Objective To evaluate the predictive value of triglyceride-glucose body mass index(TyG-BMI),atherogenic index of plasma(AIP),and postprandial glucose excursion(PPGE)for sarcopenia in patients with type 2 diabetes mellitus(T2DM).Methods An observational cohort trial was conducted on 590 hospitalized T2DM patients(322 males and 268 females)admitted to Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University between January 2023 and December 2024.General demographic data and key metabolic indicators,including fasting plasma glucose(FPG),postprandial 2-hour plasma glucose(PPG),triglyceride(TG)were collected,and then TyG-BMI,AIP,and PPGE were calculated.Based on the Asian Working Group for Sarcopenia(AWGS)2019 criteria,they were divided into a sarcopenia group(n=140)and a non-sarcopenia group(n=450).After 1∶1 propensity score matching(PSM),102 patients with sarcopenia were matched with 102 without.Differences in metabolic indicators FPG,PPG,TyG-BMI,AIP and PPGE were compared between the 2 groups.Spearman correlation analysis was conducted to assess correlations of these indicators with sarcopenia.Conditional logistic regression analysis was performed to identify independent risk factors,and receiver operating characteristic(ROC)curves were plotted to assess predictive performance.An external validation cohort consisting of 192 T2DM patients from Department of Endocrinology of Jiangbei Branch of First Affiliated Hospital of Army Medical University between January 2023 and December 2024 was included to validate the prediction model.Results After PSM,the baseline data of the 2 groups was balanced(P>0.05).The sarcopenia group showed higher levels of PPG,AIP,and PPGE,but lower TyG-BMI value than the non-sarcopenia group(all P=0.001).Spearman correlation analysis revealed that the TyG-BMI was negatively correlated(r=-0.404,P=0.001),whereas AIP and PPGE were positively correlated with concomitant sarcopenia(r=0.280,P=0.001;r=0.372,P=0.001)in the T2DM patients.Conditional logistic regression analysis identified AIP(OR=14.367)and PPGE(OR=1.245)as independent risk factors,while TyG-BMI(OR=0.966)as independent protective factors.ROC curve analysis revealed that the area under the curve(AUC)of the combined model of TyG-BMI,AIP and PPGE in predicting sarcopenia was 0.918,and the AUC value was 0.954 in external validation,with good sensitivity and specificity.Conclusion TyG-BMI,AIP,and PPGE are important metabolic predictors in T2DM patients with sarcopenia.Their combination has good screening value for sarcopenia,and can be applied in external prediction for T2DM patients.

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.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis

Objective:To investigate the clinical features, diagnostic methods and treatments of left ventricular apical fibroma.Methods:The clinical manifestations, ECG, imaging features and treatment plans of 2 patients with giant fibroma of left ventricular apex diagnosed in September 2020 and May 2022 were analyzed retrospectively, and the related literature was reviewed.Results:Both patients had slight chest distress and discomfort after activities. The ECG showed T-wave inversion of different degrees, which were misdiagnosed as “myocarditis” and “coronary heart disease” respectively. The cardiac magnetic resonance imaging and echocardiography showed left ventricular apical mass. Coronary artery stenosis was not found in coronary angiography. One patient required conservative treatment, and there was no significant change in clinical symptoms and tumor size in the follow-up for half a year; Another patient underwent cardiac mass removal, and the pathological examination after operation confirmed that it was cardiac fibroma, and there was no recurrence in the follow-up 2 years.Conclusion:Fibroma of left ventricular apex is a rare cardiac tumor, which is easy to be missed and misdiagnosed, and is one of the rare causes of T-wave inversion. Cardiac magnetic resonance imaging, CT and echocardiography are commonly used imaging methods to diagnose cardiac fibroma, and surgical resection is an effective treatment.

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.

This paper mainly studied the effect of Xiyanping injection on the bacterial endotoxin lipopolysaccharide (LPS)-induced fever in rabbits, preliminarily investigated the mechanisms, and provided pharmacological basis for the clinical application. The rabbit model of endotoxin-induced fever was established by using LPS as the inducer; The changes of rectal temperature were measured; The levels of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and phospholipaseA2 (PLA2) in the serum were measured; The levels of PGE2, cyclic adenosine monophosphate (cAMP), and arginine vasopressin (AVP) in cerebrospinal fluid as well as hypothalamus were detected. The animal welfare and experimental process are in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University in this study. The results showed that Xiyanping injection (12.5, 25, and 50 mg·kg^-1) could significantly reduce LPS-upregulated body temperature of rabbits, and the duration of action could reach 5.5-8.5 h. At the doses of 25 and 50 mg·kg^-1, the antipyretic effect of Xiyanping injection was comparable to that of analgin injection (50 mg·kg^-1). Furthermore, Xiyanping injection and analgin injection both reduced the levels of PGE2, IL-1β, TNF-α, and PLA2 in the serum of febrile rabbits to the varying degrees. In addition, Xiyanping injection also down-regulated the levels of PGE2, cAMP, and AVP in the hypothalamus, and PGE2 and cAMP in the cerebrospinal fluid. The level of AVP in the cerebrospinal fluid was up-regulated. This study indicated that Xiyanping injection could significantly improve the endotoxin-induced fever in rabbits, and mechanisms were closely related to the regulation of the levels of PGE2, TNF-α, IL-1β, PLA2, cAMP, and AVP in serum, hypothalamus, and cerebrospinal fluid.

: Objective: To investigate the effects of ezrin enhancer knockout on ezrin gene expression, cell proliferation and migration of human esophageal carcinoma Eca-109 cells. : Methods: The CRISPR/Cas9 recombinant plasmids targeting upstream/downstream of human ezrin enhancer were co-transfected into human esophageal carcinoma Eca-109 cells, and the cell line Eca-C2 with ezrin enhancer knockout was screened by purinomycin. Then the expression levels of ezrin mRNAand protein in Eca-C2 cells were detected by Real-time quantitative PCR (qPCR) and Western blotting, respectively; The expression levels of MAPK-pathway-related proteins were detected by protein array technology; and the effects of ezrin enhancer knockout on the proliferation and migration of Eca-C2 cells were analyzed by WST-1 method and wound-healing assay, respectively. : Results:The human esophageal carcinoma cell line Eca-C2 with stable ezrin enhancer knockout was established successfully. Compared with control cells, the mRNA and protein expressions of ezrin in Eca-C2 cells were significantly reduced (all P<0.05).Among the 17 detected MAPK pathway related proteins in Eca-C2 cells, 9 proteins (AKT, CREB, GSK3b, MKK6, mTOR, P38, P53, P70S6K and RSK1) were down-regulated, and the cell proliferation and migration were significantly inhibited (all P<0.05). Conclusion: ezrin enhancer knockout can significantly inhibit the cell proliferation and migration of human esophageal carcinoma Eca-109 cells.

Bile acids( BAs),the major constituents of bile,are also known to be potential biomarkers of various diseases,especially liver disease. The systematic analysis of BAs is believed to be of great importance towards the clarification of the effective material basis for bile-type medicines,and the diagnosis and therapy of related diseases as well. As a part of systematic study on bile-type medicine ongoing in our group,this study lays emphasis on the isomer discrimination,and the improvement of analytical method of BAs. Further,this method was subsequently applied to elucidate in depth the chemical profile of BAs in yak bile. Regarding isomer discrimination for BAs,we constructed relative response-collision energy curves( RRCECs) by high performance liquid chromatographyion trap-time of flight-mass spectrometry( HPLC-IT-TOF-MS) in combination with high performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometry( HPLC-Qtrap-MS). As a result,both the optimum collision energy( OCE) and CE_(50) exhibited great correlations with structural characteristics,thus enabling the isomer distinguishing,such as unconjugated BAs,glycine-conjugated BAs,and taurine-conjugated BAs. According to information provided by mass spectrometry,the comparison of OCE and CE_(50),retention time matching,combined with reference substances and database retrieval,a total of 30 bile acid derivatives were observed and identified in yak bile. The newly developed method could serve as a feasible tool for the in-depth characterization of BAs in bile and biological samples.
Animals ; Bile ; chemistry ; Bile Acids and Salts ; chemistry ; Cattle ; Chromatography, High Pressure Liquid ; Mass Spectrometry ; Taurine

Objective To investigate the expressions of a disintegrin and metalloprotease 17 (ADAM17) and epidermal growth factor recepter (EGFR) in human esophageal squamous cell carcinoma (ESC),and to explore their relationship with clinicopathological characteristics.Methods The paraffin specimens in postoperative pathological tissues of 66 ESC patients in the Third People's Hospital of Hefei from January 2013 to December 2017 were selected.Expressions of ADAM17 and EGFR proteins were examined by using immunohistochemistry in 66 cases of ESC tissues and 33 cases of adjacent tissues of the tumors.The relationship of ADAM17 and EGFR with clinicopathological features was analyzed.Kendall method was used to detect the expression correlation of ADAM17 and EGFR.Results The positive rate of ADAM17 protein in ESC tissues was higher than that in the adjacent tissues of the tumors [68.2 ％ (45/66) vs.33.3 ％ (11/33),x2 =10.874,P =0.001].The positive rate of EGFR protein in ESC tissues was higher than that in the adjacent tissues of the tumors [66.7 ％ (44/66) vs.39.4 ％ (13/33),x2 =6.699,P =0.01].The expressions of ADAM17 and EGFR protein were related with ESC pathological TNM staging,infiltration depth,lymph node metastasis (x2 =4.797,4.890,6.089;8.790,8.766,10.154,respectively,all P ＜ 0.05).ADAM17 expression was positively correlated with EGFR protein (r,=0.368,P ＜ 0.05).Conclusions ADAM17 and EGFR are highly expressed in human ESC.Besides,ADAM17 and EGFR have the interaction in the occurrence and development of esophageal cancer.Joint detection may help to determine the degree of metastasis and evaluate prognosis.

Objective To study the curative efficacy of Ningmitai capsule unite amsulosin hydrochloride sustained realeased capsules treatment ofⅢ type B prostatitis and its effects on level of the prostate fluid of interleukin-10(IL-10), tumor necrosis factor alpha, prostaglandin E2.Methods 104 patients withⅢtype B prostatitis who received therapy from December 2015 to October 2016 in our hospital were selected as research objects, according to the treatment were divided into observation group and control group , the observation group was treated with Ningmitai capsules unite Tamsulosin hydrochloride sustained realeased capsules while the control group was treated with Tamsulosin hydrochloride sustained realeased capsules.Comparison curative effect ,before and after the treatment of chronic inflammatory prostate integral index, maximum urinary flow rate, average urine flow rate;Analysis before and after treatment prostate fluid of interleukin-10, tumor necrosis factor alpha, prostaglandin E2 level and WBC count.Results After treatment, the observation group total effective rate was 90.4%, significantly higher than the control group (P<0.05);After treatment, the observation group in the prostatic fluid IL-10, the TNF-α, PGE-2, the WBC levels were significantly lower than the control group (P<0.05),and after the treatment,chronic inflammatory prostate integral index of observation group was obviously lower than the control group, the maximum urinary flow rate, average urine flow rate is significantly higher than the control group (P<0.05).Conclusion Ningmitai capsules unite amsulosin hydrochloride sustained realeased capsules treatment Ⅲ type B prostatitis has significantly clinical curative effect, can pass down the prostate fluid of IL-10, the TNF alpha, PGE-2 levels, relieve the clinical symptoms.

Objective:To monitor the dynamic changes in coagulation function and assess their clinical significance in patients with gas-tric cancer by using thromboelas to gram (TEG). Methods:A total of 178 patients with gastric cancer from March 2014 to May 2015 in Xinxiang Central Hospital were selected as the experimental group. The patients were grouped based on different tumor stages, inva-sion depths, and lymph node metastasis. The TEG results of all patients were dynamically monitored before and after operation, and 60 healthy persons were selected as normal control group. Blood coagulation change was analyzed by comparing the TEG test results. Results:Compared with those of the control group, the TEG parameters of the experimental group showed significantly decreased R and K values, as well as significantly increased Angle, CI, and MA values, and the differences were statistically significant (P<0.05). In the experimental group, the K values were significantly decreased after operation, whereas Angle, MA, and CI were significantly in-creased (P<0.05). No significant changes were observed in R, LY30, and others. TEG values were significantly different in the compari-son of values for tumor patients with different stages, different tumor infiltration degrees, and with or without lymphatic metastasis. Conclusion:Blood hypercoagulability in the perioperative period was observed in patients with gastric cancer and was positively corre-lated with tumor stages, tumor infiltration degrees, and lymphatic metastasis. Dynamic monitoring of gastric cancer perioperative TEG can provide valuable information for clinical treatment, improve the safety of gastric cancer surgery, and reduce postoperative compli-cations associated with active clinical significance.