ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

ObjectiveTo evaluate the clinical efficacy of Maxing Loushi decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease （AECOPD） with phlegm turbidity obstructing lung syndrome， and to investigate its effects on inflammatory factors， immune function， and the programmed death-1（PD-1）/programmed death-ligand 1 （PD-L1） signaling pathway. MethodsA randomized controlled study was conducted， enrolling 90 hospitalized patients with AECOPD and phlegm turbidity obstructing lung syndrome in the Respiratory and Emergency Departments of Dongzhimen Hospital， Beijing University of Chinese Medicine， from April 2024 to December 2024. Patients were randomly assigned to a control group and an observation group using a random number table， with 45 patients in each group. The control group received conventional Western medical treatment， while the observation group received additional Maxing Loushi decoction for 14 days. Clinical efficacy， COPD Assessment Test （CAT） score， modified Medical Research Council Dyspnea Scale （mMRC）， 6-minute walk test （6MWT）， serum inflammatory factors， T lymphocyte subsets， and serum PD-1/PD-L1 levels were compared between the two groups before and after treatment. ResultsThe total clinical effective rate was 78.57% （33/42） in the control group and 95.35% （41/43） in the observation group， with the observation group showing significantly higher efficacy than that of the control group. The difference was statistically significant （χ² = 5.136， P<0.05）. After treatment， both groups showed significant reductions in CAT and mMRC scores （P<0.05， P<0.01） and significant increases in 6MWT compared to baseline （P<0.01）. The observation group demonstrated significantly greater improvements than the control group in this regard. Levels of inflammatory markers including C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， monocyte chemoattractant protein-1（MCP-1）， and macrophage inflammatory protein-1α （MIP-1α） were significantly reduced in both groups （P<0.05， P<0.01）， with greater reductions in the observation group （P<0.05， P<0.01）. CD8⁺ levels were significantly reduced （P<0.01）， while CD3⁺， CD4⁺， and CD4⁺/CD8⁺ levels were significantly increased in both groups after treatment （P<0.05， P<0.01）， with more significant improvements observed in the observation group （P<0.05， P<0.01）. Serum PD-1 levels were reduced （P<0.05， P<0.01）， and PD-L1 levels were increased significantly in both groups after treatment （P<0.05， P<0.01）， with more pronounced changes in the observation group （P<0.05）. ConclusionMaxing Loushi decoction demonstrates definite therapeutic efficacy as an adjunctive treatment for patients with AECOPD and phlegm turbidity obstructing lung syndrome. It contributes to reducing serum inflammatory factors， improving immune function， and regulating the PD-1/PD-L1 signaling pathway.

ObjectiveTo evaluate the clinical efficacy of Maxing Loushi decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease （AECOPD） with phlegm turbidity obstructing lung syndrome， and to investigate its effects on inflammatory factors， immune function， and the programmed death-1（PD-1）/programmed death-ligand 1 （PD-L1） signaling pathway. MethodsA randomized controlled study was conducted， enrolling 90 hospitalized patients with AECOPD and phlegm turbidity obstructing lung syndrome in the Respiratory and Emergency Departments of Dongzhimen Hospital， Beijing University of Chinese Medicine， from April 2024 to December 2024. Patients were randomly assigned to a control group and an observation group using a random number table， with 45 patients in each group. The control group received conventional Western medical treatment， while the observation group received additional Maxing Loushi decoction for 14 days. Clinical efficacy， COPD Assessment Test （CAT） score， modified Medical Research Council Dyspnea Scale （mMRC）， 6-minute walk test （6MWT）， serum inflammatory factors， T lymphocyte subsets， and serum PD-1/PD-L1 levels were compared between the two groups before and after treatment. ResultsThe total clinical effective rate was 78.57% （33/42） in the control group and 95.35% （41/43） in the observation group， with the observation group showing significantly higher efficacy than that of the control group. The difference was statistically significant （χ² = 5.136， P<0.05）. After treatment， both groups showed significant reductions in CAT and mMRC scores （P<0.05， P<0.01） and significant increases in 6MWT compared to baseline （P<0.01）. The observation group demonstrated significantly greater improvements than the control group in this regard. Levels of inflammatory markers including C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， monocyte chemoattractant protein-1（MCP-1）， and macrophage inflammatory protein-1α （MIP-1α） were significantly reduced in both groups （P<0.05， P<0.01）， with greater reductions in the observation group （P<0.05， P<0.01）. CD8⁺ levels were significantly reduced （P<0.01）， while CD3⁺， CD4⁺， and CD4⁺/CD8⁺ levels were significantly increased in both groups after treatment （P<0.05， P<0.01）， with more significant improvements observed in the observation group （P<0.05， P<0.01）. Serum PD-1 levels were reduced （P<0.05， P<0.01）， and PD-L1 levels were increased significantly in both groups after treatment （P<0.05， P<0.01）， with more pronounced changes in the observation group （P<0.05）. ConclusionMaxing Loushi decoction demonstrates definite therapeutic efficacy as an adjunctive treatment for patients with AECOPD and phlegm turbidity obstructing lung syndrome. It contributes to reducing serum inflammatory factors， improving immune function， and regulating the PD-1/PD-L1 signaling pathway.

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

AIM To establish the near-infrared spectroscopy quantitative models for moisture,23-acetylalismol B and 23-acetylalismol C in Alismatis Rhizoma decoction pieces.METHODS The near-infrared spectroscopy(NIRS)data were collected in 95 batches of decoction pieces,after which drying method was adopted in the content determination of moisture,HPLC was applied to determining the contents of 23-acetylalismol B and 23-acetylalismol C,the quantitative models were established by partial least squares method combined with feature extraction algorithms.RESULTS The model training determination coefficients were 0.952 6,0.958 1 and 0.920 8,along with the prediction determination coefficients of 0.930 0,0.905 2 and 0.906 4,the residual prediction deviations(PRD)of 4.00,3.58 and 3.46,and the root mean square error ratios of prediction values to calibration values(RMSEP/RMSEC)of 1.15,1.11 and 1.06,respectively.CONCLUSION The quantitative models based on NIRS exhibit good prediction effects,which can be used for the rapid quality detection of Alismatis Rhizoma decoction pieces.

AIM To establish the near-infrared spectroscopy quantitative models for moisture,23-acetylalismol B and 23-acetylalismol C in Alismatis Rhizoma decoction pieces.METHODS The near-infrared spectroscopy(NIRS)data were collected in 95 batches of decoction pieces,after which drying method was adopted in the content determination of moisture,HPLC was applied to determining the contents of 23-acetylalismol B and 23-acetylalismol C,the quantitative models were established by partial least squares method combined with feature extraction algorithms.RESULTS The model training determination coefficients were 0.952 6,0.958 1 and 0.920 8,along with the prediction determination coefficients of 0.930 0,0.905 2 and 0.906 4,the residual prediction deviations(PRD)of 4.00,3.58 and 3.46,and the root mean square error ratios of prediction values to calibration values(RMSEP/RMSEC)of 1.15,1.11 and 1.06,respectively.CONCLUSION The quantitative models based on NIRS exhibit good prediction effects,which can be used for the rapid quality detection of Alismatis Rhizoma decoction pieces.

Objective To retrospectively analyze the ultra-fast track anesthesia(UFTA)methods and perioperative anesthesia management experiences of transcatheter mitral valve edge-to-edge repair(TEER)in the treatment of functional mitral regurgitant.Methods In this retrospective study,patients underwent the TEER procedure and received UFTA in Fuwai Yunnan Hospital,from May 2022 to September 2022 for heart failure combined with moderate to severe or severe functional mitral regurgitant were included.Baseline,preoperative complications,cardial function and anesthesia classification,amino-terminal probrain natriuretic peptide(NT-proBNP),ultrasound examination results,surgery time,extubation time,intraoperative anesthetic and vasoactive drug,complications related to TEER and UFTA,perioperative,and postoperative 30-day and one-year follow-up data were collected.All perioperative clinical data were recorded and analyzed.Results A total of 30 patients were enrolled,11 patients(36.7％)were female,mean age was(63.6±6.1)years,NYHA classification IV 14 patients(46.7％),left ventricular ejection fraction(LVEF)(36.0±8.1)％,the end-diastolic volume of the left ventricle(66.0±8.2)mm,mitral regurgitation 4+14 patients(56.7％),3+17 patients(43.3％),NT-proBNP(1 934.1±1 973.5)pg/ml,1 patient(3.3％)used high-dose vasoactive drugs during surgery.All patients did not experience nausea,vomiting,delirium,respiratory depression,perioperative transesophageal echocardiography-related gastrointestinal bleeding,pericardial effusion,cerebrovascular accidents,emergency surgery or secondary intervention,or other serious adverse events within 24 hours after surgery.No 30-day all-cause death occurred;the mean postoperative hospital stay was(7.4±2.8)days.All patients completed one-year follow-up,LVEF(37.6±11.1)％,the end-diastolic volume of the left ventricle(63.2±8.6)mm,mitral regurgitation 2+7 patients(23.3％),1+23 patients(76.7％),NT-proBNP(1 949.2±2 576.6)pg/ml.Conclusions Ultra-fast track anesthesia can be safely applied to TEER in treating functional mitral regurgitant patients.