OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

Objective To assess the risk of human Spirometra mansoni infections and investigate the knowledge, attitude and practice (KAP) towards sparganosis mansoni among residents in Henan Province, so as to provide insights into formulation of the sparganosis mansoni control measures. Methods Qinling Village in Fugou County of Zhoukou City, Bali Village in Yancheng District of Luohe City, Duzhai Village in Puyang County of Puyang City and Doushan Village in Luoshan County of Xinyang City were sampled as survey sites in Henan Province from July to August 2023, and more than 40 frogs were sampled from ponds or streams in each survey site for detection of Sparganum mansoni infections. At least 150 residents were sampled using a cluster sampling method from each survey site, and the sero-prevalence of anti-S. mansoni IgG antibody was estimated. In addition, a questionnaire survey was conducted on the KAP towards sparganosis mansoni among participants, and the proportion of eligible KAP, rate of correct KAP and KAP scores were calculated. Results A total 229 frogs were collected from 4 survey sites in 2023, and the overall prevalence of S. mansoni infection was 4.37% (10/229) in frogs, with 7.75% (10/129) prevalence in wild frogs and 0 in farm-bred frogs. A questionnaire survey was performed among 649 residents sampled from 4 survey sites, and 649 serum samples were collected. The seroprevalence of anti-S.mansoni IgG antibody was 0.15% (1/649) and the overall proportion of eligible KAP was 23.73% (154/649) among participants. There were age- (χ² = 30.905, P = 0.000), educational level- (χ² = 41.011, P = 0.000), and occupation-specific proportions of eligible KAP among participants (χ² = 10.721, P = 0.005), and the proportion of eligible KAP decreased with age (χ² _trend = 22.717, P = 0.000) and increased with education levels (χ² _trend = 40.025, P = 0.000). The rates of correct KAP towards sparganosis mansoni were 40.81% (2 119/5 192), 96.66% (1 882/1 947) and 63.81% (3 727/5 841) (χ² = 1 913.731, P = 0.000) among residents, respectively. The rates of correct KAP towards sparganosis mansoni varied significantly among survey sites (χ² = 136.872, 42.347 and 255.157; all P values= 0.000, with the highest rate of correct knowledge (51.94%, 748/1 440) and practices (75.86%, 1 229/1 620) in Yancheng District of Luohe City and the highest rate of correct attitudes in Puyang County of Puyang City (99.11%, 446/450) (all P values< 0.05). Conclusions There is still a high transmission risk of sparganosis mansoni in Henan Province, and the KAP towards sparganosis mansoni is required to be improved among residents.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Objective:To investigate the clinical effect of anterolateral thigh flow-through chimeric perforator free flap transplantation in the treatment of upper limb complex tissue defects with main artery injury.Methods:The study was a retrospective observational study. From May 2019 to January 2022, 11 patients with upper limb complex tissue defects combined with main artery injury who met the inclusion criteria were admitted to the Department of Hand, Foot and Ankle Surgery of General Hospital of Ningxia Medical University, including 7 males and 4 females, aged from 18 to 56 years. After debridement, the area of skin and soft tissue defects was from 20 cm×6 cm to 32 cm×10 cm, and the exposed area of dead cavity or deep tissue was from 7 cm×4 cm to 10 cm×7 cm. Three patients had radial artery defects with a length of 4 to 7 cm; two patients had ulnar artery defects with a length of 5 to 8 cm; 4 patients had defects in both ulnar and radial arteries with a length of 3 to 7 cm; and in two patients, the ulnar, radial and brachial arteries were all defective with a length of 4 to 8 cm. The anterolateral thigh flow-through chimeric perforator flap was designed and cut. The skin flap area was from 22 cm×7 cm to 32 cm×11 cm, the chimeric muscle flap area was from 7 cm×4 cm to 10 cm×7 cm, and the length of the flow-through vessel in the "T" shaped vessel pedicle was from 4 to 8 cm. When transplanting the skin flap, the proximal end of the vascular pedicle was anastomosed with the proximal end of the recipient site, and the distal end of the vascular pedicle was anastomosed with the more normal blood vessel at the distal end of the forearm; the invalid cavity was filled with the muscle flap. The donor site wounds of tissue flap were closed directly or treated with skin grafting. After operation, the blood supply and survival of the flap, the survival of the distal limb, and the survival of the skin graft at the flap donor site were observed. Computed tomography angiography (CTA) was performed to observe the patency of the proximal and distal anastomotic arteries from 2 to 4 weeks after surgery. During follow-up, the texture of the flap, the survival of the grafted skin and the healing of the donor area were observed.Results:One patient (complete forearm disconnection) developed distal limb blood disorder on 5 days after surgery. CTA examination suggested embolization of the distal anastomosis of the flow-through artery. more muscle and skin and soft tissue necrosis of the distal limb showed in emergency exploration. So, amputation was performed ultimately. No vascular crisis occurred in the skin flaps of the remaining 10 patients, and all skin flaps, distal limbs and the skin grafts in flap donor sites survived well. Two to 4 weeks after surgery, the proximal and distal ends of the anastomosed arteries were good in the patency. Follow-up for 11-37 months, the flap texture was good, and all donor site wounds healed well.Conclusions:The use of anterolateral thigh flow-through chimeric perforator flap to repair upper limb complex tissue defects accompanied by main artery injury can improve the success rate of limb salvage, which can be promoted in clinical practice.

Objective:To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED).Methods:Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed.Results:Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 μg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases.Conclusions:CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.

Objective To investigate the molecular mechanism of Brusatol(BRU)regulating apoptosis of Hela cells through TLR9-MyD88 signaling pathway.Methods Hela cells preserved in our laboratory were treated with Brucea javanica at different concentrations(0,5.0,10.0,20.0,40.0,80.0 nmol·L-1).Hela cells were divided into Control group(normal cultured Hela cells),BRU-L group(treated with 10.0 nmol·L-1 Brucea javanica)and BRU group-H(treated with 20.0 nmol·L-1 Brucea javanica)Cells were treated with nmol·L-1 of Brucea javanica),BRU+pcDNA-NC group(transfected with pcDNA-NC+20.0 nmol·L-1 of Brucea javanica),BRU-H+pcDNA-TLR9 group(transfected with pcDNA-TLR9+20.0 nmol·L-1 of Brucea javanica).Cell proliferation was detected by CCK-8 and EdU methods.Apoptosis was detected by TUNNEL staining and flow cytometry.The protein expression levels of TLR9,MyD88,Bax,Bcl-2,Cleaved Caspase-3 and Cleaved Caspase-9 were detected by Western blot.Cell apoptosis and mitochondrial membrane potential detection kit(JC-1)were detected by flow cytometry,and the contents of adenosine triphosphate(ATP)and reactive oxygen species(ROS)were detected by ELISA.Results Compared with 0 nmol·L-1 group,the survival rate and IC50 value of 10 nmol·L-1 group were significantly decreased(P<0.05).After stimulation of BRU with different concentrations,the proliferation ability of cells was significantly decreased in a dose-dependent manner(P<0.05).Compared with control group,the 5-ethynyl-2'-deoxyuracil(EDU)positive cell rate,TUNEL positive cell rate,apoptosis rate and Bcl-2 protein of cells in BRU-L,BRU-H and pcDNA-NC groups were significantly decreased.The protein levels of TLR9 and MyD88,Bax,Bax/Bcl-2,Cleaved Caspase-3 and Cleaved Caspase-9 were significantly increased(P<0.05).In control group,BRU-L,BRU-H group/BRU-H+pcDNA-NC,there was a continuous decreasing trend(P<0.05).Compared with the BRU-H+pcDNA-NC group,the EDU positive cell rate,TUNEL positive cell rate,apoptosis rate and Bcl-2 protein in the BRU-H+pcDNA-TLR9 group were significantly increased.The protein levels of TLR9 and MyD88,Bax,Bax/Bcl-2,Cleaved Caspase-3 and Cleaved Caspase-9 were significantly decreased(P<0.05).Compared with Control group,JC-1 level and ATP content in BRU-L,BRU-H and BRU-H+pcDNA-NC groups were significantly decreased,while ROC content and mitotracker positive cell level were significantly increased(P<0.05).Compared with BRU-L group,JC-1 level and ATP content in BRU-H group and BRU-H+pcDNA-NC group were further decreased,while ROC content and mitotracker positive cell level were further increased(P<0.05).Compared with the BRU-H+pcDNA-NC group,the levels of JC-1 and ATP in the BRU-H+pcDNA-TLR9 group were increased,while the levels of ROC,mitotracker staining positive cells were decreased(P<0.05).Conclusion Brucea javanica can produce Hela cell proliferation by regulating TLR9-MyD88 signaling pathway.

Objective:To investigate the value of aspartate aminotransferase/lymphocyte ratio (ALR), γ-glutamyltranspeptidase/lymphocyte ratio (GLR) and aspartate aminotransferase/alanine aminotransferase ratio (AAR) in predicting the recurrence of hepatocellular carcinoma after liver transplantation.Methods:The retrospective cohort study was conducted. The clinicopathological data of 178 patients with hepatocellular carcinoma who underwent liver transplantation in Tianjin First Central Hospital from July 2014 to June 2018 were collected. There were 156 males and 22 females, aged (54±9)years. All patients received the first time of orthotopic liver transplantation. Observation indicators: (1) follow-up; (2) the predictive value and cutoff value of each index for tumor recur-rence of patients with hepatocellular carcinoma after liver transplantation; (3) analysis of risk factors for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation; (4) cons-truction and evaluation of the predictive model for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and the Log-rank test was used for survival analysis. Factors with P<0.05 in univariate analysis were included in multivariate analysis. Univariate analysis and multivariate analysis were performed by COX proportional risk regression model with forward method. The regression coefficient was used to build the prediction model. The receiver operating characteristic curve was drawn, and the area under curve (AUC) was used to evaluate the predictive ability of prediction model. Results:(1) Follow-up. All 178 patients with hepatocellular carcinoma were followed up for 36(range, 1?74)months after liver transplantation. During the follow-up, there were 41 patients died, 61 patients with tumor recurrence and 117 cases without tumor recurrence. The 3-, 5-year overall survival rates and 3-, 5-year tumor recurrence free survival rates of patients after liver transplantation were 72.8%, 69.9% and 57.3%, 52.8%, respectively. (2) The predictive value and cutoff value of each index for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation. The AUC of preoperative serum alpha fetoprotein (AFP), tumor diameter, ALR, GLR, neutrophil to lymphocyte ratio, AAR in recipients were 0.76, 0.70, 0.69, 0.65, 0.64, 0.65 (95% confidence interval as 0.68?0.83, 0.61?0.79, 0.61?0.77, 0.57?0.74, 0.56?0.73, 0.56?0.74, P<0.05), and the corresponding best cutoff value of each index were 228.00 μg/L, 5.25 cm, 92.90, 122.40, 3.00, 2.42. (3) Analysis of risk factors for tumor recurrence of patients with hepato-cellular carcinoma after liver transplantation. Results of multivariate analysis showed the preoperative serum AFP >228.88 μg/L, number of tumor as multiple, tumor diameter >5.25 cm, ALR >92.90, AAR >2.42 were indepen-dent risk factors for tumor recurrence of hepatocellular carcinoma after liver transplantation ( hazard ratio=3.13, 1.90, 2.66, 2.40, 2.75, 95% confidence interval as 1.81?5.41, 1.08?3.35, 1.49?4.74, 1.40?4.11, 1.54?4.91, P<0.05). (4) Construction and evaluation of the predictive model for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation. According to the results of multivariate analysis, the preoperative serum AFP, number of tumor, tumor diameter, ALR, AAR were used to construct the predictive model for tumor recurrence of hepatocellular carcinoma after liver transplantation. The AUC, best cutoff value, specificity and sensitivity of the predictive model were 0.83 (95% confidence interval as 0.76?0.89, P<0.05), 5.5, 80.3% and 73.8%. Of the 178 patients, there were 110 patients with low risk of tumor recurrence (scoring as 0?5) and 68 patients with high risk of tumor recurrence (scoring as 6?16) after liver transplantation. The 1-, 3-, 5-year tumor recurrence free survival rates and 1-, 3-, 5-year overall survival rates of patients with high risk of tumor recurrence were 27.7%, 18.2%, 18.2% and 63.7%, 48.9%, 48.9%, respectively. The above indicators of patients with low risk of tumor recurrence were 92.3%, 82.4%, 74.6% and 90.4%, 87.7%, 83.6%, respectively. There were significant differences of the above indicators between patients with high risk of tumor recurrence and low risk of tumor recurrence ( χ2=67.83, 21.95, P<0.05). Conclusions:The preoperative serum AFP, number of tumor, tumor diameter, ALR, AAR are independent influencing factors for tumor recurrence of hepato-cellular carcinoma after liver transplantation. The predictive model constructed based on the above indexes has a good prediction efficiency.

Detection and identification standard of hookworm—Hookworm larvae coproculture techniques (WS/T 791—2021) is the first recommended technical standard for hookworm detection and species identification using the hookworm larvae coproculture technique in China. This standard was issued on November 23, 2021, and had been in effect since May 1, 2022. This article provides a detailed interpretation pertaining to the background, drafting process, main contents, and dos and don’ts for better understanding and application of this standard among professionals working in disease control and prevention institutions and medical institutions.

Mendelian Randomization Analysis ; Bone Density ; Genome-Wide Association Study ; Minerals ; Life Expectancy ; Polymorphism, Single Nucleotide