Immunoglobulin A nephropathy （IgAN） is the primary glomerulonephritis with the highest incidence rate in the world. It is also the main cause of end-stage renal disease （ESRD） in China， which has brought heavy economic burden to the society and patient families. Traditional Chinese medicine （TCM） has certain advantages in treating IgAN. In TCM， IgAN is classified into consumptive disease， hematuria， and edema categories， with the location in the kidney and involving the lung， liver， and spleen. Professor Ren Jixue， a master of TCM， believes that kidney deficiency and spleen deficiency are the root causes of IgAN， and the throat is the source of the disease. He proposed the theory of throat-kidney correlation and used the method of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat to treat IgAN， achieving significant therapeutic effects. Studies have shown that IgAN is closely related to mucosal immune defense. IgAN patients often experience recurrent and gradually worsening symptoms due to mucosal infections， and polymeric Ig receptor （PIgR） is an important component of mucosal defense function. The lack of PIgR leads to the accumulation of IgA molecules in the mucosal lamina propria， and the molecules enter the bloodstream in large quantities and ultimately deposit in the kidneys， causing kidney damage. Complement regulatory protein complement receptor type 1 （CR1） exists on red blood cells and glomeruli and has the function of inhibiting the activation and differentiation of B cells， clearing immune complexes， and inhibiting excessive activation of the complement system. Therefore， regulating the immune defense function through the mucosal-renal axis mediated by PIgR-CR1 will be an important target for preventing and treating IgAN. Based on the theory of throat-kidney correlation， this article explores the effects and molecular mechanisms of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat in preventing and treating IgAN by regulating the mucosal-kidney axis mediated by PIgR-CR1. It provides effective theoretical support and a scientific basis for TCM prevention and treatment of IgAN based on the theory of throat-kidney correlation.

Immunoglobulin A nephropathy （IgAN） is the primary glomerulonephritis with the highest incidence rate in the world. It is also the main cause of end-stage renal disease （ESRD） in China， which has brought heavy economic burden to the society and patient families. Traditional Chinese medicine （TCM） has certain advantages in treating IgAN. In TCM， IgAN is classified into consumptive disease， hematuria， and edema categories， with the location in the kidney and involving the lung， liver， and spleen. Professor Ren Jixue， a master of TCM， believes that kidney deficiency and spleen deficiency are the root causes of IgAN， and the throat is the source of the disease. He proposed the theory of throat-kidney correlation and used the method of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat to treat IgAN， achieving significant therapeutic effects. Studies have shown that IgAN is closely related to mucosal immune defense. IgAN patients often experience recurrent and gradually worsening symptoms due to mucosal infections， and polymeric Ig receptor （PIgR） is an important component of mucosal defense function. The lack of PIgR leads to the accumulation of IgA molecules in the mucosal lamina propria， and the molecules enter the bloodstream in large quantities and ultimately deposit in the kidneys， causing kidney damage. Complement regulatory protein complement receptor type 1 （CR1） exists on red blood cells and glomeruli and has the function of inhibiting the activation and differentiation of B cells， clearing immune complexes， and inhibiting excessive activation of the complement system. Therefore， regulating the immune defense function through the mucosal-renal axis mediated by PIgR-CR1 will be an important target for preventing and treating IgAN. Based on the theory of throat-kidney correlation， this article explores the effects and molecular mechanisms of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat in preventing and treating IgAN by regulating the mucosal-kidney axis mediated by PIgR-CR1. It provides effective theoretical support and a scientific basis for TCM prevention and treatment of IgAN based on the theory of throat-kidney correlation.

Objective To investigate the effect and mechanism of miglitol on regulating the energy metabolism of brown adipocytes by activating UCP1 and preventing cold injury in mice after cold exposure. Methods Primary brown adipocytes were induced into mature adipocytes, the effect of miglitol on the viability of brown adipocytes was investigated by MTT method, the lipid droplet consumption level of cells after drug administration was investigated by Oil Red O staining technology, and the level of UCP1, a key protein of thermogenesis in brown adipocytes, was detected by Western blotting. The activity of anti-frostbite was investigated in cold exposure at 4 ℃ and −20 ℃. KM mice, which were randomly divided into control group, cold exposure group, miglitol group and all-trans retinoic acid group, and after 7 days of repeated administration, the body surface temperature of mice was detected by infrared thermal imaging system, the anal temperature change was detected by anal thermometer, and the expression levels of UCP1 and PGC1-α in adipose tissue were detected by immunoblotting. Results Compared with the control group, the lipid droplet consumption and UCP1 expression levels in brown adipocytes in the miglitol group were significantly increased. The levels of body surface temperature and rectal temperature increased significantly after cold exposure, and the levels of UCP1 and PGC1α in the brown adipose tissue of mice increased significantly, which indicated that the miglitol could activate the critical proteins UCP1 and PGC1α of the thermogenesis pathway, increase the thermogenesis of mice after cold exposure, and thus improve the effect of cold injury for toe swelling. Conclusion Miglitol could play a role in improving cold injury and body temperature in mice by increasing the level of UCP1 and PGC1α, which are key targets of the thermogenesis pathway to promote the thermogenesis of brown fat.

Objective: To investigate the expression and functional role of FK506 binding protein 10 (FKBP10) in oral squamous cell carcinoma (OSCC), and to provide a research basis for the estimated prognosis and targeted therapy of OSCC. Methods: A total of 284 OSCC samples and 19 normal samples were selected from the Cancer Genome Atlas (TCGA) database, and diagnostic analysis was performed to determine mRNA expression. Survival analysis for FKBP10 and OSCC was conducted on a gene expression profile interaction analysis website. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression of FKBP10 in four OSCC cell lines and SAS and SCC9 cells transfected with siRNA. The cell proliferation ability of FKBP10-silenced cells was detected using the CCK8 method, and the cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration and invasion ability were detected through wound healing and invasion experiments. The expression changes of total protein and phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT) after FKBP10 silencing were analyzed by proteomics and Western Blot. Results: According to the analysis of gene expression levels, the mRNA expression level of FKBP10 in OSCC was significantly higher than that in normal tissues (P < 0.001). In terms of diagnosis, the expression level of FKBP10 has unique diagnostic value for OSCC (P < 0.05). The survival analysis of FKBP10 and OSCC showed that a high expression of FKBP10 led to a decrease in patient survival and poor prognosis (P < 0.05). The expression of FKBP10 mRNA and protein in OSCC cell lines was higher than that in normal oral keratinocytes (P < 0.001). Silencing FKBP10 can reduce the proliferation, invasion, and migration ability of SAS and SCC9 (P < 0.001), and also block their cell cycle in the G0/G1 phase (P < 0.001), with a significant increase in apoptosis (P < 0.05). Protein mass spectrometry and Western blot analysis revealed that FKBP10 silencing significantly downregulated the expression of multiple proteins in the RAP1 signaling pathway, mainly RAP guanine nucleotide exchange factor 1 (RAPGEF1) (P < 0.05) and the phosphorylation of PI3K-AKT proteins (P < 0.05). Conclusion FKBP10 is highly expressed in OSCC, leading to poor prognosis for patients. Downregulated FKBP10 expression can inhibit the proliferation, migration, and invasion ability of OSCC cells, hinder cell cycle progression, and promote apoptosis via the RAP1-PI3K-AKT axis. FKBP10 is a potential therapeutic target and prognostic biomarker for OSCC.

Objective To investigate the 90%effective dose(ED90)of ciprofol combined with alfentanil in inhibiting gastroscopy insertion response in elderly patients.Methods 110 patients were selected to undergo painless gastroscopy examination on a scheduled basis.110 patients were randomly divided into ciprofol group alone(group H,n=57)and ciprofol group combined with alfentanil 5 μg/kg(group A,n=53).The trial was conducted according to the Biased coin design up-and-down(BCD-UDM)sequential.Patients in group H were given only intravenous infusion of ciprofol and patients in group A were pre-infused with intravenous alfentanil at 5μg/kg,followed by intravenous infusion of ciprofol,and gastroscopy was initiated when the modified observer's assessment of alertness/sedation scale(MOAA/S)was≤1 point.The initial dose of ciprofol was 0.200 mg/kg in all cases,and the adjacent isotropic dose was 0.030 mg/kg.If the patient's MOAA/S was still>1 or the patient had a response that interfered with the operative examination,such as choking or body movement,during gastroscopy placement,2.0 min after the intravenous infusion of ciprofol,was regarded as an ineffective response,then the next patient was elevated by one dose gradient.If the anesthetic effect of the previous patient was judged to be a valid response,the next patient was randomized to a dose according to the BCD-UDM,with an 11%(b=0.11)probability of decreasing the dose gradient by one dose,and an 89%(1-b=0.89)probability of remaining unchanged,and the experiment was terminated at the 45th effective response in each group.Probabilistic unit regression analysis was used to calculate the ED90,95%effective dose(ED95),and 95%confidence intervals(CI)for the inhibition of gastroscopy placement response with ciprofol alone and the combination of 5 μg/kg alfentanil in elderly patients.Results The ED90 of ciprofol in group A was 0.296 mg/kg(95%CI:0.275～0.338),and ED95 was 0.310 mg/kg(95%CI:0.291～0.383);The ED90 of ciprofol in group H was 0.407 mg/kg(95%CI:0.390～0.447),and ED95 was 0.420 mg/kg(95%CI:0.402～0.483).Compared with group H,the total amount of ciprofol was significantly reduced in group A,the time of awakening and time of leaving the hospital were significantly shorter,and the incidence of intraoperative hypotension and hypoxemia was significantly lower,the differences were statistically significant(P<0.05).Conclusion The ED90 of ciprofol combined with 5 μg/kg of alfentanil and ciprofol alone in inhibiting gastroscopy implantation in elderly patients are 0.296 mg/kg and 0.407 mg/kg respectively.

The pancreatojejunostomy is one of the most challenging steps in pancreatic reconstruction surgery,and its success directly impacts the patient's prognosis.The pancreas has characteristics such as being narrow at the top and wide at the bottom,fragile in texture,rich in digestive enzymes,and subject to constant intestinal peristalsis.These factors can easily lead to the loosening of the pancreatojejunostomy site and the occurrence of postoperative pancreatic fistula.Through mechanical modeling analysis and a summary of clinical practice,the authors propose a pancreatojejunostomy method based on mechanical principles.This method is summarized as"1-tube,2-needle,3-suture"method,which refers to one pancreatic duct stent tube,two types and two strands of different sutures,and three different suturing techniques.This article will provide a detailed introduction to this operative method and deeply analyze its technical principles.Additionally,a retrospective analysis of cases from the authors'center found that this method can effectively reduce the incidence of postoperative pancreatic fistula.

Objective To explore the influencing factors of type 2 diabetes mellitus(T2DM)complicated with metabolic syndrome(MS)and investigate the correlation between the level of 25(OH)D3 and T2DM combined with MS.Methods 592 in patients with T2DM admitted to the Department of Endocrinology of Shenzhen Second People's Hospital were selected from January to December 2020.They were divided into simple T2DM group(T2DM,n=194)and T2DM combined with MS group(MS,n=398).Results Compared with the T2DM group,the MS group had lower 25(OH)D3 levels[26.30(20.50,32.39)vs 24.20(20.16,29.47),P<0.05].Spearman correlation analysis showed that 25(OH)D3 was negatively correlated with MS,FPG,TG,LDL-C,and 24 hUAlb(P<0.05 or P<0.01).Logistic regression analysis showed that 25(OH)D3 was a protective factor for T2DM combined with MS.Conclusions Patients with T2DM and MS have lower 25(OH)D3 levels.25(OH)D3 is a protective factor for T2DM combined with MS.

Sheep pox is widespread worldwide and is the most severe animal pox virus infection. This study aimed to identify the key microRNAs (miRNAs) differentially expressed in the exosomes of sheep poxvirus-infected cells and their target genes and related pathways and provide a theoretical basis for an in-depth understanding of the molecular mechanisms of sheep poxvirus-infected cells. In this study, the differentially expressed miRNAs were verified by quantitative polymerase chain reaction (qPCR), and the target genes of miRNAs were predicted and analyzed by bioinformatics. The qPCR results showed that the expression trends of oar-miR-21, oar-miR-10b, oar-let-7f, oar-let-7b, and oar-miR-221 were consistent with the sequencing results. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes results showed that differentially expressed miRNAs were mainly involved in the immune system processes of the Arf6 downstream pathway. The target genes Reactome pathways were mainly enriched in the RAC1 GTPase cycle, CDC42 GTPase cycle, RHO GTPase cycle, RHOV GTPase cycle, and post-transcriptional silencing of small RNAs. The transcription factors SP4, NKX6-1, MEF2A, SP1, EGR1, and POU2F1 that may be connected to sheep pox virus (SPPV)-infected cells were discovered by transcription factor annotation screening. In conclusion, this study screened for differentially expressed miRNAs in SPPV-infected cells and performed a series of bioinformatic analyses of their target genes to provide a theoretical basis for the molecular mechanism of sheep pox virus infections of cells. The data can be used as basic information in future studies on the defense mechanisms against poxvirus infections.

Objective:To investigate the correlation between hearing loss and microvascular complications in diabetes.Methods:This cross-sectional study conducted the data from 572 patients with diabetes hospitalized in the Endocrinology Department of the General Hospital of Southern Theater Command from September 2022 to July 2023. All participants underwent electrical audiometry and acoustic immittance in the ENY department. Based on the audiometric results, participants were categorized into normal hearing group and hearing loss group. Additionally, 572 non-diabetic patients from the outpatient department were enrolled as the non-diabetic group. The general information and laboratory results were collected and compared using t test, rank sum test or χ2 test. Binary logistic regression analysis was used to evaluate the association of diabetic hearing loss with diabetic kidney disease(DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Results:Among 572 patients with diabetes, 429 suffered from hearing loss and 143 were normal. χ2 test showed significant differences in combined DKD and DPN between two groups, but not in DR. Multivariate binary logistic regression analysis identified DKD and DPN as risk factors for hearing loss, but no correlation was found with DR. Conclusion:Diabetic patients with DKD or DPN should be monitored for potential hearing loss. Early screening and treatment are crucial to prevent severe hearing impairment.

Sheep pox is widespread worldwide and is the most severe animal pox virus infection. This study aimed to identify the key microRNAs (miRNAs) differentially expressed in the exosomes of sheep poxvirus-infected cells and their target genes and related pathways and provide a theoretical basis for an in-depth understanding of the molecular mechanisms of sheep poxvirus-infected cells. In this study, the differentially expressed miRNAs were verified by quantitative polymerase chain reaction (qPCR), and the target genes of miRNAs were predicted and analyzed by bioinformatics. The qPCR results showed that the expression trends of oar-miR-21, oar-miR-10b, oar-let-7f, oar-let-7b, and oar-miR-221 were consistent with the sequencing results. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes results showed that differentially expressed miRNAs were mainly involved in the immune system processes of the Arf6 downstream pathway. The target genes Reactome pathways were mainly enriched in the RAC1 GTPase cycle, CDC42 GTPase cycle, RHO GTPase cycle, RHOV GTPase cycle, and post-transcriptional silencing of small RNAs. The transcription factors SP4, NKX6-1, MEF2A, SP1, EGR1, and POU2F1 that may be connected to sheep pox virus (SPPV)-infected cells were discovered by transcription factor annotation screening. In conclusion, this study screened for differentially expressed miRNAs in SPPV-infected cells and performed a series of bioinformatic analyses of their target genes to provide a theoretical basis for the molecular mechanism of sheep pox virus infections of cells. The data can be used as basic information in future studies on the defense mechanisms against poxvirus infections.