncture， and moxibustion can up-regulate the abundance of beneficial bacteria， reshape the microbial structure， correct bile acid metabolism， and activate the Takeda G-protein receptor 5/farnesoid X receptor pathway to treat FC.

Objective:This study aims to establish an early warning diagnosis model for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and to provide a simple, rapid, and accurate auxiliary diagnosis basis for clinical practice.Methods:The sample bank of subjects (patients admitted to the Eighth Medical Center of the PLA General Hospital from September 10, 2021, to July 25, 2023) was constructed, including the model establishment cohort [SCOPD group 49, 42 males and 7 females, (69.71±11.16) years old; AECOPD group 53, 49 males and 4 females, (72.60±10.19) years old] and the model validation cohort [SCOPD group 35, 28 males and 7 females, (69.97±10.40) years old; AECOPD group 35, 33 males and 2 females, (71.43±9.67) years old]. Fasting peripheral blood samples were collected, and the expression levels of IL-5, IL-17A, and IFN-α were detected by flow cytometry. Different expression levels were analyzed by Mann-Whitney U test. Binary logistic regression analysis was used to screen the related risk factors of COPD patients in acute exacerbation. The diagnostic efficacy of the model was evaluated by the receiver operating characteristic (ROC) curve.Results:The levels of IL-5 [1.64 (0.60, 2.86) pg/ml], IL-17A [1.42 (0.88, 2.29) pg/ml], and IFN-α [0.91 (0.59, 1.81) pg/ml] in the SCOPD group were significantly decreased compared with the AECOPD group IL-5 [4.68 (2.34, 9.40) pg/ml, Z=-5.033, P<0.001], IL-17A [2.33 (1.59, 4.62) pg/ml, Z=-3.919, P<0.001], IFN-α [2.83 (0.91, 3.75) pg/ml, Z=-4.127, P<0.01] in the cohort of model establishment. The results of binary logistic regression analysis between SCOPD and AECOPD groups showed that IL-5, IL-17A, and IFN-α were independent risk factors for acute exacerbation of patients with COPD ( P<0.05). And the regression equation is Y=-2.861+0.364×IL-5+0.385×IL-17A+0.445×IFN-α. The AUC value of IL-5, IL-17A, IFN-α and combined detection was 0.866 ( P<0.001). Compared to the SCOPD group and the AECOPD group in the cohort of model validation, the receiver operating characteristic (ROC) curve showed that the combined model of three (AUC=0.858, P<0.001) could be used to diagnose the AECOPD. And the Kappa value was 0.773( P<0.05). Conclusion:The combined detection of IL-5, IL-17A, and IFN-α has high diagnostic efficacy for patients with acute exacerbation of COPD. This method provides a new potential tool for the clinical diagnosis of AECOPD and has the value of further exploration and optimization, promotion, and application.

Objective:To explore effect of Glioma-associated oncogene family zinc finger 1(GLI1)on hypoxia induced trans-formation of NR8383 to M1 phenotype and development of pulmonary hypertension(PH).Methods:Fifteen adult male Wistar rats were randomly divided into control group,hypoxia PH model group and hypoxic PH with GANT61 treatment group,with 5 rats in each group.PH related indexes of rats were detected by small animal ultrasound and right cardiac catheter experiment to determine effect of GLI1 specific inhibitor GANT61 on progression of PH.Pulmonary arterial thickness was measured by HE staining.α-SMA and M1 polarization markers TNF-α and IL-1β expressions were determined by immunohistochemistry.M1 polarization markers CD86 and TNF-α expressions were determined by immunofluorescence.GLI1 expression and NF-κB protein were detected by Western blot.mRNA expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 were detected by qRT-PCR.CHIP-PCR verified that GLI1 regulates NF-κB promoter activity.IL-12 content was detected by ELISA.Rat pulmonary artery smooth muscle cells proliferation was detected by CCK-8.Results:GLI1 inhibitor GANT61 could alleviate symptoms of PH in hypoxic rats(P<0.05).Compared with hypoxic group,inhibition of GLI1 reduced expressions of TNF-α and IL-1β in rat lung tissue(P<0.05).In cell experiments,hypoxia induced M1 polarization of NR8383 by up-regulating GLI1 to activate NF-κB pathway,GLI1 overexpression increased expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 in M1 macrophages(P<0.05).NR8383 culture supernatants could stimulate pulmonary artery smooth muscle cell proliferation(P<0.05)and contribute to development of PH.Conclusion:Hypoxia activates NF-κB pathway by up-regulating GLI1 to induce M1 polarization of macrophages contributes to development of PH.

Objective To explore the application value of lymphocyte subsets combined with various cytokines in the disease progression of elderly patients with corona virus disease 2019(COVID-19).Methods From December 2022 to January 2023,146 elderly patients with COVID-19 diagnosed in the emergency ward of the Eighth Medical Center of PLA General Hospital were selected and divided into two groups according to the prognosis:127 cases in the COVID-19 survival group,19 cases in the COVID-19 death group.In addition,51 osteoporosis patients in geriatric medicine department were collected as control group.The proportion and absolute count of lymphocyte subsets(including T,B and NK cells),and 12 cytokines in plasma(including IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,TNF-α and IFN-γ)were compared between the control group and COVID-19 group,survival group and death group.The receiver operating characteristic(ROC)curve was used to evaluate its prognostic value in elderly patients with COVID-19 infection.Results Compared with the control group:① The proportion of NK cells in COVID-19 group was decreased,while the proportion of B cells was increased,and the differences were statistically significant(Z=-3.386,-4.140,all P<0.01).There was no significant difference in the proportion of T,CD8+T and CD4+T cells,and the differences were not statistically significant(Z=-1.244,-1.770,-0.951,all P>0.05).② The absolute numbers of T,CD8+T,CD4+T,NK and B cells in COVID-19 group were decreased,and the differences were statistically significant(Z=-9.418～-6.539,all P<0.01).③ The concentrations of IL-2,IL-6,IL-1β,IFN-γ,IL-8,IL-17,IL-12P70 and IL-10 in COVID-19 group were all increased,and the differences were statistically significant(Z=-8.851～-1.986,all P<0.05).There was no significant difference in the concentrations of IL-5,IFN-α,TNF-α and IL-4,and the differences were not statistically significant(Z=-0.460～-0.217,all P>0.05).Compared with the survival group:① There was no significant difference in the proportion of T,CD8+T,CD4+T,NK and B cells in the death group(Z=-1.873～-0.422,all P>0.05).② The absolute numbers of T,CD8+T and CD4+T cells in the death group were all decreased,and the differences were statistically significant(Z=-2.667,-2.287,-2.556,all P<0.05),while there was no significant difference in absolute numbers of NK and B cellsm and the differences were not statistically significant(Z=-1.934,-0.532,all P>0.05).③ The concentrations of IL-6,IFN-γ,IL-8,IL-17 and IL-10 in the death group were all increased,and the differences were not statistically significant(Z=-4.211～-2.655,all P<0.05),and there was no significant difference in the concentrations of IL-5,IFN-α,IL-2,IL-1β,IL-12p70,TNF-α and IL-4 the differences were not statistically significant(Z=-1.329～-0.279,all P>0.05).ROC curve analysis for the prognostic value of lymphocyte subsets combined with cytokines in elderly patients with COVID-19 showed that:the areas of total T cells,B cells and NK cells under ROC curve for predicting the prognosis of COVID-19 infection were 0.94,0.80 and 0.93,respectively.The areas of CD4+T cells and CD8+T cells under ROC curve for predicting the prognosis of COVID-19 infection were 0.93 and 0.90,respectively.The areas of IL-6,IFN-γ,IL-8,IL-17 and IL-10 in cytokines under the ROC curve for predicting the prognosis of COVID-19 infection were 0.91,0.71,0.87,0.74 and 0.90,respectively.However,the area of combined lymphocyte subsets and cytokines under ROC curve for predicting the prognosis of COVID-19 infection reached 0.99.Conclusion The immune status of elderly patients with COVID-19 was generally low.Evaluation of immune status has important clinical guidance significance in disease diagnosis,disease observation and prognosis.

Etiological research is necessary for understanding the occurrence and epidemiological patterns of diseases, and is also a prerequisite for the diagnosis, prevention and treatment of clinical diseases. Mendelian randomization(MR), a method of research that combines genetics and epidemiology, has the advantage of exploring the causal relationship between exposure and disease genetically as well as avoiding confounding factors and reverse causation. Thus, it has been extensively utilized in the etiological study of diseases. This paper reviews the implementation of MR in the research of ocular diseases and provides ideas and approaches for the investigation of related mechanisms as well as the development of intervention strategies.

【Objective】 To investigate the current status of incision sites to obtain intact specimens in laparoscopic nephrectomy by urologists in China, so as to provide reference for the standardized procedure. 【Methods】 During Jun.20, 2021 and Jul.4, 2021, more than 20 000 urologists in a WeChat group were surveyed with a questionnaire. The general data, incision sites and related complications were statistically analyzed. 【Results】 A total of 601 valid questionnaires were collected, covering urologists from 31 provinces, autonomous regions and municipalities. Surgical approaches: 68 urologists chose trans-abdominal approach, 432 chose posterior abdominal space approach, 101 chose both surgical approaches. Incision sites: 97 urologists chose lumbar transverse incision, 202 chose dorsal oblique incision of the waist, 119 chose ventral oblique incision, 93 chose the paramedian incision, 112 chose the lower abdominal oblique incision (Gibson), 11 chose the transverse lower abdominal incision (Pfannenstiel), 7 chose the median incision of the lower abdomen, 2 chose the median incision in the upper abdomen, 15 chose axillary midline direct incision; 399 chose to cut off the muscles, and 202 chose not to. Complications: 232 urologists reported pain after 2 weeks, 369 reported no pain; 325 reported numbness after 2 weeks, 276 reported no numbness; 66 reported incisional hernia, 535 reported no hernia. 【Conclusions】 Chinese urologists tend to choose retroperitoneoscopic nephrectomy and waist incision to obtain intact specimens. Transperitoneal laparoscopic nephrectomy has a variety of incisions for intact specimens. There is no standardized incision sites to obtain intact specimens.

Objective:To investigate the regulatory effects of mitofusin 1 (MFN1) on lipopolysaccharide (LPS)-induced Raw264.7 mouse macrophages pyroptosis and to provide reference for further study on the prevention of inflammation and fibrosis caused by macrophage dysfunction.Methods:Raw264.7 mouse macrophages were cultured in vitro and used to construct a model of LPS-induced pyroptosis. CCK-8 staining, PI staining, LDH release assay and Western blot were used to verify the Raw264.7 pyroptosis induced by LPS. MFN1 expression was detected by Western blot. DCFH-DA probe was used to detect the synthesis of total reactive oxygen species (ROS); Mito-SOX was used to detect mitochondrial ROS; JC-1 mitochondrial membrane potential was detected by fluorescence probe to reflect mitochondrial damage. Based on Ubibrowser database, it was predicted that MFN1 could bind to a variety of E3 ubiquitin ligases. Then, immunofluorescence and co-immunoprecipitation (CO-IP) were used to analyze MFN1 ubiquitination. An overexpression plasmid for MFN1 was constructed and transfected into Raw264.7 cells to detect the changes in pyroptosis and mitochondrial function. Results:LPS could induce the pyroptosis of Raw264.7 cells and mitochondrial dysfunction. MFN1 expression was decreased after LPS stimulation. Ubiquitinated MFN1 was detected by CO-IP. Ubiquitination inhibitor MG-132 inhibited LPS-induced expression of pyroptosis-related proteins including NLRP3, Pro-caspase-1, Caspase-1, IL-1β and IL-18 and improved mitochondrial function. MFN1 overexpression relieved the mitochondrial dysfunction and pyroptosis of Raw264.7 cells induced by LPS.Conclusions:The ubiquitination of MFN1 induced by LPS was involved in mitochondrial dysfunction and macrophage pyroptosis, suggesting that MFN1 was a potential target for the treatment of macrophage-induced inflammation and related diseases.

Objective:To evaluate a self-designed intelligent robot-assisted minimally invasive reduction system in the reduction of unstable pelvic fractures by a cadaveric anatomic study.Methods:Ten unembalmed cadavers (7 male and 3 female ones) were used in this study. In each cadaveric specimen an unstable pelvic fracture was created in accordance with clinical case models (3 cases of type B1, 4 cases of type B2 and 3 cases of type C1 by the Tile classification). A self-designed intelligent robot-assisted minimally invasive reduction system was used to assist the reduction in the cadaveric models. Intraoperative registration and navigation time, autonomous reduction time, total operation time and reduction error were measured.Results:Effective reduction was completed in 10 bone models with the assistance of our self-designed intelligent robot-assisted minimally invasive reduction system. The time for intraoperative registration and navigation averaged 47.4 min (from 32 to 74 min), the autonomous reduction time 73.9 min (from 48 to 96 min), and the total operation time 121.3 min (from 83 to 170 min). The reduction error averaged 2.02 mm (from 1.67 to 2.62 mm), and the reduction results met the clinical requirements.Conclusion:Our self-designed intelligent robot-assisted minimally invasive reduction system is a new clinical solution for unstable pelvic fractures, showing advantages of agreement with clinical operative procedures, high reduction accuracy and operational feasibility, and reduced radiation exposure compared to a conventional operation.

Objectives To study the clinical characteristics,diagnosis,treatment and prognosis of cancer metastases to the thyroid gland.Methods At Tianjin Medical University Cancer Hospital,from 1980 to 2016 30 patients were identified with a metastatic malignant tumor of the thyroid gland.Results Primary tumor sites were in the esophagus (26.7％),lung (16.7％),and kidney (13.3％).The median age at discovery of thyroid metastasis was 56 years old.The time lapse ranged from 0 to 108 months.There were 18 patients with metachronous metastasis with median survival of 36 months,12 patients were with synchronous metastasis,and the median survival was 8 months (P ＜ 0.01).20 patients were treated with thyroid surgery,and of which 15 patients were given post-op radiotherapy and chemotherapy.Patients who underwent thyroid resection had a median survival of 15 months,while that was 8 months in those without thyoid surgery (P ＜ 0.01).Conclusions Metastases to the thyroid gland is a rare clinical phenomenon,the prognosis of patients is mainly related to the biological behavior of primary tumors,but surgical resection and combined treatment can increase the survival rate.

Objective To investigate the effect of sub-anesthesia dose of isoflurane in 60％ oxygen on acute lung injury in aged rats with sepsis.Methods Ninety male Sprague-Dawley rats,aged 12-14 months,weighing 500-800 g,were divided into 3 groups (n=30 each) using a random number table:sham operation group (Sham group),sepsis group (S group),and sepsis plus isoflurane plus oxygen treatment group (S+I+O group).Sepsis was induced by cecal ligation and puncture in S and S+I+O groups.In group S+I+O,0.7％ isoflurane in 60％ oxygen was inhaled for 1 h starting from 1 and 6 h after operation.Eighteen rats were selected in each group and observed for 7 days after operation,and the survival rate was recorded.Six rats were selected in each group at 24 h after operation,and bronchoalveolar lavage fluid (BALF) was collected to determine the protein concentrations (by BCA protein assay),blood samples were collected from the femoral artery for blood gas analysis,PaO2 was recorded,and the oxygenation index was calculated.Six rats in each group were sacrificed at 24 h after operation,the left lung specimens were obtained and stained with hematoxylin and eosin for examination of pathological changes,the right lung specimens were obtained for determination of wet to dry weight ratio (W/D ratio),and blood samples were collected from the right atrium for measurement of the concentrations of interleukin-1β (IL-1β),IL-6,tumor necrosis factor-α (TNF-α),high-mobility group box 1 protein (HMGB1) and IL-10 in serum (by enzyme-linked immunosorbent assay).Results Compared with group Sham,the survival rate was significantly decreased,and the concentrations of IL-1β,IL-6,TNF-α,HMGB1 and IL-10 in serum were increased in S and S+I+O groups,and W/D ratio and protein concentrations in BALF were significantly increased,and the oxygenation index was decreased in group S (P＜0.05).Compared with group S,the survival rate was significantly increased,W/D ratio and protein concentrations in BALF were decreased,the oxygenation index was increased,the concentrations of IL-1β,IL-6,TNF-α and HMGB1 in serum were decreased,and the concentration of serum IL-10 was increased (P＜0.05),and the pathological changes were significantly attenuated in group S+I+O.Conclusion Sub-anesthesia dose of isoflurane in 60％ oxygen can reduce acute lung injury in aged rats with sepsis,and the mechanism may be ralated to inhibiting systemic inflammatory responses.