Risk factors of in-hospital death in severe pneumonia patients receiving enteral nutrition support / 中华临床营养杂志

Objective:The decline in nutritional status in patients with severe pneumonia may contribute to an increase in in-hospital mortality. Enteral nutrition support can improve the nutritional status of patients, and is relatively easy to manage, with low cost and fewer serious complications. On the other hand, adverse reactions such as gastric retention and gastric microbiota translocation may increase the incidence of nosocomial pneumonia and increase the uncertainty of patient prognosis. There is no predictive model for in-hospital death in severe pneumonia patients receiving enteral nutrition support. The objective of this study was to investigate the risk factors of in-hospital death in patients with severe pneumonia receiving enteral nutrition support and to establish a prognostic model for such patients.Methods:This was a single-center retrospective study. Patients with severe pneumonia who were hospitalized in Peking Union Medical College Hospital and received enteral nutrition support were included from January 1, 2015 to December 31, 2020. The primary endpoints were in-hospital mortality rate and unordered discharge rate. The independent risk factors were determined using univariate and multifactorial logistic regression analysis, the nomogram scoring model was constructed, and the decision curve analysis (DCA) was performed.Results:A total of 632 severe pneumonia patients who received enteral nutrition support were included. Patients were divided into death and survival groups according to the presence or absence of in-hospital death, and 24 parameters were found with significant differences between groups. Nine parameters were independent predictors of mortality, namely the duration of ventilator use, the presence of malignant hyperplasia diseases, the maximal levels of platelet and prothrombin during hospitalization, and the nadir levels of alanine aminotransferase, serum albumin, sodium, potassium, and blood glucose. Based on these variables, a risk prediction scoring model was established (ROC = 0.782; 95% CI: 0.744 to 0.819, concordance index: 0.772). Calibration curves, DCA, and clinical impact curve were plotted to evaluate the goodness of function, accuracy, and applicability of the predictive nomogram, using the training and test sets. Conclusion:This study summarized the clinical characteristics of patients with severe pneumonia receiving enteral nutrition support and developed a scoring model to identify risk factors and establish prognostic models.

GDF15 negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal squamous cell carcinoma / 医学前沿

Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.

AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

A cohort study of incidence of club drug abuse in men who have sex with men in Qingdao / 中华流行病学杂志

Objective: To understand and analyze the incidence of club drug abuse and influencing factors in men who have sex with men (MSM) in Qingdao, and provide reference for the AIDS prevention and intervention in this population. Methods: From March 2017 to July 31, 2022, MSM who did not abuse club drug were recruited by snowball sampling of MSM social organizations in Qingdao, a prospective cohort was established, and a follow-up survey was conducted every 6 months. The survey collected the information about the MSM's demographic characteristics, sexual characteristics, club drug abuse and others. The incidence of club drug abuse was the outcome dependent variable and the interval between the recruitment into the cohort and the incidence of club drug abuse was the time dependent variable. Cox regression analysis was conducted to identify the influencing factors for club drug abuse. Results: A total of 509 MSM were recruited at baseline survey, and 369 eligible MSM were enrolled in this cohort. A total of 62 MSM began to abuse club drug during the study period, and the cumulative follow-up time was 911.54 person-years, the incidence of club drug abuse was 6.80/100 person-years. All the club drug abusers shared drugs with others in the first club drug abuse, and 16.13% (10/62) had mix-use of club drugs. The multivariate Cox proportional risk regression analysis showed that being students (aHR=2.17, 95%CI: 1.15-4.10), receiving no HIV testing or receiving 1 HIV testing during past 6 months (aHR=4.57, 95%CI:1.80-11.60; aHR=5.15, 95%CI: 2.83-9.36), having sex only with regular sexual partners during past 6 months (aHR=4.75,95%CI:2.32-9.75), having more than 4 homosexual partners (aHR=1.70, 95%CI:1.01-2.87) and abuse of club drug of sexual partners during past 6 months (aHR=12.78, 95%CI:3.06-53.35) were significantly associated with club drug abuse in the MSM. Conclusions: The incidence of club drug abuse was at a high level in the MSM cohort in Qingdao, indicating a high risk for HIV infection. Being student, receiving less HIV testing, having sex only with regular sexual partners, having more homosexual partners and abuse of club drug of sexual partners during past 6 months were risk factors for the incidence of club drug abuse in the MSM. Targeted surveillance and intervention measures should be strengthened to reduce the risk of club drug abuse in MSM.

Potential short-term effects of tobacco control scheme under various application scenarios of tobacco control measures across the globe: a Meta-analysis / 中华流行病学杂志

Objective: based on summarizing the simulation and prediction of tobacco control measures across the globe and sorting out the various scenarios of tobacco control measures, the potential short-term effects of seven tobacco control measures in different scenarios were systematically analyzed. Methods: Until April 2022, PubMed, Embase, EconLit, PsychINFO, and CINAHL databases were used to retrieve literature about tobacco control measures simulation and prediction models across the globe. Inclusion and exclusion criteria were strictly followed. Meta-analysis for the potential short-term effects of seven tobacco control measures in different scenarios was performed using the R software. Results: A total of 22 papers covering 16 countries were selected. Five studies were conducted in the United States, three in Mexico, and two in Italy. There were all papers with the measures to tax increases, smoke-free air laws, and mass media campaigns, 21 papers with youth access restrictions, 20 with marketing restrictions, and 19 with cessation treatment programs and health warnings. The tax increases had diverse influences on the price elasticity of different age groups. The price elasticity in the age group 15-17 years was the highest, which was 0.044 (95%CI: 0.038-0.051). The potential short-term effects of smoke-free air laws in workplaces were higher than in restaurants and other indoor public places. The effects of youth access restrictions were greater in the age group <16 years than in the age group 16-17. The stronger the implementation of other measures, the greater the potential short-term effects. A comparison of seven tobacco control measures showed that the cessation treatment programs increase in cessation rate was the highest, 0.404 (95%CI: 0.357-0.456). The reduction in smoking rate and reduction in initiation rate of youth access restrictions strongly enforced and publicized was the highest in the age group <16 years, 0.292 (95%CI: 0.269-0.315), and 0.292 (95%CI: 0.270-0.316). Conclusions: The potential short-term effects of seven tobacco control measures in different scenarios were evaluated more accurately and objectively through Meta-analysis. In the short term, cessation treatment programs will substantially increase smoking cessation rates, and strong youth access enforcement will sharply reduce smoking and initiation rates among adolescents under 16. These results also offer strong data-related support for the simulation and prediction of tobacco control measures in China and other countries.

Clinical Characteristics of 5 Cases of Immune Checkpoint Inhibitor Induced Diabetes Mellitus / 罕见病研究

  Objective  By summarizing the clinical characteristics and follow-up outcomes of 5 patients with immune checkpoint inhibitor induced diabetes mellitus (ICI-DM) and reviewing the relevant literatures, the article aims at providing reference to clinicians in the diagnosis and treatment of the ICI-DM.  Methods  Clinical data of 5 patients with ICI-DM who were admitted to Peking Union Medical College Hospital from December 2018 to February 2023 and did retrospectively analyzed.  Results  Five patients with a mean age of (65±7)years received treatment by the programmed cell death 1 (PD-1) or its ligand inhibitor (PD-L1). The median time from the first immunotherapy to the discovery of elevated plasma glucose was 100 (43, 210)days, and the median cycle of immunotherapy was 7 (2.5, 10.5). The onset of the illness of all the 5 patients started with diabetic ketosis or ketoacidosis. At the onset, urine ketone bodies were positive, random plasma glucose was (36.36±15.89)mmol/L, glycosylated hemoglobin A1c (HbA1c)was (8.6%±0.66%), arterial blood pH was (7.28±0.16), and the median fasting C-peptide level was 0.09 (0.05, 0.32)μg/L. Five patients had an onset plasma glucose level of grade 3 or 4.Then, ICI treatment was discontinued in all patients and insulin therapy started. The daily dosage of insulin was (56±20)IU, supplemented with hypoglycemic drugs. After treatment, urine ketone body turned negative, pH value increased to normal range, and random plasma glucose decreased significantly (the median difference of random blood glucose before and after treatment was 21.30 mmol/L, P=0.043) showing that the treatment was effective. During the follow-up, all patients continued to use insulin. The PD-1 or PD-L1 inhibitors were restarted after hyperglycemia remission. The tumor condition was under control.  Conclusions  ICI-DM mainly occurs in patients who receive treatment with PD-1 or PD-L1 inhibitors usually with acute hyperglycemia whose laboratory tests indicate insulin secretion defects. Some patients had positive islet cell antibodies, glutamic acid decarboxylase antibodies and autoantibodies.Patients with positive autoantibodies needed early diagnosis and continuous insulin treatment. ICI treatment can be restarted after endocrinologists brought the blood glucose under control.

A novel retrograde tibial nail for treatment of distal tibial fracture: preliminary results / 中华创伤骨科杂志

Objective:To investigate the effects of a novel retrograde tibial nail (RTN) in the treatment of distal tibial fractures.Methods:A retrospective study was conducted in the 11 patients with distal tibial fracture who had been admitted to Department of Traumatic Orthopedics, The Second Affiliated Hospital, Hengyang Medical School from July 2020 to July 2021. There were 5 male and 6 females, aged from 18 to 70 years (average 54.7 years). By the AO/OTA classification, there were 7 extra-articular distal fractures (3 cases of type 43-A1, 3 cases of type 43-A2 and one type 43-A3) and 4 intra-articular fractures (2 cases of type 43-C1 and 2 cases of type 43-C2); by the Gustilo classification, there were 7 closed fractures and 4 open fractures (2 cases of type I and 2 cases of type Ⅱ). All fractures were fixated with a novel RTN. Deformities like distal tibial varus and valgus as well as fracture-related complications were observed after operation while the curative effects evaluated by the ankle-hindfoot score of the American Orthopaedic Foot and Ankle Society (AOFAS).Results:This cohort was followed up for an average of 7.4 months (from 5 to 12 months). All patients obtained clinical union and recovered daily life and work. Radiographic evaluation showed no distal tibial varus or valgus. There were no such complications as postoperative infection, exposure of bone and internal fixation, compartment syndrome, or neurovascular lesion. According to the ankle-hindfoot score of AOFAS, 7 cases were excellent and 4 cases good.Conclusion:This novel retrograde tibial nail may result in good efficacy in the treatment of distal tibial fracture, but its advantages still need further verification.

Effect of liraglutide combined with metformin on weight loss in overweight or obese patients with type 2 diabetes and the influencing factors / 中华临床营养杂志

Objective:To investigate the efficacy and safety of liraglutide combined with metformin in the treatment of overweight or obese patients with type 2 diabetes, and to analyze the factors influencing the response to liraglutide.Methods:Seventy-three overweight or obese patients with well-controlled type 2 diabetes on metformin were selected and treated with liraglutide at 1.8 mg/d in addition to metformin at 1500 mg/d for 48 weeks. Relevant data were collected before and after treatment, including blood glucose, glycosylated hemoglobin (HbA1c), fasting insulin, serum lipid, body weight, waist circumference, hip circumference, body mass index (BMI), homeostatic model assessment for β-cell function (HOMA-β) and homeostatic model assessment for insulin resistance (HOMA-IR). Changes in metabolic markers, incidence of side effects, weight loss efficacy and corresponding influencing factors were evaluated.Results:After 48 weeks of treatment, fasting blood glucose, 2-hour postprandial blood glucose, HbA1c, fasting insulin, HOMA-IR, blood lipid, waist circumference, hip circumference and BMI decreased significantly compared with baseline ( P < 0.05). The most common side effects were tolerable gastrointestinal adverse events. The average weight loss after the initial 4-week treatment was 3.99 kg, accounting for 48.8% of the total weight loss, and then the change displayed a more subdued trend during the remaining treatment period. After the 48-week treatment, 73.1% and 34.6% of the patients lost more than 5% and 10% of body weight, respectively. Absolute weight loss was positively correlated with baseline weight and weight loss within the initial 4-week treatment was an independent predictor of weight loss ≥ 5% at the 48th week. Conclusions:Liraglutide combined with metformin is safe and effective in the treatment of overweight or obese patients with type 2 diabetes mellitus. Weight loss is significant during the initial 4 weeks and the early response seems to be a predictor for better long-term effect on weight loss.

MicroRNA-132 promotes atherosclerosis by inducing mitochondrial oxidative stressmediated ferroptosis / 南方医科大学学报

OBJECTIVE@#To explore the expression of microRNA-132 (miR-132) and its potential role in the development of atherosclerosis (AS).@*METHODS@#Thirty AS samples and 30 samples of normal peripheral vessels were collected from atherosclerotic patients undergoing peripheral angiostomy in our hospital for detecting the expression level of miR-132 using RT-qPCR. The expression of miR-132 in human umbilical vein endothelial cells (HUVEC) was up-regulated by liposome transfection, and intracellular reactive oxygen species (ROS), localization relationship between ROS and mitochondria, functional changes of mitochondrial reactive oxygen superoxide species (mtROS), mitochondrial membrane potential (MMP) and opening of mitochondrial permeability transition pore (mPTP) were analyzed by flow cytometry and laser confocal microscopy. The activity of mitochondrial redox respiratory chain complex (type I, II, III, IV and V) in HUVECs was detected using ELISA, and the expression levels of key iron death proteins were detected with Western blotting.@*RESULTS@#RT-qPCR results showed that miR-132 was significantly up-regulated in atherosclerotic plaques compared with normal vascular samples (P < 0.001). Compared with control HUVECs, HUVECs overexpressing miR-132 showed a significantly increased level of intracellular ROS (P < 0.001), and most of ROS was colocalized with mitochondria. HUVECs overexpressing miR-132 also showed significantly decreased MMP (P < 0.001) and obviously increased mtROS (P < 0.001) and opening of mPTP (P < 0.001), which led to mitochondrial REDOX respiratory chain stress disorder. The key iron death protein GPX4 was significantly down-regulated and the oxidized protein NOX4 was significantly increased in miR-132-overexpressing HUVECs (P < 0.001).@*CONCLUSION@#MiR-132 promotes atherosclerosis by inducing mitochondrial oxidative stress-mediated ferroptosis, which may serve as a promising therapeutic target for AS.

Survival analysis of unexpected small cell lung cancer following surgery / 中华肿瘤杂志

Objective: To investigate the survival and influencing factors of unexpected small cell lung cancer following surgery. Methods: We respectively reviewed the clinical characters of 104 patients who underwent surgical treatment and be proved as small cell lung cancer by pathology between January 2000 to October 2020 in Chinese PLA General Hospital. Overall survival (OS) of patients was evaluated using Kaplan-Meier and Cox proportional hazards analysis. Results: Of 104 patients, 27 cases showed central lesions, and other 77 showed peripheral nodules. The margin of nodules was smooth in 42 cases on CT imaging. The median OS was 34.3 months and 5-year OS rate was 45.8%. Postoperative 5-year OS rates for patients were 52.1%, 45.4%, and 27.8% for clinical stages Ⅰ, Ⅱ, and Ⅲ, respectively. Univariate analyses identified the age, surgical access, surgical approach, N stage, TNM stage and vascular cancer emboli were associated with OS (P<0.05). The N stage was an independent factor for the OS of patients (P<0.05). Conclusions: Patients with unexpected SCLC, including Ⅰ, Ⅱ and part ⅢA stage have favorable outcome and can benefit from surgery and systemic postoperative treatment. Standard lobectomy plus systemic lymph node dissection is commended.

Effect of Circular RNA hsa_circ_0067582 on the Proliferation and Invasion Ability of Gastric Cancer Cells / 中国医学科学院学报

Objective To investigate the effects on cell proliferation and invasion of the circular RNA hsa_circ_0067582 in gastric cancer(GC). Methods After hsa_circ_0067582 overexpression (Oe-circ_0067582) plasmid was transfected into AGS and SGC-7901 cells,the cell viability,proliferation,invasion ability,and apoptosis were detected by CCK-8,colony formation and EdU assays,Transwell assay,and flow cytometry,respectively.Western blotting was employed to detect the expression levels of proteins related to the cell apoptosis and epithelial-mesenchymal transition(EMT).The effect of Oe-circ_0067582 on the growth of SGC-7901 cells in nude mice was observed.Bioinformatics tools were used to predict the binding target miRNA of hsa_circ_0067582,and the competing endogenous RNA(ceRNA)regulatory network was established.Finally,functional enrichment was performed to analyze the biological functions of the target genes of the predicted miRNA. Results Compared with the pLO-ciR(empty plasmid)group,the Oe-circ_0067582 group in AGS and SGC-7901 cells attenuated the cell viability(t=7.883,P=0.001;t=5.679,P=0.005),proliferation(t=6.709,P=0.003;t=5.857,P=0.003),and invasion ability(t=7.782,P=0.002;t=6.342,P=0.003)and induced cell apoptosis(t=7.225,P=0.002;t=11.509,P=0.001).Western blotting showed that the Oe-circ_0067582 group in AGS and SGC-7901 cells up-regulated the protein levels of cysteinyl aspartate specific proteinase (Caspase) 3(t=6.863,P=0.002;t=7.024,P=0.001),Caspase 7(t=3.295,P=0.04;t=6.008,P=0.004),Caspase 9(t=4.408,P=0.012;t=6.278,P=0.004),and E-cadherin(t=12.453,P=0.002;t=10.867,P=0.001),while down-regulated those of Vimentin(t=7.242,P=0.002;t=5.694,P=0.004)and N-cadherin(t=6.480,P=0.003;t=7.446,P=0.001).Furthermore,Oe-circ_0067582 significantly inhibited the growth of tumor in the SGC-7901 tumor-bearing nude mice(t=3.526,P=0.017).The prediction based on TargetScan and miRnada suggested that hsa_circ_0067582 can competitively bind to hsa-miR-181b-3p,hsa-miR-337-3p,hsa-miR-421,and hsa-miR-548d-3p.The functional enrichment indicated that the target genes of miRNA were involved in multiple cancer-related biological processes including negative regulation of apoptotic process,gene expression,transcriptional misregulation in cancer,transforming growth factor-β,and p53 signaling pathways. Conclusion Oe-circ_0067582 can inhibit the proliferation and attenuate EMT process to reduce the invasion ability of AGS and SGC-7901 cells,which provides a new target for the treatment of GC.

Effect of moxibustion on M2 and P2X3 receptors of bladder tissue in rats with neurogenic bladder of detrusor areflexia after lumbar-sacral spinal cord injury / 中国针灸

OBJECTIVE@#To observe the effect of moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) on acetylcholine (Ach), adenosine triphosphate (ATP) and muscarinic-type choline receptor (M2) and purine receptor P2X3 in bladder tissue in the rats with neurogenic bladder (NB) of detrusor areflexia after lumbar-sacral spinal cord injury and explore the underlying mechanism of moxibustion for promoting detrusor contraction.@*METHODS@#Sixty SD rats were randomly divided into a model preparation group (n=45) and a sham-operation group (n=15). In the model preparation group, the modified Hassan Shaker spinal cord transection method was used to prepare the model of NB. In the sham-operation group, the spinal cord transection was not exerted except laminectomy and spinal cord exposure. Among the rats with successfully modeled, 30 rats were selected and divided randomly into a model group and a moxibustion group, with 15 rats in each one. On the 15th day after the operation, moxibustion was applied at "Guanyuan" (CV 4) and "Shenque" (CV 8) in the moxibustion group, 10 min at each acupoint, once a day. The consecutive 7-day treatment was as one course and the intervention for 2 courses was required. Urodynamic test was adopted to evaluate bladder function in rats. Using HE staining, the morphological changes in bladder tissue were observed. The content of Ach and ATP in bladder tissue was measured with biochemical method, and the protein and mRNA expression levels of M2 and P2X3 receptors in bladder tissue were detected with Western blot and real-time fluorescence quantification PCR method.@*RESULTS@#Compared with the sham-operation group, the maximum bladder capacity, leakage point pressure and bladder compliance were increased in the rats of the model group (P<0.05). Compared with the model group, the maximum bladder capacity, the leakage point pressure and bladder compliance were decreased in the rats of the moxibustion group (P<0.05). In the model group, the detrusor fibres were arranged irregularly, bladder epithelial tissues were not tightly connected and cell arrangement was disordered, combined with a large number of vacuolar cells. In the moxibustion group, compared with the model group, the detrusor fibres were arranged regularly, bladder epithelial cells were well distributed and vacuolar cells were reduced. Compared with the sham-operation group, the content of Ach and ATP in bladder tissue was decreased (P<0.05), the protein and mRNA expression levels of M2 and P2X3 receptors were reduced (P<0.05) in the model group. In the moxibustion group, the content of Ach and ATP in bladder tissue was increased (P<0.05) and the protein and mRNA expression levels of M2 and P2X3 receptors were increased (P<0.05) as compared with the model group.@*CONCLUSION@#Moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) may effectively improve bladder function in the rats with NB of detrusor areflexia after lumbar-sacral spinal cord injury and its underlying mechanism is related to promoting the release of Ach and up-regulating the expression of M2 receptor, thereby enhancing the release of ATP and increasing the expression of P2X3 receptor. Eventually, detrusor contraction is improved.

Indoleamine 2, 3-dioxygenase: An important medium with the role of a double-edged sword in various liver diseases / 临床肝胆病杂志

Indoleamine 2, 3-dioxygenase (IDO) is an important immunoregulatory enzyme, which can degrade the level of the mammalian essential amino acid tryptophan (TRP), catalyze the initiation and rate-limiting steps through the kynurenine pathway, and produce a variety of metabolites to participate in the immune response. On the one hand, IDO plays an immunosuppressive role in microenvironment and thus leads to infection and immune escape of tumor cells; on the other hand, IDO also exerts an inhibitory effect on the pathogens such as bacteria and parasites and thus protects the body from the harm of pathogens to a certain extent. Therefore, IDO is considered an important medium with the role of a double-edged sword in the development and progression of various liver diseases. This article reviews the latest research advances in IDO in viral hepatitis, liver fibrosis, liver cirrhosis, liver cancer, and hepatic echinococcosis.

Establishment of a trauma center improves therapeutic efficacy for patients with severe multiple injuries / 中华创伤骨科杂志

Objective:To investigate the effects of establishment of a trauma center on the therapeutic efficacy for patients with severe multiple injuries.Methods:A retrospective study was conducted in the patients who had been treated at The Second Affiliated Hospital, University of South China for severe multiple injuries from October 2015 to September 2019. They were assigned into 2 groups. The study group included 102 patients who had been treated after establishment of our trauma center (from October 2017 to September 2019) while the control group 126 patients who had been treated before establishment of our trauma center (from October 2015 to September 2017). The 2 groups were compared in terms of time for emergency treatment (from admission to emergency surgery or ICU), ICU stay, hospital stay, total medical costs and mortality.Results:There was a significant difference between the 2 groups in time for emergency treatment [51 (47, 57) min for the study group versus 97 (87, 107) min for the control group] ( P<0.05). There were no significant differences between the 2 groups in ICU stay [4 (1.8, 9.3) d versus 4 (2.0, 10.0) d], hospital stay [25.5 (15.8, 39.0) d versus 21.5 (12.8, 41.5) d], or total medical costs [￥41,259.0 yuan (￥26,950 yuan, ￥81,599 yuan)] ( P>0.05). There was a significant difference between the 2 groups in mortality [12.7% (13/102) for the study group versus 24.6% (31/126) for the control group] ( P<0.05). Conclusion:Establishment of a trauma center can effectively shorten time for emergency treatment, improve treatment efficacy and reduce mortality for patients with severe multiple injuries.

Genetic diversity of protopine-6-hydroxylase in three medicinal Papaver plants / 中国中药杂志

Sanguinarine is the main active component of the Papaver plants, and protopine-6-hydroxylase(P6 H), involved in the sanguinarine biosynthetic pathway, can oxidize protopine to 6-hydroxyprotopine. The investigation on the diversity of P6 H genes in the medicinal Papaver plants contributes to the acquirement of P6 H with high activity to increase the biosynthesis of sanguinarine. Five P6 H genes in P. somniferum, P. orientale, and P. rhoeas were discovered based on the re-sequencing data of the Papaver species, followed by bioinformatics analysis. With the elongation factor 1α(EF-1α), which exhibits stable expression in the root and stem, as the internal reference gene, the transcription levels of P6H genes in roots and stems of the Papaver plants were detected by real-time fluorescent quantitative PCR. As indicated by the re-sequencing results, there were two genotypes of P6H in P. somniferum and P. orientale, respectively, and only one in P. rhoeas. The bioinformatics analysis showed that the P6 H proteins of the three Papaver plants contained the conserved domain cl12078, which is the characteristic of p450 supergene family, and transmembrane regions. The existence of signal peptide remained verification. Real-time fluorescent quantitative PCR results revealed that the transcription level of P6 H in roots of P. somniferum was about 1.44 times of that in stems(α=0.05). The present study confirmed genetic diversity of P6 H in the three medicinal Papaver plants, which lays a basis for the research on the biosynthesis pathway and mechanism of sanguinarine in Papaver species.

Analysis of surgical strategy of percutaneous endoscopic lumbar discectomy in young and middle-aged double-segment patients with lumbar disc herniation / 北京大学学报(医学版)

OBJECTIVE@#To investigate clinical efficacy and safety of single and double segmental percutaneous lumbar discectomy for young and middle-aged patients with double-segment disc herniation.@*METHODS@#Retrospective analysis was undertaken for 32 young and middle-aged patients with percutaneous endoscopic lumbar discectomy (PELD) in the treatment of double-segment lumbar disc herniation from January 2015 to October 2018 in Peking University First Hospital. In the study, 18 cases were treated with single-segment treatment and 14 cases with double-segment treatment. Visual analogue score (VAS) and oswestry disability index (ODI) assessment were used to compare clinical symptom outcomes before surgery, 3 months after surgery and at the last follow-up. Macnab criteria were used to assess the patients' overall satisfaction after surgery. Imaging parameters included lumbar lordosis, intervertebral height at each segment and endplate angle of lesion segment on the X-ray. And Michigan State University(MSU) rating and Pfirrmann scoring system were used to evaluate the grade of disc herniation and disc degeneration respectively on magnetic resonance imaging (MRI). The perioperative parameters included the surgeon, anesthesia method, operation time, postoperative hospital stay, postoperative bracing time and perioperative complications.@*RESULTS@#The mean follow-up time was (26.78±10.64) months. There was no significant difference in the follow-up time and baseline information between the two groups(P > 0.05). ODI scores 3 months post-operatively and at the last follow-up were lower in the double segment (P < 0.05). The ODI improvement was also more significant in the double-segment group at the last follow-up (P < 0.05). There was no significant difference in radiographic parameters at baseline (P>0.05). MSU scale for the primary segment was significantly lowered after both operations (P < 0.05). MSU scale for secondary segment was significantly lowered in double segment group but not in single segment group. Other imaging parameters were similar between the two groups (P > 0.05). The operation time of the single-segment group was significantly shorter than that of the double-segment group(P < 0.001). No perioperative complications were found in either group, but three patients underwent secondary lumbar surgery during the postoperative follow-up period in the single-segment group.@*CONCLUSION@#For young and middle-aged patients with double-segment disc herniation, this study suggests double-segment PELD may be more advantageous than single-segment PELD in terms of asuring clinical efficacy without increasing perioperative risks.

Therapeutic effect of gene silencing peptidyl arginine deaminase 4 on pulmonary interstitial lesions induced by collagen-induced arthritis mice / 北京大学学报(医学版)

OBJECTIVE@#To investigate the therapeutic effect of gene silencing peptidyl arginine deaminase 4 (PAD4) on pulmonary interstitial lesions induced by collagen-induced arthritis (CIA) mice, and possible mechanisms.@*METHODS@#A CIA mouse model was established in DBA/1 mice, followed by a tail vein injection of the virus solution prepared by the PAD4-siRNA expression vector once a week for 8 times. The mice were sacrificed at the end of the experiment. The expression of PAD4 mRNA in lungs was detected by real-time quantitative PCR (qRT-PCR). The expression of PAD4 protein was detected by tissue immunohistochemistry. Cell culture was performed by spleen tissue. Flow cytometry changes in the ratio of Tfh cells to Tfr cells were examined; lung staining was performed in the lungs to observe changes in lung pathology.@*RESULTS@#(1) Compared with the blank group, the expression of PAD4 mRNA in the lung tissue of the model group increased, the difference was statistically significant (P < 0.05). PAD4 mRNA in the lung tissue of the CIA mice after PAD4-siRNA treatment. The expression level was significantly lower than that of the model group and the negative control group, and the difference was statistically significant (P < 0.05). (2) Red fluorescence was less in the lung tissue of the blank group, while more red fluorescence was observed in the inflammatory cell infiltration area and trachea around the lung tissue of the model group and the negative control group, and the red fluorescence of the three groups after PAD4-siRNA treatment was significantly reduced; (3) Compared with the blank group, the proportion of Tfh cells in the model group increased, the difference was statistically significant (P < 0.05), the proportion of Tfh cells in spleen cells of the CIA mice after PAD4-siRNA treatment was significantly lower than that of the model group and the negative control group, the difference was statistically significant (P < 0.05); compared with the blank group, in the mouse spleen cells in the model group the proportion of Tfr cells was slightly decreased, but the difference was not statistically signifi-cant. The proportion of Tfr cells in the spleen cells of the mice increased after PAD4-siRNA treatment, but the difference was statistically significant only in the PAD4-siRNA2 group compared with the model group and the negative control group (P < 0.05); (4) The proportion of Tfh/Tfr in the spleen cells of the model group was increased, compared with the blank group, the difference was statistically significant (P < 0.05); the ratio of Tfh/Tfr in the three groups after PAD4-siRNA treatment all decreased, the difference was statistically significant (P < 0.05); (5) Compared with the blank group, the alveolar wall of the lung tissue of the model group was thickened, the inflammatory cell infiltration was increased, and the lung tissue destruction and inflammatory infiltration of the CIA mice were decreased after PAD4-siRNA treatment. The degree of reduction was reduced.@*CONCLUSION@#Gene silencing of PAD4 can reduce the proportion of Tfh cells, increase the proportion of Tfr cells, reverse the proportion of Tfh/Tfr, and reduce the degree of interstitial lesions and inflammatory infiltration of lung tissue.

Chinese consensus on surgical treatment of traumatic rib fractures (2021) / 中华创伤杂志

Traumatic rib fractures are the most common injury in thoracic trauma. Previously，the patients with traumatic rib fractures were mostly treated non-surgically，of which 50%，especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities，being unable to retain a full-time job. In the past two decades，thanks to the development of internal fixation material technology，the surgical treatment of rib fractures has achieved good outcomes. However，there are still some problems in clinical treatment，including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans，and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore，the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association，in conjunction with national multidisciplinary experts，formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures（2021）following the principle of evidence-based medicine，scientific nature and practicality. This expert consensus puts forward some clear，applicable，and graded recommendations from aspects of preoperative imaging evaluation，surgical indications，timing of surgery，surgical methods，rib fracture sites for surgical fixation，internal fixation methods and material selections，treatment of combined injuries in rib fractures，in order to provide references for surgical treatment of traumatic rib fractures.

Microscope assisted anterior cervical discectomy and fusion for the treatment of single segment cervical spondylotic myelopathy / 中国骨伤

OBJECTIVE@#To compare the efficacy of microscope assisted anterior cervical discectomy and fusion with conventional surgical approach in the treatment of single-segment cervical spondylotic myelopathy.@*METHODS@#The clinical data of 89 patients with single-segment cervical spondylotic myelopathy treated from March 2015 to March 2019 were retrospectively analyzed. There were 55 males and 34 females, with an average of (52.00±11.36) years old. Among the patients, 34 cases were treated with conventional anterior cervical discectomy with fusion (conventional group), including C@*RESULTS@#Intraoperative blood loss and hospital stay in microscope group were less than those in conventional group (@*CONCLUSION@#Both methods can achieve satisfactory effect in treating single-segment cervical spondylotic myelopathy. However, microscope-assisted anterior cervical discectomy and fusion has advantages of clear vision, less bleeding and fewer intraoperative complications.

SNP of AHSA2 gene in three cattle breeds using snapshot technology

Droughtmaster is a tropical breed of beef cattle that can survive in hot climates and easily adapt to torrid environments. These traits are important in livestock breeding. In this study, we genotyped five single-nucleotide polymorphisms (SNPs) of the AHSA2 gene from 190 cattle belonging to three different breeds (Droughtmaster, Angus and Simmental) by using snapshot technology. This work aimed to identify the valuable molecular marker of heat resistance in cattle. Results showed that Droughtmaster exhibited higher expected heterozygosity and polymorphic information content compared with the two other breeds. The AHSA2-1 locus deviated from the Hardy– Weinberg equilibrium in the Droughtmaster breed (P \ 0.05). Two SNPs in Droughtmaster diverged significantly from Angus and Simmental. The SNPs were identified as AHSA2-3 and AHSA2-4, which were closely linked to the three breeds based on pair-wise FST. AHSA2-4 involved a missense mutation. In summary, the GG genotypes in AHSA2-3 and AHSA2-4 may be candidate genotypes associated with heat resistance traits and may serve as valuable genetic markers for breeding of heat-tolerant beef cattle in the future.