This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*

Many therapies are effective in treating varicoceles, including dilation of the pampiniform plexus in males. The most common method of treatment is varicocelectomy. We aimed to assess an alternative technique (microsurgical spermatic [distal end]-superficial or inferior epigastric vein anastomosis) that preserves the normal blood flow pattern for varicocele treatment. We retrospectively analyzed 27 men with varicocele between October 2019 and July 2020. All patients underwent microsurgical spermatic (distal end)-superficial or inferior epigastric vein anastomosis. The prognosis was reviewed retrospectively with an additional survey conducted 3 months after surgery. The mean ± standard deviation of the age was 26.1 ± 7.3 years in patients with microsurgical spermatic (distal end)-superficial or inferior epigastric vein anastomosis. The maximum diameter of the varicocele vein, perineal pain score, sperm density, and forward movement of sperm improved over 3 months after surgery. Microsurgical spermatic (distal end)-superficial or inferior epigastric vein anastomosis is a safe and efficient surgical treatment for varicoceles.
Humans ; Male ; Adolescent ; Young Adult ; Adult ; Varicocele/surgery* ; Retrospective Studies ; Microsurgery/methods* ; Semen ; Anastomosis, Surgical/methods* ; Spermatozoa ; Pain/surgery*

OBJECTIVE: To evaluate the condition of subclinical cardiac damage in children with primary hypertension and the association between serum uric acid and subclinical cardiac damage. METHODS: A retrospective analysis was performed on the medical data of 55 children who were hospitalized and diagnosed with primary hypertension in the Department of Cardiology, Children's Hospital of Soochow University from January 2015 to June 2020. Forty-five healthy children, matched for age and sex, were enrolled as the control group. The two groups were compared in terms of clinical features, laboratory examination, and parameters for left ventricular structure, systolic function, and diastolic function. The correlation of serum uric acid with the parameters for left ventricular structure, systolic function, and diastolic function in children with primary hypertension was analyzed. RESULTS: Compared with the control group, the hypertension group had significantly higher left ventricular mass (LVM), left ventricular mass index (LVMI), and relative wall thickness (RWT) ( CONCLUSIONS Children with primary hypertension may have subclinical cardiac damage such as left ventricular hypertrophy, left ventricular diastolic dysfunction, left atrial enlargement, and proximal aortic dilation. Elevated serum uric acid is significantly associated with cardiac damage in children with primary hypertension.
Blood Pressure ; Child ; Humans ; Hypertension/complications* ; Hypertrophy, Left Ventricular/etiology* ; Retrospective Studies ; Uric Acid

Mesocorticolimbic dopaminergic (DA) neurons have been implicated in regulating nociception in chronic pain, yet the mechanisms are barely understood. Here, we found that chronic constructive injury (CCI) in mice increased the firing activity and decreased the KCNQ channel-mediated M-currents in ventral tegmental area (VTA) DA neurons projecting to the nucleus accumbens (NAc). Chemogenetic inhibition of the VTA-to-NAc DA neurons alleviated CCI-induced thermal nociception. Opposite changes in the firing activity and M-currents were recorded in VTA DA neurons projecting to the medial prefrontal cortex (mPFC) but did not affect nociception. In addition, intra-VTA injection of retigabine, a KCNQ opener, while reversing the changes of the VTA-to-NAc DA neurons, alleviated CCI-induced nociception, and this was abolished by injecting exogenous BDNF into the NAc. Taken together, these findings highlight a vital role of KCNQ channel-mediated modulation of mesolimbic DA activity in regulating thermal nociception in the chronic pain state.

BACKGROUND: In recent years, genetic haploidentical peripheral blood stem cell transplantation has been gradually improved, and haploid allogeneic hematopoietic stem cell transplantation has become an important treatment choice for malignant hematopoietic disease. OBJECTIVE: To observe the clinical efficacy of genetic haploidentical peripheral blood stem cell transplantation for myelodysplastic syndrome. METHODS: The clinical data of 21 myelodysplastic syndrome cases undergoing genetic haploidentical peripheral blood stem cell transplantation were retrospectively analyzed. Modified BU/CY+ATG administration was performed as a pretreatment strategy for haploidentical peripheral blood stem cell transplantation, and the combined use of cyclosporine A+mycophenolate mofetil+short-range methotrexate±basiliximab was adopted to prevent graft-versus-host disease (GVHD). RESULTS AND CONCLUSION: (1) The 21 cases were followed for an median of 333 days (22-1 222 days), with 76% (16/21) infection of granulocyte lack period, 100% (21/21) neutrophil reconstruction, the median implantation time of 12 days (7-17 days), 81% (17/21) platelet engraftment, and the median implantation time of 14 days (7-68 days). (2) The accumulative incidence of GVHD was 52.4% (11/21), including 29% (6/21) of acute GVHD and 24% (5/21) of chronic GVHD. The incidence of hemorrhagic cystitis was 38.1% (8/21). The recurrence rate after transplantation was 4.8% (1/21). (3) The 2-year non-relapse mortality was 48% (10/21), and the 2-year disease-free survival rate was 46.8%. These results show that in the absence of HLA-identical related donors and unrelated donor, genetic haploidentical peripheral blood stem cell transplantation is a safe, effective, feasible and alternative treatment option for myelodysplastic syndrome.

Background: Pathologic response is evaluated according to the extent of tumor regression and is used to esti-mate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorectal cancer patients with liver metastases who underwent hepatectomy. However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the asso-ciation between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients. Patients and methods: In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients. The pathologic response was evaluated according to the tumor regression grade (TRG). The prognostic role of pathologic response in recurrence-free survival (RFS) and overall survival (OS) was assessed using Kaplan–Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal–Wallis/Mann–WhitneyU tests. Results: Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy (median RFS: 9.9 vs. 6.5 months,P= 0.009; median OS: 40.7 vs. 28.1 months,P= 0.040). Multivariate logistic regression and Kruskal–Wallis/Mann–WhitneyU tests showed that metastases with small diameter, metastases from the left-side primary tumors, and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases (allP < 0.05). A decrease in the serum carcinoembryonic antigen (CEA) level after preopera-tive chemotherapy predicted an increased pathologic response rate (P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemother-apy resulted in a higher pathologic response rate when combined with irinotecan-based regimens rather than with oxaliplatin-based regimens. Conclusions: We found that the evaluation of pathologic response may predict the prognosis of Chinese colo-rectal cancer patients with liver metastases after preoperative chemotherapy. Small tumor diameter, long-duration chemotherapy, left primary tumor, and decreased serum CEA level after chemotherapy are associated with increased pathologic response rates.

Our study was to investigate the epidemiological characteristics of M.tuberculosis from a national tuberculosis referral center in China. All strains isolated from TB patients, were genotyped by the RD105 deletion, 8 and 51 SNP loci and VNTR. The high differentiation SNPs of modern Beijing strains were analyzed for protein function and structure. 413 M. tuberculosis were included. Of 379 Beijing lineage M. tuberculosis, 'modern' and 'ancient' strains respectively represented 85.5% (324/379) and 14.5% (55/379). Rv2494 (V48A) and Rv0245 (S103F) were confirmed as high differentiation SNPs associated with modern strains. In a word, Modern Beijing lineage M.tuberculosis was dominant and the structural models suggested that modern sub-lineage may more easily survive in 'extreme' host condition.
China ; epidemiology ; DNA, Bacterial ; genetics ; Genome, Bacterial ; Hospitals, Chronic Disease ; Humans ; Molecular Epidemiology ; Mycobacterium tuberculosis ; classification ; genetics ; isolation & purification ; Phylogeny ; Phylogeography ; Polymorphism, Single Nucleotide ; Tuberculosis ; epidemiology ; microbiology

INTRODUCTIONMultimodality therapy, including preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), has effectively reduced local recurrence rates of rectal cancer over the past decade. However, the benefits and risks of the addition of neoadjuvant CRT to surgery need to be evaluated. This study was to compare the efficacy of TME with versus without preoperative concurrent chemoradiotherapy (CCRT) involving XELOX regimen (oxaliplatin plus capecitabine) in Chinese patients with stages II and III mid/low rectal adenocarcinoma.

METHODSWe randomly assigned patients to the TME group (TME without preoperative CCRT) or CCRT + TME group (TME with preoperative CCRT). The primary endpoint was disease-free survival (DFS); the secondary endpoints were overall survival (OS), local and distant recurrence, tumor response to CRT, toxicity, sphincter preservation, and surgical complications. An interim analysis of the potential inferiority of DFS in the CCRT + TME group was planned when the first 180 patients had been followed up for at least 6 months.

RESULTSA total of 94 patients in the TME group and 90 patients in the CCRT + TME group were able to be evaluated. The 3-year DFS and OS rates were 86.3 % and 91.5 % in the whole cohort, respectively. The 3-year DFS rates of the TME and CCRT + TME groups were 85.7% and 87.9 % (P = 0.766), respectively, and the 3-year OS rates were 90.7 % and 92.3 % (P = 0.855), respectively. The functional sphincter preservation rates of the TME and CCRT + TME groups were 71.3 % and 70.0 % (P = 0.849), respectively. In the TME group, 16 (17.0 %) patients were proven to have pTNM stage I disease after surgery. In the CCRT + TME group, 32 (35.6 %) patients achieved a pathologic complete response (pCR).

CONCLUSIONSPreliminary results indicated no significant differences in the DFS, OS, or functional sphincter preservation rates between the TME and CCRT + TME groups. However, preoperative CCRT with XELOX yielded a high pCR rate. Newer techniques are needed to improve the staging accuracy, and further investigation is warranted.

CLINICAL TRIAL REGISTRATION NUMBERChi CTR-TRC-08000122.

Adenocarcinoma ; Antineoplastic Combined Chemotherapy Protocols ; Chemoradiotherapy ; Combined Modality Therapy ; Deoxycytidine ; analogs & derivatives ; Disease-Free Survival ; Fluorouracil ; analogs & derivatives ; Humans ; Neoadjuvant Therapy ; Neoplasm Staging ; Organoplatinum Compounds ; Prognosis ; Prospective Studies ; Rectal Neoplasms ; Survival Rate

Introduction:Multimodality therapy, including preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), has effectively reduced local recurrence rates of rectal cancer over the past decade. However, the benefits and risks of the addition of neoadjuvant CRT to surgery need to be evaluated. This study was to compare the efficacy of TME with versus without preoperative concurrent chemoradiotherapy (CCRT) involving XELOX regimen (oxaliplatin plus capecitabine) in Chinese patients with stages II and III mid/low rectal adenocarcinoma. Methods:We randomly assigned patients to the TME group (TME without preoperative CCRT) or CCRT+TME group (TME with preoperative CCRT). The primary endpoint was disease-free survival (DFS);the secondary endpoints were overall survival (OS), local and distant recurrence, tumor response to CRT, toxicity, sphincter preservation, and surgical complications. An interim analysis of the potential inferiority of DFS in the CCRT+TME group was planned when the first 180 patients had been followed up for at least 6 months. Results:A total of 94 patients in the TME group and 90 patients in the CCRT+TME group were able to be evaluated. The 3-year DFS and OS rates were 86.3%and 91.5%in the whole cohort, respectively. The 3-year DFS rates of the TME and CCRT+TME groups were 85.7%and 87.9%(P=0.766), respectively, and the 3-year OS rates were 90.7%and 92.3%(P=0.855), respectively. The functional sphincter preservation rates of the TME and CCRT+TME groups were 71.3%and 70.0%(P=0.849), respectively. In the TME group, 16 (17.0%) patients were proven to have pTNM stage I disease after surgery. In the CCRT+TME group, 32 (35.6%) patients achieved a pathologic complete response (pCR). Conclusions:Preliminary results indicated no significant differences in the DFS, OS, or functional sphincter preservation rates between the TME and CCRT+TME groups. However, preoperative CCRT with XELOX yielded a high pCR rate. Newer techniques are needed to improve the staging accuracy, and further investigation is warranted. Clinical trial registration number:Chi CTR-TRC-08000122.