Based on the α7 nicotinic acetylcholine receptor(α7nAChR), this study examined how tetrahydropalmatine(THP) affected BV2 microglia exposed to lipopolysaccharide(LPS), aiming to clarify the possible mechanism underlying the anti-depression effect of THP from the perspectives of preventing inflammation and regulating polarization. First, after molecular docking and determination of the content of Corydalis saxicola Bunting total alkaloids, THP was initially identified as a possible anti-depression component. The BV2 microglia model of inflammation was established with LPS. BV2 microglia were allocated into a normal group, a model group, low-and high-dose(20 and 40 μmol·L~(-1), respectively) THP groups, and a THP(20 μmol·L~(-1))+α7nAChR-specific antagonist MLA(1 μmol·L~(-1)) group. The CCK-8 assay was used to screen the safe concentration of THP. A light microscope was used to examine the morphology of the cells. Western blot and immunofluorescence were used to determine the expression of α7nAChR. qRT-PCR was performed to determine the mRNA levels of inducible nitric oxide synthase(iNOS), cluster of differentiation 86(CD86), suppressor of cytokine signaling 3(SOCS3), arginase-1(Arg-1), cluster of differentiation 206(CD206), tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. The experimental results showed that THP at concentrations of 40 μmol·L~(-1) and below had no effect on BV2 microglia. THP improved the morphology of BV2 microglia, significantly up-regulated the protein level of α7nAChR, significantly down-regulated the mRNA levels of iNOS, CD86, SOCS3, TNF-α, IL-6, and IL-1β, significantly up-regulated the mRNA levels of Arg-1 and CD206, and dramatically lowered the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. However, the antagonist MLA abolished the above-mentioned ameliorative effects of THP on LPS-treated BV2 microglia. As demonstrated by the aforementioned findings, THP protected LPS-treated BV2 microglia by regulating the M1/M2 polarization and preventing inflammation, which might be connected to the regulation of α7nAChR on BV2 microglia.
Berberine Alkaloids/chemistry* ; alpha7 Nicotinic Acetylcholine Receptor/chemistry* ; Microglia/metabolism* ; Mice ; Animals ; Cell Line ; Corydalis/chemistry* ; Humans ; Molecular Docking Simulation ; Inflammation/drug therapy* ; Nitric Oxide Synthase Type II/immunology* ; Tumor Necrosis Factor-alpha/immunology*

Objective To investigate the value of repeat renal biopsy in the treatment and prognosis of nephrotic syndrome(NS)and acute kidney injury(AKI)following immunosuppressive therapy in patients with lupus nephritis(LN). Methods A retrospective analysis was conducted for the clinicopathological data and follow-up records of LN patients undergoing repeat renal biopsy at Peking Union Medical College Hospital from January 1,2009 to December 31,2021. Results A total of 76 patients(55 females,72.4%)were included in this study,with the mean age at the first biopsy being(29.0±10.4)years,the median inter-biopsy interval of 4.0(2.0,7.0) years,and the median total follow-up duration of 7.5(5.0,13.8)years.Pathological transformation occurred in 46(60.5%)patients,and 2 patients had comorbid diabetic nephropathy.At repeat renal biopsy,50(65.8%) patients presented NS.These patients demonstrated lower estimated glomerular filtration rate(eGFR)(P<0.001),higher chronicity index(CI)(P=0.029),and higher complement C3(P<0.001)and C4(P<0.001)levels than those with NS at the first renal biopsy(n=50).Among the 28(36.8%) patients with AKI at repeat renal biopsy,8(28.6%)experienced acute exacerbation of chronic renal insufficiency.These patients exhibited higher serum creatinine level(P=0.002),C4 level(P=0.033),CI(P=0.042),and prevalence of thrombotic microangiopathy(P=0.046)than the patients showing AKI at the first renal biopsy(n=16),while the activity index(AI)showed no significant difference(P=0.051).Over 50% of NS and AKI patients underwent treatment modifications post-repeat renal biopsy,with clinical remission rates comparable to those after the first renal biopsy(both P>0.05).Elevated CI(≥5,P=0.001)and serum creatinine(≥140 μmol/L,P<0.001)at repeat renal biopsy were identified as independent risk factors for poor prognosis.The patients with AKI at repeat renal biopsy had higher incidence of endpoint events than the non-AKI patients(P=0.015).Neither AKI at the first renal biopsy nor NS at both biopsies had significant associations with prognosis. Conclusions Repeat renal biopsy reveals not only sustained high disease activity but also accelerates chronic progression in LN patients,which underscore its critical role in guiding the therapy for severe LN post-immunosuppression.AKI,CI≥5,and serum creatinine ≥140 μmol/L at repeat renal biopsy are strongly associated with poor prognosis.
Humans ; Lupus Nephritis/drug therapy* ; Female ; Retrospective Studies ; Adult ; Male ; Prognosis ; Biopsy ; Kidney/pathology* ; Acute Kidney Injury/pathology* ; Nephrotic Syndrome/pathology* ; Glomerular Filtration Rate ; Young Adult ; Immunosuppressive Agents/therapeutic use* ; Middle Aged

AIM To study the chemical constituents from the stems and leaves of Dendrobium formosum Roxb.ex Lindl.and their biological activities.METHODS The 95％ethanol extract from the stems and leaves of D.formosum was isolated and purified by silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their inhibitory activities onα-glucosidase were determined by PNPG method,and their in vitro anti-inflammatory activities were evaluated by RAW264.7 model.RESULTS Fifteen compounds were isolated and identified as coniferyl p-coumarate(1),(-)-pinoresinol(2),2,5,7-trihydroxy-4-methoxy-9,10-dihydrophenanthrene(3),naringenin(4),spiropreussomerin A(5),7-hydroxy-14-de-O-methyl-lasiodiplodin(6),(4S,5S,6Z,8E)-5-hydroxydeca-6,8-dien-4-olide(7),(6S,9R)-blumenol C(8),p-hydroxybenzoic acid(9),m-hydroxybenzoic acid(10),p-hydroxy benzenepropanoic acid(11),5,7-dihydroxy-isobenzofuran(12),2-(4-hydroxyphenyl)-ethanol(13),β-sitostenone(14),β-sitosterol(15).The IC50 values of compounds 1 and 4 on α-glucosidase inhibition were(65.60±3.31)and(98.95±2.53)μmol/L,respectively.Compound 3 presented inhibitory activity on NO production in RAW 264.7 cells,with IC50 value of(3.97±0.12)μmol/L.CONCLUSION Compounds 5-6,8 and 12 are isolated from Orchidacae family for the first time,and 2-15 are first isolated from this plant.Compounds 1 and 4 have α-glucosidase inhibitory activities,and 3 has anti-inflammatory activity.

The epidemiological and spatiotemporal clustering characteristics of dengue fever in Fujian Province were ana-lyzed,to provide a scientific basis for dengue fever prevention and control.Descriptive epidemiology,spatial autocorrelation a-nalysis,and spatiotemporal scanning were used to analyze dengue fever cases in Fujian Province from 2011 to 2023.In this peri-od,a total of 3 586 cases of dengue fever were reported in Fujian Province,including 2 360 local cases,1 134 imported cases from abroad,and 92 imported cases from China.Cases were reported in ten prefectures and cities of the province,and 81 out of 88 counties reported cases.Imported cases were reported throughout the year in Fujian Province,but the occurrence of local ca-ses showed clear seasonality.Local cases and domestic imports were concentrated in August to October,whereas overseas im-ports occurred primarily from June to October.The imported cases were mainly from Southeast Asian countries,but a trend of spreading from Southeast Asian countries to South Asia,Africa,the Americas,and other regions,was observed.Spatio-tem-poral clustering of dengue fever was found in Fujian Province(Moran's I value 0.14-0.66,P＜0.05),and the high-high ag-gregation areas were distributed primarily in Fuzhou,Quanzhou,and Putian.Spatio-temporal scanning detected three aggrega-tion areas:one main and two secondary.The aggregation time was from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.The distribution of dengue fever in Fujian Province showed clear spatial and temporal clustering from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.For high concentration areas,national health campaigns,mosquito prevention and control,epidemic surveillance,medical personnel training,and other relevant measures could be carried out in advance before local cases appear every year.Reduce local transmission of dengue fever due to importation.

Objective To investigate the effects of different administration times on the efficacy and safety of subcutaneous immunotherapy using dual mite extracts in patients with allergic rhinitis(AR).Methods This study was designed as a retrospective cohort analysis.Thirty-nine mite-sensitized AR patients who completed three years of standardized dual-mite subcutaneous immunotherapy(SCIT)were included.Based on self-selected and consistently maintained injection schedules,patients were non-randomly assigned to either a morning dosing group(MD group,8:00-12:00,n=19)or an afternoon dosing group(AD group,14:00-18:00,n=20),with further subgroup stratification conducted at 2-hour intervals.Nasal and ocular symptoms were evaluated before and after treatment using the visual analog scale(VAS),and all adverse reactions were systematically recorded.Results The AD group exhibited significantly greater improvement in nasal itching compared to the MD group(median difference:-2 vs.0,U=118.5,P=0.04,effect size r=0.33).The AD group also demonstrated favorable trends toward improved sneezing,nasal congestion,rhinorrhea,and total VAS score,although these differences did not reach statistical significance.In the subgroup analysis by 2-hour intervals,the 16:00-18:00 subgroup showed greater symptom relief than the 8:00-10:00 subgroup,though the difference was not statistically significant.No significant differences were observed between the two groups in the incidence of total,local,or systemic adverse reactions(P>0.05),and no moderate or severe systemic adverse events occurred.Conclusions This preliminary retrospective analysis indicates that afternoon administration of dual-mite SCIT,particularly between 16:00 and 18:00,may enhance the improvement of nasal symptoms without elevating safety concerns.The timing of SCIT administration could therefore represent a promising avenue for treatment optimization.

Objective:To investigate the clinical efficacy of compound sabal berry tablets on overactive bladder symptoms in patients with benign prostatic hyperplasia after transurethral laser enucleation of the prostate.Methods:This study was a prospective study. Eighty patients with benign prostatic hyperplasia who underwent laser enucleation at Tongliao People's Hospital from January 2024 to December 2024 were included in this study. The patients were randomly divided into a study group and a control group using the random number table method, with 40 patients per group. The control group received 0.2 mg of tolterodine tartrate tablets twice a day after surgery. The study group was given compound sabal berry tablets (0.5 g orally three times a day) in addition to the treatment provided to the control group. Both groups of patients were treated for 4 weeks after surgery. The clinical efficacy of the two groups was compared, including the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), Maximum Postoperative Urinary Flow Rate (Qmax), Post-Void Residual (PVR), and the incidence of postoperative bladder irritative symptoms.Results:The differences in the preoperative indicators, including IPSS, OABSS, Qmax, and PVR, between the two groups were not statistically significant (all P > 0.05). Preoperatively, in the control group, Qmax was (8.64 ± 2.83) mL/s, IPSS was (25.10 ± 4.37), OABSS was (10.52 ± 1.87), and PVR was (80.70 ± 6.34) mL; in the study group, the respective values were (9.12 ± 2.95) mL/s, (24.60 ± 4.53), (10.83 ± 1.73), and (80.10 ± 5.61) mL. Postoperatively, in the control group, Qmax was (20.30 ± 3.65) mL/s, IPSS was (8.50 ± 1.58), OABSS was (4.09 ± 0.52), and PVR was (9.70 ± 2.48) mL, while in the study group, the respective values were (21.40 ± 4.38) mL/s, (7.40 ± 1.76), (1.71 ± 0.36), and (9.00 ± 1.75) mL. Postoperatively, both groups showed a significant increase in Qmax, while IPSS, OABSS, and PVR all significantly decreased (all P < 0.05). Postoperatively, the IPSS and OABSS in the study group were significantly lower than those in the control group ( t = -3.28, -25.89, both P < 0.05). However, there were no statistically significant differences in Qmax and PVR between the two groups (both P > 0.05). The incidence of bladder irritative symptoms in the study group [12.50% (5/40)] was significantly lower than that in the control group [35.00% (14/40), χ2 = 8.64, P < 0.05]. Conclusions:Compound sabal berry tablets can reduce postoperative prostate symptoms and overactive bladder symptoms in patients undergoing transurethral laser enucleation of the prostate for benign prostatic hyperplasia, demonstrating a certain clinical efficacy.

Transfer-RNA derived small RNA(tsRNA),a re-cently discovered class of non-coding RNA,is produced by ma-ture tRNA or tRNA precursor through the mediation of specific endonucleases.By regulating gene expression at the transcrip-tional and post transcriptional levels and acting as an epigenetic regulator,tsRNA plays an important role in the physiological and pathological processes of many organisms.Therefore,it has gradually become a research hotspot in biomedicine and attracted widespread attention.Moreover,there is increasing evidence that tsRNA is involved in the occurrence and development of many neuropsychiatric diseases through participating in stress re-sponse,cell proliferation and apoptosis,neural development,synaptic plasticity,neuroinflammation and immune regulation,epigenetic regulation,RNA processing,and protein translation regulation.This article mainly discusses the generation,classifi-cation and biological functions of tsRNA,and elaborates on the role and possible mechanisms of tsRNA in neurodevelopment and neuropsychiatric disorders,thereby further revealing the poten-tial of tsRNA as a reliable biomarker and therapeutic target for neuropsychiatric disorders.

Although percutaneous pulmonary artery denervation (PADN) has demonstrated long-term benefits in combined post- and pre-capillary pulmonary hypertension, its usefulness for isolated post-capillary pulmonary hypertension (IpcPH) remains unclear. This report presents 2 cases of IpcPH due to left heart failure who underwent PADN treatment following an insufficient response to optimized conventional therapy. This case study illustrates how PADN, when combined with heart failure guideline-directed medical therapy, may represent a promising treatment option for IpcPH.

Objective:Using methylation characteristics of human genes to construct machine learning predictive models for screening cervical cancer and precancerous lesions.Methods:Human DNA methylation detection was performed on 224 cervical exfoliated cell specimens from the Cancer Hospital of the Chinese Academy of Medical Sciences, Tianjin Central Hospital of Gynecology Obstetrics, Xinmi Maternal and Child Health Hospital of Henan Province, West China Second Affiliated Hospital of Sichuan University, and Heping Hospital Affiliated to Changzhi Medical College collected during April 2014 and March 2015. The hypermethylated gene fragments related to cervical cancer were selected by high-density, high-association, and hypermethylated gene fragment screening and the LASSO regression algorithm. Taking cervical intraepithelial neoplasia grade 2 (CIN2) or more severe lesions as the research outcome, machine learning predictive models based on the random forest (RF), naive Bayes (NB), and support vector machine (SVM) algorithm, respectively, were constructed. A total of 144 outpatient specimens were used as the training set and 80 cervical exfoliated cell specimens from women participating in the cervical cancer screening program were used as the test set to verify the predictive models. Using histological diagnosis results as the gold standard, the detection efficacy for CIN2 or more severe lesions of the three machine learning predictive models were compared with that of the human papilloma virus (HPV) detection and cytological diagnosis.Results:In the training set of 144 cases, there were 34 cases of HPV positivity, with a positive rate of 23.61%. Cytologically, there were 37 cases diagnosed as no intraepithelial lesion or malignancy (NILM), and 107 cases diagnosed as atypical squamous cells of undetermined significance (ASC-US) or above. Histologically, there were 28 cases without cervical intraepithelial neoplasia or benign cervical lesions, 31 cases of CIN1, 18 cases of CIN2, 31 cases of CIN3, and 36 cases of squamous cell carcinoma. Seven hypermethylated gene fragments were selected from 45 genes, and three machine learning prediction models based on the RF, NB, and SVM algorithm, respectively, were constructed. In the validation set of 80 cases, there were 28 cases of HPV positivity, with a positive rate of 35.00%. Cytologically, there were 65 cases diagnosed as NILM and 15 cases as ASC-US or above. Histologically, there were 39 cases without cervical intraepithelial neoplasia or benign cervical lesions, 10 cases of CIN1, 10 cases of CIN2, 11 cases of CIN3, and 10 cases of squamous cell carcinoma. In the validation set, the area under the curve (AUC) values of the RF model, NB model, SVM model, HPV detection, and cytological diagnosis of CIN2 or above were 0.90, 0.88, 0.82, 0.68, and 0.45, respectively. The DeLong test showed that there was no statistically significant difference in the AUC values between the RF, NB, and SVM models (all P＞0.05), and the AUC values of the RF and NB models were higher than that of HPV detection (both P＜0.01), and the AUC values of the RF, NB, and SVM models were higher than that of cytological diagnosis (all P＜0.01). Compared with the NB model, the sensitivity of the RF model was similar (80.65% vs. 77.42%), but the specificity of the NB model was much higher than that of the RF model (93.88% vs. 73.47%). Conclusion:Among the machine learning prediction models for cervical cancer and precancerous lesions constructed based on human DNA methylation, the NB model has good predictive performance for CIN2 and above lesions, and may be used for screening of cervical cancer and precancerous lesions.

The epidemiological and spatiotemporal clustering characteristics of dengue fever in Fujian Province were ana-lyzed,to provide a scientific basis for dengue fever prevention and control.Descriptive epidemiology,spatial autocorrelation a-nalysis,and spatiotemporal scanning were used to analyze dengue fever cases in Fujian Province from 2011 to 2023.In this peri-od,a total of 3 586 cases of dengue fever were reported in Fujian Province,including 2 360 local cases,1 134 imported cases from abroad,and 92 imported cases from China.Cases were reported in ten prefectures and cities of the province,and 81 out of 88 counties reported cases.Imported cases were reported throughout the year in Fujian Province,but the occurrence of local ca-ses showed clear seasonality.Local cases and domestic imports were concentrated in August to October,whereas overseas im-ports occurred primarily from June to October.The imported cases were mainly from Southeast Asian countries,but a trend of spreading from Southeast Asian countries to South Asia,Africa,the Americas,and other regions,was observed.Spatio-tem-poral clustering of dengue fever was found in Fujian Province(Moran's I value 0.14-0.66,P＜0.05),and the high-high ag-gregation areas were distributed primarily in Fuzhou,Quanzhou,and Putian.Spatio-temporal scanning detected three aggrega-tion areas:one main and two secondary.The aggregation time was from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.The distribution of dengue fever in Fujian Province showed clear spatial and temporal clustering from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.For high concentration areas,national health campaigns,mosquito prevention and control,epidemic surveillance,medical personnel training,and other relevant measures could be carried out in advance before local cases appear every year.Reduce local transmission of dengue fever due to importation.