An novel effective and safe model for the diagnosis of nonalcoholic fatty liver disease in China: gene excavations, clinical validations, and mechanism elucidation.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. NAFLD leads to liver fibrosis and hepatocellular carcinoma, and it also has systemic effects associated with metabolic diseases, cardiovascular diseases, chronic kidney disease, and malignant tumors. Therefore, it is important to diagnose NAFLD early to prevent these adverse effects. METHODS: The GSE89632 dataset was downloaded from the Gene Expression Omnibus database, and then the optimal genes were screened from the data cohort using lasso and Support Vector Machine Recursive Feature Elimination (SVM-RFE). The ROC values of the optimal genes for the diagnosis of NAFLD were calculated. The relationship between optimal genes and immune cells was determined using the DECONVOLUTION algorithm CIBERSORT. Finally, the specificity and sensitivity of the diagnostic genes were verified by detecting the expression of the diagnostic genes in blood samples from 320 NAFLD patients and liver samples from 12 mice. RESULTS: Through machine learning we identified FOSB, GPAT3, RGCC and RNF43 were the key diagnostic genes for NAFLD, and they were further demonstrated by a receiver operating characteristic curve analysis. We found that the combined diagnosis of the four genes identified NAFLD samples well from normal samples (AUC = 0.997). FOSB, GPAT3, RGCC and RNF43 were strongly associated with immune cell infiltration. We also experimentally examined the expression of these genes in NAFLD patients and NAFLD mice, and the results showed that these genes are highly specific and sensitive. CONCLUSIONS: Data from both clinical and animal studies demonstrate the high sensitivity, specificity and safety of FOSB, GPAT3, RGCC and RNF43 for the diagnosis of NAFLD. The relationship between diagnostic key genes and immune cell infiltration may help to understand the development of NAFLD. The study was reviewed and approved by Ethics Committee of Tianjin Second People's Hospital in 2021 (ChiCTR1900024415).

Hedan tablet ameliorated non-alcoholic steatohepatitis by moderating NF-κB and lipid metabolism-related pathways via regulating hepatic metabolites.

Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease. If not treated, it can lead to liver damage, cirrhosis and even liver cancer. However, advances in treatment have remained relatively slow, and there is thus an urgent need to develop appropriate treatments. Hedan tablet (HDP) is used to treat metabolic syndrome. However, scientific understanding of the therapeutic effect of HDP on NASH remains limited. We used HDP to treat a methionine/choline-deficient diet-induced model of NASH in rats to elucidate the therapeutic effects of HDP on liver injury. In addition, we used untargeted metabolomics to investigate the effects of HDP on metabolites in liver of NASH rats, and further validated its effects on inflammation and lipid metabolism following screening for potential target pathways. HDP had considerable therapeutic, anti-oxidant, and anti-inflammatory effects on NASH. HDP could also alter the hepatic metabolites changed by NASH. Moreover, HDP considerable moderated NF-κB and lipid metabolism-related pathways. The present study found that HDP had remarkable therapeutic effects in NASH rats. The therapeutic efficacy of HDP in NASH mainly associated with regulation of NF-κB and lipid metabolism-related pathways via arachidonic acid metabolism, glycine-serine-threonine metabolism, as well as steroid hormone biosynthesis.

Multicentre, parallel, open-label, two-arm, randomised controlled trial on the prognosis of electrical impedance tomography-guided versus low PEEP/FiO2 table-guided PEEP setting: a trial protocol.

INTRODUCTION: Previous studies suggested that electrical impedance tomography (EIT) has the potential to guide positive end-expiratory pressure (PEEP) titration via quantifying the alveolar collapse and overdistension. The aim of this trial is to compare the effect of EIT-guided PEEP and acute respiratory distress syndrome (ARDS) network low PEEP/fraction of inspired oxygen (FiO2) table strategy on mortality and other clinical outcomes in patients with ARDS. METHODS: This is a parallel, two-arm, multicentre, randomised, controlled trial, conducted in China. All patients with ARDS under mechanical ventilation admitted to the intensive care unit will be screened for eligibility. The enrolled patients are stratified by the aetiology (pulmonary/extrapulmonary) and partial pressure of arterial oxygen/FiO2 (≥150 mm Hg or <150 mm Hg) and randomised into the intervention group or the control group. The intervention group will receive recruitment manoeuvre and EIT-guided PEEP titration. The EIT-guided PEEP will be set for at least 12 hours after titration. The control group will not receive recruitment manoeuvre routinely and the PEEP will be set according to the lower PEEP/FiO2 table proposed by the ARDS Network. The primary outcome is 28-day survival. ANALYSIS: Qualitative data will be analysed using the χ2 test or Fisher's exact test, quantitative data will be analysed using independent samples t-test or Mann-Whitney U test. Kaplan-Meier analysis with log-rank test will be used to evaluate the 28-day survival rate between two groups. All outcomes will be analysed based on the intention-to-treat principle. ETHICS AND DISSEMINATION: The trial is approved by the Institutional Research and Ethics Committee of the Peking Union Medical College Hospital. Data will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05307913.

YIQIFUMAI INJECTION AMELIORATED SEPSIS-INDUCED CARDIOMYOPATHY BY INHIBITION OF FERROPTOSIS VIA XCT/GPX4 AXIS.

ABSTRACT: Sepsis-induced cardiomyopathy ( SIC ) is a distinct form of myocardial injury that disrupts tissue perfusion and stands as the significant cause of mortality among sepsis patients. Currently, effective preventive or treatment strategies for SIC are lacking. YiQiFuMai injection (YQFM), composed of Panax ginseng C.A. Mey., Ophiopogon japonicus (Thunb.) Ker Gawl., and Schisandra chinensis (Turcz.) Baill., is widely used in China to treat cardiovascular diseases, such as coronary heart disease, heart failure, and SIC . Research has shown that YQFM can improve cardiac function and alleviate heart failure through multiple pathways. Nevertheless, the mechanisms through which YQFM exerts its effects on SIC remain to be fully elucidated. In this study, we firstly investigated the therapeutic effects of YQFM on a SIC rat model and explored its effects on myocardial ferroptosis in vivo. Then, LPS-induced myocardial cell death model was used to evaluate the effects of YQFM on ferroptosis and xCT/GPX4 axis in vitro . Furthermore, using GPX4 inhibitors, we aimed to verify whether YQFM improved cardiomyocyte ferroptosis through the xCT/GPX4 axis. The results showed that YQFM was effective in alleviating myocardial injury in septic model rats. Besides, the concentrations of iron and the levels of lipid peroxidation-related factors (ROS, MDA, and 4-HNE) were significantly decreased and the expression of xCT/GPX4 axis was upregulated in SIC rats after YQFM treatment. In vitro studies also showed that YQFM alleviated iron overload and lipid peroxidation and activated xCT/GPX4 axis in LPS-induced myocardial cell death model. Moreover, GPX4 inhibitor could abolish the effects above. In summary, the study highlights the regulatory effect of YQFM in mitigating myocardial injury. It probably achieves this ameliorative effect by enhancing xCT/GPX4 axis and further reducing ferroptosis.

Cellular senescence contributes to mechanical ventilation-induced diaphragm dysfunction by upregulating p53 signalling pathways.

BACKGROUND: Mechanical ventilation can cause acute atrophy and injury in the diaphragm, which are related to adverse clinical results. However, the underlying mechanisms of ventilation-induced diaphragm dysfunction (VIDD) have not been well elucidated. The current study aimed to explore the role of cellular senescence in VIDD. METHODS: A total of twelve New Zealand rabbits were randomly divided into 2 groups: (1) spontaneously breathing anaesthetized animals (the CON group) and (2) mechanically ventilated animals (for 48 h) in V-ACV mode (the MV group). Respiratory parameters were collected during ventilation. Diaphragm were collected for further analyses. RESULTS: Compared to those in the CON group, the percentage and density of sarcomere disruption in the MV group were much higher (p < 0.001, both). The mRNA expression of MAFbx and MuRF1 was upregulated in the MV group (p = 0.003 and p = 0.006, respectively). Compared to that in the CON group, the expression of MAFbx and MuRF1 detected by western blotting was also upregulated (p = 0.02 and p = 0.03, respectively). Moreover, RNA-seq showed that genes associated with senescence were remarkably enriched in the MV group. The mRNA expression of related genes was further verified by q-PCR (Pai1: p = 0.009; MMP9: p = 0.008). Transverse cross-sections of diaphragm myofibrils in the MV group showed more intensive positive staining of SA-ßGal than those in the CON group. p53-p21 axis signalling was elevated in the MV group. The mRNA expression of p53 and p21 was significantly upregulated (p = 0.02 and p = 0.05, respectively). The western blot results also showed upregulation of p53 and p21 protein expression (p = 0.03 and p = 0.05, respectively). Moreover, the p21-positive staining in immunofluorescence and immunohistochemistry in the MV group was much more intense than that in the CON group (p < 0.001, both). CONCLUSIONS: In a rabbit model, we demonstrated that mechanical ventilation in A/C mode for 48 h can still significantly induce ultrastructural damage and atrophy of the diaphragm. Moreover, p53-dependent senescence might play a role in mechanical ventilation-induced dysfunction. These findings might provide novel therapeutic targets for VIDD.

Therapeutic effects of paeoniflorin on irritable bowel syndrome in rats.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional bowel disorder (FBD). OBJECTIVES: To assess the therapeutic effects of paeoniflorin (PF) on IBS in rats. METHOD: Sixty male Sprague-Dawley rats were randomly divided into normal, model, positive drug, low-dose PF, medium-dose PF and high-dose PF groups (n = 10). After gavage for 2 consecutive weeks, the effect of PF on abdominal pain symptoms was assessed based on the abdominal withdrawal reflex (AWR) score, fecal water content and pathological changes in colon tissues. D-lactate, interleukin-1ß (IL-1ß), transforming growth factor-ß (TGF-ß) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay, and phosphorylated nuclear factor kappa B (p-NF-κB) p65 was detected by Western blotting. The abundance and diversity changes of intestinal flora were explored using 16S ribosomal RNA sequencing. RESULT: In PF groups, the mucosal morphology of colon tissues was intact, and the glands were arranged neatly and structured clearly, without obvious inflammatory cell infiltration. Compared with the model group, PF groups had significantly elevated pain threshold, and mRNA and protein levels of zonula occludens-1 (ZO-1) and occludin, decreased AWR score at 20 mmHg pressure, fecal water content, mRNA levels of IL-1ß, TGF-ß, and TNF-α, protein level of p-NF-κB p65 and level of serum D-lactate, and reduced levels of serum IL-1ß, TGF-ß, and TNF-α (p < 0.05, p < 0.01). PF groups had higher abundance of Lactobacillus, Akkermansia, Alistipes, and Bacteroides, but lower abundance of Desulfovibrio, Parasutterella, and Enterococcus than those of the model group. CONCLUSIONS: PF exerts therapeutic effects on IBS in rats probably by regulating the intestinal flora, and then up-regulating the expressions of ZO-1 and occludin in colon tissue while down-regulating the levels of IL-1ß, TGF-ß, TNF-α, D-lactate and p-NF-κB p65.

PEEP application during mechanical ventilation contributes to fibrosis in the diaphragm.

BACKGROUND: Positive end-expiratory airway pressure (PEEP) is a potent component of management for patients receiving mechanical ventilation (MV). However, PEEP may cause the development of diaphragm remodeling, making it difficult for patients to be weaned from MV. The current study aimed to explore the role of PEEP in VIDD. METHODS: Eighteen adult male New Zealand rabbits were divided into three groups at random: nonventilated animals (the CON group), animals with volume-assist/control mode without/ with PEEP 8 cmH2O (the MV group/ the MV + PEEP group) for 48 h with mechanical ventilation. Ventilator parameters and diaphragm were collected during the experiment for further analysis. RESULTS: There was no difference among the three groups in arterial blood gas and the diaphragmatic excursion during the experiment. The tidal volume, respiratory rate and minute ventilation were similar in MV + PEEP group and MV group. Airway peak pressure in MV + PEEP group was significantly higher than that in MV group (p < 0.001), and mechanical power was significantly higher (p < 0.001). RNA-seq showed that genes associated with fibrosis were enriched in the MV + PEEP group. This results were further confirmed on mRNA expression. As shown by Masson's trichrome staining, there was more collagen fiber in the MV + PEEP group than that in the MV group (p = 0.001). Sirius red staining showed more positive staining of total collagen fibers and type I/III fibers in the MV + PEEP group (p = 0.001; p = 0.001). The western blot results also showed upregulation of collagen types 1A1, III, 6A1 and 6A2 in the MV + PEEP group compared to the MV group (p < 0.001, all). Moreover, the positive immunofluorescence of COL III in the MV + PEEP group was more intense (p = 0.003). Furthermore, the expression of TGF-ß1, one of the most potent fibrogenic factors, was upregulated at both the mRNA and protein levels in the MV + PEEP group (mRNA: p = 0.03; protein: p = 0.04). CONCLUSIONS: We demonstrated that PEEP application for 48 h in mechanically ventilated rabbits will cause collagen deposition and fibrosis in the diaphragm. Moreover, activation of the TGF-ß1 signaling pathway and myofibroblast differentiation may be the potential mechanism of this diaphragmatic fibrosis. These findings might provide novel therapeutic targets for PEEP application-induced diaphragm dysfunction.

Epidemiological characteristics of pertussis in Yiwu City / 预防医学

Objective @#To investigate the epidemiological and clinical characteristics of cases with pertussis in Yiwu City, Zhejiang Province, so as to provide insights into pertussis diagnosis and control.@*Methods@#A total of 186 patients with definitive diagnosis of pertussis in medical institutions in Yiwu City from November 1, 2020 to August 31, 2022 were recruited, and subjects' demographic, clinical symptoms and history of pertussis vaccination were collected using questionnaire surveys. The temporal, population, and spatial distribution and clinical symptoms of pertussis were analyzed using a descriptive epidemiological method, and the clinical characteristics of pertussis patients with different doses of pertussis vaccination were compared.@*Results@#Pertussis was found to predominantly occur during the period between July and November (101 cases, 54.30%), and the three highest-incidence regions included Jiangdong Street, Beiyuan Street and Choujiang Street (87 cases, 46.77%). The 186 pertussis cases included 105 males (56.45%) and 81 females (43.55%), and included 144 cases with age of onset under 7 year (77.42%). Preschool and diaspora children were predominant among all pertussis cases, and the main clinical symptoms included spasmodic cough (97 cases, 52.15%), post-tussive vomiting (82 cases, 44.09%) and aggravated cough at night (77 cases, 41.40%). Routine blood tests measured 119 cases with abnormal white blood cell counts (63.98%), 137 cases with abnormal lymphocyte counts (73.66%), 39 cases with abnormal neutrophil counts (20.97%), 21 cases with abnormal platelet counts (11.29%) and 111 cases with abnormal hemoglobin concentrations (59.68%). There were 55 cases that were unvaccinated (29.57%), 23 cases that were not fully vaccinated (12.37%), and 108 cases that were fully vaccinated (58.06%). There were significant differences among pertussis cases with different doses of vaccination in terms of age, incidence of post-tussive vomiting, percentage of abnormal platelet counts and percentage of hemoglobin concentrations (all P<0.05).@*Conclusions@#The majority of pertussis cases are preschool and diaspora children in Yiwu City from November 1, 2020 to August 31, 2022, and the clinical symptoms mainly include spasmodic cough, post-tussive vomiting and aggravated cough at night, with atypical symptoms. The capability for differential diagnosis of pertussis is required to be improved in medical institutions.

Er-Chen Decoction Alleviates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Rats through Remodeling Gut Microbiota and Regulating the Serum Metabolism.

Many studies have found that the dysfunction in gut microbiota and the metabolic dysfunction can promote nonalcoholic fatty liver disease (NAFLD) development. Er-Chen decoction (EC) can be used in the treatment of NAFLD. However, the mechanism of this hepatoprotection is still unknown. In this study, we constructed a rat model with NAFLD fed with high-fat chow and administered EC treatment. The therapeutic effects of EC on NAFLD were evaluated by measuring transaminases, blood lipid levels, and pathological changes in the liver. In addition, we measured the effects of EC on liver inflammatory response and oxidative stress. The changes in gut microbiota after EC treatment were studied using 16S rRNA sequencing. Serum untargeted metabolomics analysis was also used to study the metabolic regulatory mechanisms of EC on NAFLD. The results showed that EC decreased the serum transaminases and lipid levels and improved the pathological changes in NAFLD rats. Furthermore, EC enhanced the activities of SOD and GSH-Px and decreased MDA level in the liver. EC treatment also decreased the gene and protein levels of IL-6, IL-1ß, and TNF-α in the liver and serum. The 16S rRNA sequencing and untargeted metabolomics indicated that EC treatment affected the gut microbiota and regulated serum metabolism. Correlation analysis showed that the effects of EC on taurine and hypotaurine metabolism, cysteine and methionine metabolism, and vitamin B6 metabolism pathways were associated with affecting in the abundance of Lactobacillus, Dubosiella, Lachnospiraceae, Desulfovibri, Romboutsia, Akkermansia, Intestinimonas, and Candidatus_saccharimonas in the gut. In conclusion, our study confirmed the protective effect of EC on NAFLD. EC could treat NAFLD by inhibiting oxidative stress, reducing inflammatory responses, and improving the dysbiosis of gut microbiota and the modulation of the taurine and hypotaurine metabolism, cysteine and methionine metabolism, and vitamin B6 metabolism pathways in serum.

Effect of Jiangan-Jiangzhi Pill on Gut Microbiota and Chronic Inflammatory Response in Rats with Non-Alcoholic Fatty Liver.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with high rates of occurrence. Research has found that NAFLD patients experience varying degrees of intestinal flora imbalance. There is evidence that traditional Chinese medicine (TCM) positively regulates imbalances in the gut microbiota caused by liver diseases. Jiangan-Jiangzhi pill (JGJZ) is a common Chinese remedy that can treat NAFLD clinically. This article investigates how JGJZ affects NAFLD and assesses related changes in the intestinal flora. We established a NAFLD rat model by feeding them a high-fat diet (HFD) and gave different interventions. After twelve weeks, the results revealed that JGJZ decreased the total cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase in the serum of NAFLD rats. Histopathological staining demonstrated that JGJZ relieved cellular fat accumulation in the liver. Inflammatory cytokine levels (IL-6, IL-1ß, and TNF-α) were down-regulated. Analysis of 16S rRNA demonstrated that JGJZ changed the community compositional structure of gut microbiota, characterized by a decrease in the Firmicutes-to-Bacteroidetes ratio, and increased gut microbiota diversity and the abundance of dominant groups. Accordingly, our study illustrated that JGJZ exerted a better effect in treating HFD-induced NAFLD, which may be closely related to ameliorating gut microbiota dysbiosis.

Development and validation of the nomogram based on INR and eGFR for estimation of mortality in patients with acute-on-chronic hepatitis B liver failure.

AIMS AND OBJECTIVES: Acute-on-chronic hepatitis B liver failure (ACHBLF) is a critical clinical syndrome with a high short-term mortality evolved from chronic hepatitis B (CHB)-related liver disease. Prediction of mortality risk and early intervention can improve the prognosis of patients. This study aimed to develop and validate the nomogram for short-time mortality estimation in ACHBLF patients defined according to Asian Pacific Association for the Study of the Liver (APASL). METHODS: A study of 105 ACHBLF patients with 90-day follow up was performed to develop the nomogram. Patients were randomly assigned to derivation cohort (n = 75) and validation cohort (n = 35) according to 7:3. Concordance index (C-index), calibration curve and decision curve analysis (DCA) were used to evaluate the nomogram. We also compared the nomogram with APASL ACLF research consortium (AARC) score, model for end-stage liver disease (MELD) score, MELD with serum sodium (MELD-Na) score and albumin-bilirubin (ALBI) score. The nomogram was validated using an external cohort including 40 patients. RESULTS: The 28-day and 90-day mortality of 105 patients were respectively 49.52% and 55.24%. Albumin (ALB), international normalized ratio (INR) and estimated glomerular filtration rate (eGFR) were independent predictors for 28-day mortality; INR and eGFR were independent predictors for 90-day mortality. C-index of Nomogram-1 for 28-day mortality and Nomogram-2 for 90-day mortality were respectively 0.82 and 0.81. Calibration curve and Hosmer-Lemeshow test (Nomogram-1, 0.323; Nomogram-2, 0.231) showed optimal agreement between observed and predicted death. Areas under receiver operator characteristic curve(AUROC) of Nomogram-1(0.772) and Nomogram-2(0.771) were larger compared with AARC, MELD, MELD-Na and ALBI score. The results were well estimated in the external validation cohort. CONCLUSIONS: This study highlighted the predictive value of eGFR, and the nomogram based on INR and eGFR could effectively estimate individualized risk for short-term mortality of ACHBLF patients defined according to APASL.

Traditional Chinese Medicine Ganshuang Granules Attenuate CCl4 -Induced Hepatic Fibrosis by Modulating Gut Microbiota.

Gut dysbiosis contributes to hepatic fibrosis. Emerging evidence revealed the major role of traditional Chinese medicine (TCM) in gut microbiota homeostasis. Here, we aimed to investigate the anti-fibrotic activity and underlying mechanism of ganshuang granules (GS), particularly regarding gut microbiota homeostasis. CCl4 -induced hepatic fibrosis models were allocated into 4 groups receiving normal saline (model), 1.0, 2.0, or 4.0 g/kg GS for 5 weeks. As result, GS treatment alleviated liver injury in CCl4 -induced hepatic fibrosis, presenting as decreases of the liver index, alanine aminotransferase, and aspartate transaminase. Histological staining and expression revealed that the enhanced oxidative stress, inflammatory and hepatic fibrosis in CCl4 -induced models were attenuated by GS. Immunohistochemical staining showed that tight junction-associated proteins in intestinal mucosa were up-regulated by GS. 16S rRNA sequencing showed that GS rebalanced the gut dysbiosis manifested as improving alpha and beta diversity of gut microbiota, reducing the ratio of Firmicutes to Bacteroidetes, and regulating the relative abundance of various bacteria. In summary, GS decreased the intestinal permeability and rebalanced the gut microbiota to reduce the oxidative stress and inflammation, eventually attenuating CCl4 -induced hepatic fibrosis.

Nano-Gold PCR in Detection of TERT Methylation and Its Correlation with Hepatitis B-Related Hepatocellular Carcinoma.

This study aimed to introduce nano-gold PCR for detection of TERT methylation, and explore the correlation between TERT methylation and prognosis of hepatocellular carcinoma (HCC). From March 2016 to March 2018, 154 HBV carriers treated in our hospital were enrolled in the study and divided into HCC (68 cases), cirrhosis (45 cases) and chronic hepatitis (CH) groups (41 cases) based on clinical disease. HCC patients were further divided into methylation (30 cases) and non-methylation (38 cases) subgroup based on methylation status of the TERT. TERT methylation of HCC specimens were 44.12% and 35.24% by nano-PCR and conventional PCR, respectively. The TERT methylation and TERT expression in HCC specimens were higher than for cirrhosis and CH specimens. A significant positive correlation was observed between TERT methylation and TERT expression. AFP, Edmondson classification, tumor size, hilar lymph node and intrahepatic metastasis, and TNM staging in the methylation group were higher than in non-methylation group. Further, overall survival and progression-free survival were significantly shorter. Nano-gold PCR is more sensitive in detecting TERT methylation. As CHB progresses, TERT methylation increases. Greater methylation of the gene is associated with worse prognosis in HCC patients.

[Comparison of femoral tunnel and early curative effect analysis between arthroscopic three approach and traditional anteromedial portal for reconstruction of anterior cruciate ligament].

OBJECTIVE: To study the three-approach and traditional anterior medial technique to establish the femoral tunnel of position, length, and coronal angle and the early efficacy of anterior cruciate ligament reconstruction. METHODS: Through retrospective research, from December 2018 to June 2019, a total of 36 patients diagnosed with simple anterior cruciate ligament tear and undergoing surgery were collected. All patients had a clear history of knee sprains and were divided into two groups. A group of 16 patients, including 11 males and 5 females, with an average age of (30.13±6.54) years and an injury time of 7 to 60 (30.19±15.78) days, three-approach technique was used to drill the femoral tunnel to reconstruct the anterior cruciate ligament. Another group of 20patients, including 15 males and 5 females, with an average age of (30.80±8.60) years, and an injury time of 7 to 60 (27.35±15.50) days, the traditional anterior medial approach was used to drill the femoral tunnel to reconstruct anterior cruciate ligament. CT 3D reconstruction technique was used to evaluate the femoral tunnel and the knee joint function was evaluated by Lysholm score of the knee joint. RESULTS: All patients achieved primary healing after the surgical incision. No femoral tunnel fracture, vascular and nerve damage, difficulty in graft passage during the operation, and venous thrombosis occurred. All 36 patients were followed up on an outpatient basis, with a follow up period of 9 to 15 (12.00±2.83) months. Three-dimensional CT reconstruction was used to evaluate the femoral tunnel of the patients. The position of the femoral tunnel was described using the quartile method as the three-approach group:the lower (27.83±1.97) % of the femoral condyle and the posterior (25.57±3.20) %;the traditional approach group:the lower (28.38±3.21) % of the femoral condyle and the posterior (26.23±3.20) %. Bone tunnel length, three-approach group:(35.20±5.52) mm in total length, (23.20±2.07) mm in thick bone tunnel;traditional approach group:(34.60±4.26) mm in total length, (22.56±2.50) mm in thick bone tunnel. Coronal plane angle, three-approach group:(47.93±5.98) °;traditional approach group:(41.78±6.62) °. Knee joint Lysholm score, three-approach group:48.67±4.18 before surgery;97.00±2.48 at last follow up;traditional approach group:49.75±5.33 before surgery, 97.30±2.68 at last follow up, there were significant differences before and after surgery, no significant statistical difference between two groups. CONCLUSION: The positions of the femoral tunnel drilled by the two methods were within the range of the anatomic stop of the anterior cruciate ligament, and there was no statistical difference. Compared with the traditional anterior medial approach, the coronal plane angle of the femoral tunnel drilled by the three-approach approach is relatively large, and there were no statistical differences in the length of the tunnel, the early postoperative effect of the two surgical methods, and the operation time. But the three approach has a wider and clearer vision. In addition, the knee flexion angle required for drilling the femoral tunnel during surgery is significantly smaller than that of traditional approach technology, which reduces the difficulty of surgery.

Health seeking behavior and associated factors among individuals with cough in Yiwu, China: a population-based study.

BACKGROUND: Previous studies have shown that a certain proportion of the population did not seek medical treatment after coughing, and understanding the potential reasons is crucial for disease prevention and control. METHOD: A population-based study was conducted with the probability proportional to population size sampling in Yiwu, Zhejiang, China. A total of 5855 individuals aged ≥15 years lived in Yiwu for more than 6 months were included. All participants completed a laptop-based questionnaire to collect detailed information by a face-to-face interview. Characteristics of individuals were described by categories of health seeking behavior using frequency and percentage. Univariate and multivariate logistic regression analyses were performed to estimate the associations of social-demographic and cough characteristics with health seeking behavior. RESULTS: 19.3% (1129/5855) of participants had a cough in the past month, 40% (452/1129) had sought medical treatment. Of these, 26.5% (120/452) chose hospitals at county level or above. Individuals aged ≥65 years old (OR = 2.25, 95% CI: 1.23, 4.12), female (OR = 1.57, 95% CI: 1.21, 2.06), living in rural areas (OR = 1.30, 95% CI: 1.003, 1.69), persistent cough for 3-8 weeks (OR = 2.91, 95% CI: 1.72, 4.92) and with more accompanying symptoms (P trend < 0.001) were more likely to seek medical treatment, but those coughed for > 8 weeks were not (p > 0.5). Female (OR = 0.33, 95% CI: 0.21, 0.54) and people living in rural areas (OR = 0.57, 95% CI: 0.36, 0.92) were less likely to choose hospitals at county level or above while the higher educated were more likely to (OR = 3.29, 95% CI: 1.35, 8.02). Those who coughed for more than 2 weeks were more likely to choose hospitals at or above the county level. But the number of accompanying symptoms does not show any significant relationship with the choice of medical facility. CONCLUSION: The present study found that age, sex, living areas and features of cough were associated with health seeking behavior. It is worth noting that those who coughed for too long (e.g. > 8 weeks) were less likely to seek medical treatment. Targeted measures should be developed based on the key factors found in this study to guide persons to seek medical treatment more scientifically.

Kang-Xian Pills Inhibit Inflammatory Response and Decrease Gut Permeability to Treat Carbon Tetrachloride-Induced Chronic Hepatic Injury through Modulating Gut Microbiota.

Kang-Xian (KX) pills have been clinically used for the treatment of chronic hepatic injury (CHI). However, the mechanisms of KX on CHI remain unknown. The aim of this study mainly focused on the anti-inflammatory effects of KX in a CHI mouse model based on modulating gut microbiota and gut permeability. We first established a CHI model using carbon tetrachloride (CCl4) and treated it with KX. The anti-inflammatory effects of KX on CHI model mice and the changes in gut permeability after KX treatment were also investigated. 16S rRNA analysis was used to study the changes of gut microbiota composition after KX treatment. In addition, gut microbiota was depleted using a combination of antibiotics in order to further confirm that KX could inhibit the inflammatory response and decrease gut permeability to treat CHI by modulating the gut microbiota. Results showed that KX treatment significantly improved liver function in CHI model mice. KX could also increase the levels of tight junction proteins in the colon and decrease the expression of proinflammatory cytokines in the liver. 16S rRNA analysis indicated that KX treatment affected the alpha and beta diversities in CHI model mice. Further analysis of 16S rRNA sequencing indicated that KX treatment increased the ratio of Firmicutes to Bacteroidetes at the phylum level. At the genus level, KX treatment increased the relative abundance of Lactobacillus, Bacteroides, and Akkermansia and decreased the relative abundance of Ralstonia, Alloprevotella, and Lachnoclostridium. However, KX could not alleviate CHI after depleting the gut microbiota. The effects of KX on gut permeability and inflammatory response in the liver were also decreased following the depletion of gut microbiota. In conclusion, our current study demonstrated that gut microbiota was significantly affected during CHI progression. KX could inhibit the inflammatory response and decrease the gut permeability in CHI model mice through modulating the gut microbiota.

[Value of a new predictive model in evaluating short-term prognosis of patients with hepatitis B virus related acute-on-chronic liver failure].

OBJECTIVE: To establish a predictive model and investigate its value in evaluating short-term prognosis of patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF). METHODS: Patients with HBV-ACLF admitted to Tianjin Second People's Hospital and Beijing Youan Hospital, Capital Medical University from May 2015 to October 2018 were enrolled. The data of gender, age, laboratory markers at admission, model for end-stage liver disease (MELD) score and clinical complications were collected for analysis. According to the prognosis on 12-week, patients were divided into survival group and death group. Univariate analysis and binary Logistic regression analysis were used to test the risk factors for short-term prognosis of the patients with HBV-ACLF, and a prediction model was established. The accuracy of each index and the established model were verified by the receiver operating characteristic (ROC) curve. RESULTS: A total of 148 patients with HBV-ACLF were enrolled in the study, 91 cases survived while 57 cases died during the 12-week period. The age, total bilirubin (TBIL), neutrophil percentage (NEUT%), hepatitis B surface antigen (HBsAg), MELD score of death group were higher than those of survival group [age (years old): 50.00 (44.50, 55.00) vs. 43.00 (34.00, 53.00), TBIL (µmol/L): 310.30 (240.70, 405.70) vs. 266.40 (184.20, 360.20), NEUT%: (74.52±13.05)% vs. (66.64±12.35)%, lgHBsAg (kU/L): 3.72 (3.29, 3.92) vs. 2.97 (2.49, 3.78), MELD score: 24.27 (19.71, 27.40) vs. 21.88 (18.83, 24.38), all P < 0.05], while albumin (ALB), total cholesterol (CHO), prothrombin activity (PTA) and alpha-fetoprotein (AFP) were lower than those of survival group [ALB (g/L): 29.80 (27.05, 31.05) vs. 30.80 (28.00, 33.90), CHO (mmol/L): 1.98 (1.50, 2.38) vs. 2.49 (2.05, 3.01), PTA: (30.37±7.09)% vs. (32.94±6.03)%, AFP (µg/L): 21.54 (9.28, 51.54) vs. 66.16 (24.50, 152.80), all P < 0.05]. Logistic regression analysis showed that NEUT%, HBsAg and AFP were independent risk factors for short-term prognosis of patients with HBV-ACLF [odds ratio (OR) was 77.843, 1.439, 0.995, respectively, all P < 0.05]. According to the results of regression analysis, the NHA-ACLF model (NEUT%+HBsAg+AFP) was established. The formula was logit (NHA-ACLF) = -5.441+5.688×NEUT%+0.430×lgHBsAg-0.005×AFP. The area under the ROC curve (AUC) of the NHA-ACLF model for pred HBV-ACLF patients was 0.790, which was better than NEUT% (AUC = 0.696), lgHBsAg (AUC = 0.670), AFP (AUC = 0.703) and MELD score (AUC = 0.640). When the cut-off value of NHA-ACLF model score was 0.459, the sensitivity was 73.7%, and the specificity was 79.1%. CONCLUSIONS: NEUT%, HBsAg and AFP are independent predictive indicator for short-term prognosis in patients with HBV-ACLF. Compared with MELD score, the risk assessment model NHA-ACLF has a greater value in predicting the short-term prognosis of patients with HBV-ACLF.

Composition of "gold juice" using an ancient method based on intestinal microecology.

OBJECTIVE: To identify potentially effective bacterial components of gold juice, a traditional Chinese medicine treatment used for fecal microbiota transplantation. METHODS: Fecal samples were collected from five healthy children (two boys and three girls; mean age, 7.52 ± 2.31 years). The children had no history of antibiotic use or intestinal microecological preparation in the preceding 3 months. Fresh fecal samples were collected from children to prepare gold juice in mid-to-late November, in accordance with traditional Chinese medicine methods, then used within 7 days. Finally, 16S rDNA sequence analysis was used to identify potentially effective bacterial components of gold juice. QIIME software was used for comparisons of microbial species among gold juice, diluent, filtrate, and loess samples. RESULTS: Microflora of gold juice exhibited considerable changes following "ancient method" processing. Microbial components significantly differed between gold juice and filtrate samples. The gold juice analyzed in our study consisted of microbes that synthesize carbohydrates and amino acids by degrading substances, whereas the filtrate contained probiotic flora, Bacteroides, and Prevotella 9. CONCLUSIONS: This study of microbial components in gold juice and filtrate provided evidence regarding effective bacterial components in gold juice, which may aid in clinical decisions concerning fecal microbiota transplantation.

[Study on the application value of MELD-Na, CLIF-C OFs, COSSH-ACLFs and NLR scoring systems in patients with hepatitis B virus related acute-on-chronic liver failure].

OBJECTIVE: To verify the accuracy of the model for end-stage liver disease-sodium (MELD-Na), chronic liver failure consortium organ failure score (CLIF-C OFs), Chinese Group on the Study of Severe Hepatitis B-Acute-on-chronic Liver Failure score (COSSH-ACLFs) and neutrophil-to-lymphocyte ratio (NLR) scoring systems in patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) and to explore its value in clinical application. METHODS: The clinical data (gender, age, disease stage) and laboratory indicators [alanine transferase (ALT), glutamate transaminase (AST), total bilirubin (TBil), albumin (ALB), blood urea nitrogen (BUN), creatinine (Cr), serum sodium (Na), prothrombin activity (PTA), international standardized ratio (INR), neutrophils count (NEU) and lymphocytes count (LYM)] of 163 patients with HBV-ACLF from July 2010 to July 2018 in Tianjin Second People's Hospital were retrospectively analyzed. After 8 weeks of admission, the patients were divided into death group (90 cases) and survival group (73 cases) according to survival status. The MELD-Na, CLIF-C OFs, COSSH-ACLFs scores and NLR of death group and survival group were compared, and a multivariate Logistic regression analysis was used to analyze the independent risk factors for HBV-ACLF. Propensity score analysis was used to demonstrate the accuracy of the method and receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of the independent risk factors. RESULTS: There were no significant differences in gender, disease stage, ALB, BUN, Cr, Na, NEU on admission between the two groups (all P > 0.05). The age [years old: 43.00 (34.00, 53.00) vs. 50.00 (42.50, 55.00)] and serum levels of ALT [U/L: 252.90 (61.43, 613.33) vs. 359.10 (115.15, 784.70)], AST [U/L: 146.15 (90.88, 449.30) vs. 237.80 (109.00, 635.05)], TBil [µmol/L: 265.10 (183.10, 347.60) vs. 307.50 (229.90, 405.55)] and INR [2.13 (1.91, 2.46) vs. 2.29 (2.02, 2.94)] in survival group were lower than those in death group and the PTA [%: 34.00 (28.00, 38.00) vs. 31.00 (24.00, 36.00)] and LYM [×109/L: 1.37 (0.72, 1.79) vs. 0.85 (0.51, 1.39)] levels were significantly higher than those in death group (both P < 0.05). The MELD-Na [17.99 (16.60, 19.63) vs. 19.16 (17.43, 20.80)], CLIF-C OFs [9.00 (8.00, 9.00) vs. 9.00 (9.00, 10.00)], COSSH-ACLFs [4.87 (4.63, 5.48) vs. 5.47 (5.07, 5.80)] and NLR [2.86 (2.21, 5.19) vs. 4.38 (2.54, 8.46)] were lower in survival group than those of the death group (all P < 0.05). Logistic regression analysis showed that CLIF-C OFs [odds ratio (OR) = 0.532, 95% confidence interval (95%CI) was 0.380-0.744, P < 0.05] and NLR (OR = 0.901, 95%CI was 0.835-0.972, P < 0.05) were the independent risk factors for the prognosis of HBV-ACLF. After propensity score matching, the data of 59 cases in each group were successfully matched, there were no significant differences in age, gender, disease stage, ALT, AST, TBil, ALB, BUN, Cr, Na, PTA, INR and NEU between the two groups (all P > 0.05), and statistically significant difference in the baseline LYM [×109/L: 1.35 (0.74, 1.73) vs. 0.81 (0.51, 1.30)] were found between the survival group and the death group. The CLIF-C OFs, COSSH-ACLFs scores and NLR were lower in survival group compared with those of the death group [CLIF-C OFs: 9.00 (8.00, 9.00) vs. 9.00 (8.00, 10.00), COSSH-ACLFs: 4.99 (4.69, 5.64) vs. 5.34 (5.03, 5.81), NLR: 2.85 (2.21, 5.72) vs. 4.38 (2.47, 10.20), all P < 0.05] and CLIF-C OFs (OR = 0.593, 95%CI was 0.401-0.878, P < 0.05) and NLR (OR = 0.593, 95%CI was 0.401-0.878, P < 0.05) were still as the independent risk factors for the prognosis of HBV-ACLF. The sensitivity of CLIF-C OFs ≥ 9 and NLR ≥ 3.14 to forecast the 8-week clinical outcome of HBV-ACLF patients were 76.7% and 67.1%, the specificity were 48.9% and 56.7%, and AUC were 0.662 and 0.623. CLIF-C OFs was combined with NLR to increase the specificity of forecasting the 8-week clinical outcome of HBV-ACLF patients to 77.8%. CONCLUSIONS: CLIF-C OFs and NLR scores are independent risk factors affecting the clinical outcome of HBV-ACLF, and have better clinical value in predicting the prognosis of HBV-ACLF. Combined application of the two scores will be more beneficial to the prognosis of HBV-ACLF.