ObjectiveTo investigate the mechanisms by which the combination of berberine （BBR） and baicalin （BAI） ameliorates type 2 diabetes mellitus （T2DM） due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group （n=10） and a T2DM （syndrome of internal accumulation of dampness-heat） fecal microbiota transplantation group （n=20）. The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage， respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group （n=8） and a BBR-BAI group （n=11）. BBR was administrated at a dose of 200 mg·kg^-1， and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， insulin （INS）， triglycerides （TG）， total cholesterol （CHOL）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1， zonula occludens-1 （ZO-1）， and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to assess the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）， respectively. ResultsThe BBR-BAI combination lowered the FBG， HbA1c， and INS levels （P<0.05， P<0.01） and alleviated insulin resistance （P<0.01） in T2DM mice. Additionally， BBR-BAI elevated the levels of ZO-1， occludin， and claudin-1 （P<0.05， P<0.01） and down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in the colon （P<0.05， P<0.01）. The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus， Phascolarctobacterium， and Akkermansia （P<0.05）， while significantly decreasing the relative abundance of Alistipes， Odoribacter， and Colidextribacter （P<0.05）. UPLC-Q-TOF-MS identified 28 differential metabolites， which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.

ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions， so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values（L^*） of the surface， cross-section and powder of the samples， texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography（HPLC） was used to determine the contents of seven nucleoside components（uracil， hypoxanthine， uridine， inosine， guanosine， β-thymidine and adenosine） in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis（PCA） was used to comprehensively rank the data of various indicators， and partial least squares-discriminant analysis（PLS-DA） was used to screen differential components with variable importance in the projection（VIP） value>1. Furthermore， the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature， the color of the intermittently dried samples gradually deepened， while their hardness gradually decreased. Concurrently， the contents of extract， total starch， uridine and adenosine exhibited an upward trend， whereas the contents of uracil， hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group， the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose， the hardness and the total content of nucleoside components in the samples showed a downward trend， while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L^* was negatively correlated with the contents of uracil， hypoxanthine and inosine， and positively correlated with the contents of uridine， guanosine and adenosine. Hardness was negatively correlated with adenosine content， and positively correlated with the contents of inosine， uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components， the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract， the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition， while uridine， uracil， guanosine， adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination， which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.

OBJECTIVE: To investigate the regulatory effect of electroacupuncture (EA) at "Neiguan" (PC6) on mitochondrial autophagy in rats with myocardial ischemia-reperfusion injury (MIRI) at different phases (ischemia and reperfusion phases), and to explore the bidirectional regulatory effects of EA at "Neiguan" (PC6) and its potential mechanism. METHODS: Forty-five male SD rats were randomly divided into 6 groups according to the random number table method, namely, sham-operation group (n=9), model-A group (n=6), model-B group (n=9), EA-A1 group (n=6), EA-B1 group (n=6), and EA-B2 group (n=9). Except the rats in the sham-operation group, the MIRI model was established in the other groups with the physical ligation and tube pushing method. In the model-A group, the samples were collected directly after ligation, and in the model-B group, the samples were collected after ligation and reperfusion. In the EA-A1 group, EA was delivered while the ligation was performed, and afterwards, the samples were collected. In the EA-B1 group, while the ligation was performed, EA was operated at the same time, and after reperfusion, the samples were collected. In the EA-B2 group, during ligation and the opening of the left anterior descending branch of the coronary artery, EA was delivered, and after reperfusion, the samples were collected. EA was performed at bilateral "Neiguan" (PC6), with a disperse-dense wave, a frequency of 2 Hz/100 Hz, a current of 1 mA, and a duration of 30 min. HE staining was employed to observe the morphology of cardiomyocytes, TUNEL was adopted to detect the apoptosis of cardiomyocytes, transcriptome sequencing was to detect the differentially expressed genes in the left ventricle, JC-1 flow cytometry was to detect the mitochondrial membrane potential (MMP) of cardiomyocytes, Western blot was to detect the protein expression of phosphatase and tensin homolog-induced kinase 1 (Pink1), Parkin and p62 in the left ventricle of rats, and ELISA was to detect the levels of serum creatine kinase isoenzyme (CK-MB) and cardiac troponin I (cTn-I) in the rats. RESULTS: Compared with the sham-operation group, the cardiomyocytes of rats in the model-B group were severely damaged, with disordered arrangement, unclear boundaries, broken muscle fibers, edema and loose distribution; and the cardiomyocytes in the EA-B2 group were slightly damaged, the cell structure was partially unclear, the cells were arranged more regularly, and the intact cardiomyocytes were visible. Compared with the sham-operation group, the apoptosis of cardiomyocytes increased in the model-B group (P<0.001); and when compared with the model-B group, the apoptosis alleviated in the EA-B2 group (P<0.001). The differentially expressed genes among the EA-B2 group, the sham-operation group and the model-B group were closely related to cell autophagy and mitochondrial autophagy. Compared with the sham-operation group, MMP of cardiomyocytes was reduced (P<0.001), the protein expression of Pink1, Parkin, and p62 of the left ventricle and the levels of serum CK-MB and cTn-I were elevated in the model B group (P<0.001). In comparison with model-A group, the MMP of cardiomyocytes and the levels of serum CK-MB and cTn-I were reduced (P<0.001, P<0.05), and the protein expression of Pink1 in the left ventricle rose in the EA-A1 group (P<0.01). Compared with the model-B group, MMP of cardiomyocytes increased (P<0.001), the protein expression of Pink1, Parkin, and p62 of the left ventricle, and the levels of serum CK-MB and cTn-I decreased (P<0.001) in the EA-B1 group and the EA-B2 group. When compared with the EA-A1 group, MMP of cardiomyocytes increased (P<0.001), and the protein expression of Pink1, Parkin, and p62 of the left ventricle, and the levels of serum CK-MB and cTn-I decreased in the EA-B1 group (P<0.01). CONCLUSION EA at "Neiguan" (PC6) can ameliorate MIRI in rats, which may be achieved through the Pink1/Parkin-mediated mitochondrial autophagy pathway. EA can alleviate myocardial injury by enhancing mitochondrial autophagy at the ischemia phase, and it can reduce reperfusion injury by weakening mitochondrial autophagy at the reperfusion phase.
Animals ; Electroacupuncture ; Male ; Myocardial Reperfusion Injury/metabolism* ; Rats, Sprague-Dawley ; Rats ; Acupuncture Points ; Autophagy ; Humans ; Mitochondria/genetics*

OBJECTIVES: To analyze the efficacy and safety of concomitant left atrial appendage clipping during heart valve surgery for valvular heart disease patients with atrial fibrillation. METHODS: Fifty-eight patients who underwent concomitant left atrial appendage clipping during cardiac valve surgery in the Second Affiliated Hospital of Nanchang University from January 2017 to June 2023 were included in the analysis, including 1 case who underwent aortic valve replacement, 49 cases who underwent mitral valve replace-ment (or valvuloplasty)+tricuspid valvuloplasty, and 8 cases who underwent double valve replacement+tricuspid valvuloplasty (3 cases combined with coronary artery bypass grafting). The patients were followed up for 3-36 months [(16.69±6.61) months] after operation, and the changes of cardiac function and the occurrence of serious adverse complications were evaluated. RESULTS: The cardiopulmonary bypass time ranged from 75 to 145 min [(102.50±21.03) min], and the aortic cross-clamp time ranged from 35 to 80 min [(58.02±14.63) min]. The length of postoperative intensive care unit stay was 1 to 5 days [(2.47±0.82) d], and the length of postoperative hospital stay was 7 to 22 days [(10.84±2.69) d]. Cardiac ultrasound indicated complete closure of the left atrial appendage in all cases. During the follow-up, New York Heart Association (NYHA) functional classifications were improved in 54 patients. No left atrial appendage-related bleeding events or other perioperative complications were observed; and no cerebral infarction, limb embolism events, or mortality cases occurred during the follow-up. CONCLUSIONS For valvular heart disease patients with atrial fibrillation, concomitant left atrial appendage clipping during cardiac valve surgery demonstrates efficacy and safety, with no severe adverse events during a medium-term follow-up.
Humans ; Atrial Appendage/surgery* ; Atrial Fibrillation/complications* ; Male ; Female ; Heart Valve Diseases/complications* ; Aged ; Middle Aged ; Heart Valve Prosthesis Implantation/methods* ; Treatment Outcome ; Cardiac Surgical Procedures/methods* ; Mitral Valve/surgery*

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Objective To explore the clinical value of the platelet count(PLT)to high-density lipoprotein cholesterol(HDL-C)ratio(PHR)in predicting poor prognosis after intravenous thrombolysis in patients with acute cerebral infarction(ACI).Methods A total of 304 patients with ACI who received intravenous thrombolytic therapy in this hospital from January 2021 to December 2023 were selected as the research sub-jects.According to the modified Rankin scale score at 6-month follow-up,the 304 patients with ACI were di-vided into the good prognosis group(n=216)and the poor prognosis group(n=88).Clinical data of all pa-tients were collected.The levels of PLT,HDL-C and PHR were compared between the two groups.The pre-dictive value of PLT,HDL-C and PHR for the prognosis of ACI patients was analyzed by using the receiver operating characteristic(ROC)curve.Binary Logistic stepwise regression analysis was used to explore the in-fluencing factors of prognosis in ACI patients.Results Compared with the good prognosis group,the HDL-C level in the poor prognosis group decreased,while the PLT level and PHR increased(P＜0.05).The results of the ROC curve showed that the area under the curve(AUC)and 95％CI of PLT,HDL-C,and PHR for pre-dicting poor prognosis after intravenous thrombolysis in ACI patients was 0.829(0.784-0.874),0.743(0.693-0.788),and 0.918(0.873-0.968),respectively.The AUC of PHR in predicting poor prognosis af-ter intravenous thrombolysis in ACI patients was higher than that of PLT and HDL-C alone(Z=13.239,10.776,P＜0.001).The proportions of National Institutes of Health Stroke Scale(NIHSS)score ≥8 points at admission,transformation of previous symptomatic hemorrhage,combined hypertension,and combined dia-betes in the poor prognosis group were all higher than those in the good prognosis group(P＜0.05).The re-sults of binary Logistic stepwise regression showed that the NIHSS score at admission(OR=2.565,95％CI:1.292-5.094),the transformation of previous symptomatic hemorrhage(OR=2.073,95％CI:1.179-8.645),and PHR(OR=3.732,95％CI:2.037-6.839)were risk factors for poor prognosis in ACI patients(P＜0.05).Conclusion PHR is expected to become an important reference index for predicting the prognosis of ACI patients after intravenous thrombolysis therapy.PHR,NIHSS score at admission,and the transforma-tion of previous symptomatic hemorrhage are all influencing factors for the prognosis of ACI patients after in-travenous thrombolysis therapy.

Objective:To investigate the correlation between the timing of minimally invasive puncture drainage and the outcome of patients with hypertensive intracerebral hemorrhage (HICH) in the basal ganglia region.Methods:Patients with HICH in the basal ganglia region underwent minimally invasive puncture and drainage at Hanchuan People's Hospital from January 2019 to September 2023 were selected. According to the timing of surgery, the patients were divided into onset to surgery time ≤12-hour group and >12-hour group. According to the modified Rankin Scale score at 90 days after onset, they were divided into a good outcome group (0-2) and a poor outcome group (>2). Multivariate logistic regression analysis was used to evaluate the independent influencing factors of functional outcome. Results:A total of 150 patients were included, with 78 males (52.00%), aged 53.15±4.35 years (range, 40-75 years). Eighty-six patients (57.33%) underwent surgery within 12 hours after onset, while 64 (42.67%) underwent surgery after 12 hours; 97 patients (64.67%) had good outcome, while 53 (35.33%) had poor outcome. Univariate analysis showed that compared with the onset to surgery time ≤12-hour group, the onset to surgery time >12-hour group had a longer time from onset to admission, a larger postoperative hematoma volume, longer hospitalization time, lower postoperative hematoma clearance rate, and a higher proportion of patients with poor outcome and deaths within 90 days (all P<0.05). Compared with the good outcome group, the poor outcome group had a longer time from onset to admission, higher baseline National Institutes of Health Stroke Scale (NIHSS) scores, larger baseline and postoperative hematoma volumes, and a higher proportion of patients with onset to surgery time >12 hours. However, the postoperative hematoma clearance rate, baseline Glasgow Coma Scale (GCS) score, and the proportion of patients with baseline GCS score >8 was lower in the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that the higher baseline NIHSS score (odds ratio [ OR] 1.847, 95% confidence interval [ CI] 1.362-2.503; P=0.001) and the time from onset to surgery >12 hours (compared with ≤12 hours: OR 1.347, 95% CI 1.058-1.715; P=0.016) were the independent risk factors for poor outcome, while higher baseline GCS scores ( OR 0.723, 95% CI 0.558-0.937; P=0.006) and higher postoperative hematoma clearance rates ( OR 0.615, 95% CI 0.462-0.819; P=0.004) were the independent protective factors for good outcome. Conclusion:In patients with HICH in basal ganglia, it is ideal to perform minimally invasive puncture and drainage within 12 h after onset, and the postoperative recovery is relatively better.

Objective To develop an instrument for predicting postoperative constipation risks in patients with osteoporotic thoracolumbar fracture(OTLF)who have undergone percutaneous kyphoplasty(PKP).Methods A total of 858 OTLF patients who underwent PKP surgery between January 2020 and December 2024 were enrolled.The patients were randomly assigned to a training set(n=600)and a validation set(n=258)in a 7∶3 ratio.According to whether the patients had postoperative constipation,the training set was divided into a constipation group(n=205)and a non-constipation group(n=395),and the validation set was divided into a constipation group(n=90)and a non-constipation group(n=168).Logistic regression analysis was conducted to analyze the factors influencing postoperative constipation in OTLF patients after PKP,and a nomogram model was constructed accordingly.The receiver operating characteristic(ROC)curve and the calibration curve of the model were plotted,and the Hosmer-Lemeshow test for goodness of fit was performed.Results A total of 205 OTLF patients(34.17%)in the training set and 90 OTLF patients(34.88%)in the validation set experienced constipation after PKP.Univariate analysis revealed significant differences between the constipation and non-constipation groups in terms of operative time,postoperative water intake,time to first postoperative meal,postoperative bed rest time,the levels of Bifidobacterium,Lactobacillus,Enterococcus,and Enterobacter,the Nutrition Risk Screening 2002(NRS-2002)score,and the levels of sodium,potassium,and HbA1c(P<0.05).Least absolute shrinkage and selection operator(LASSO)regression was performed and operative time,time to first postoperative meal,the levels of Bifidobacterium,Lactobacillus,Enterococcus,and Enterobacter,the NRS-2002 score,and the levels of sodium,potassium,and HbA1c were identified as candidate predictors.Multivariate logistic analysis showed that the time to first postoperative meal,the levels of Bifidobacterium and Lactobacillus,the NRS-2002 score,and the levels of sodium and HbA1c were influencing factors of postoperative constipation in OTLF patients(P<0.05).The ROC curves showed that the area under the curve(AUC)of the training set was 0.842(95%CI:0.793-0.892),while that of the validation set was 0.860(95%CI:0.830-0.889).The calibration curves demonstrated good agreement between the prediction curve and the standard curve in both the training set and the validation set.Conclusion The time to the first postoperative meal,the NRS2002 score,and the levels of Bifidobacterium,Lactobacillus,sodium,and HbA1c are influencing factors of post-PKP constipation in OTLF patients.The nomogram model built based on these factors exhibited good predictive performance.