ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

Researchers commonly use cyclization recombination enzyme/locus of X-over P1 (Cre/loxP) technology-based conditional gene knockouts of model mice to investigate the functional roles of genes of interest in Sertoli and Leydig cells within the testis. However, the shortcomings of these genetic tools include high costs, lengthy experimental periods, and limited accessibility for researchers. Therefore, exploring alternative gene silencing techniques is of great practical value. In this study, we employed adeno-associated virus (AAV) as a vector for gene silencing in Sertoli and Leydig cells. Our findings demonstrated that AAV serotypes 1, 8, and 9 exhibited high infection efficiency in both types of testis cells. Importantly, we discovered that all three AAV serotypes exhibited exquisite specificity in targeting Sertoli cells via tubular injection while demonstrating remarkable selectivity in targeting Leydig cells via interstitial injection. We achieved cell-specific knockouts of the steroidogenic acute regulatory ( Star ) and luteinizing hormone/human chorionic gonadotropin receptor (Lhcgr) genes in Leydig cells, but not in Sertoli cells, using AAV9-single guide RNA (sgRNA)-mediated gene editing in Rosa26-LSL-Cas9 mice. Knockdown of androgen receptor ( Ar ) gene expression in Sertoli cells of wild-type mice was achieved via tubular injection of AAV9-short hairpin RNA (shRNA)-mediated targeting. Our findings offer technical approaches for investigating gene function in Sertoli and Leydig cells through AAV9-mediated gene silencing.
Animals ; Male ; Leydig Cells/metabolism* ; Mice ; Dependovirus/genetics* ; Sertoli Cells/metabolism* ; Gene Silencing ; Genetic Vectors ; Testis/cytology*

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Objective:To explore the incidence of chronic obstructive pulmonary disease (COPD) in a cohort aged 40 years and above in Songjiang District, Shanghai, and to analyze the association of Mediterranean diet pattern and dietary approaches in stopping hypertension pattern (DASH) with the risk of developing COPD.Methods:Based on a natural population cohort in Songjiang District, Shanghai, 27 474 adults aged 40 years and above who did not have COPD at baseline were enrolled in the study. The Cox proportional risk regression model was used to analyze the association of baseline Mediterranean diet pattern score and DASH score with the risk of COPD, and the hazard ratio ( HR) of the risk and its 95% CI were calculated. Restricted cubic spline was used to analyze the nonlinear association between the two diet scores and the risk of COPD. Stratified analyses were performed according to gender, age, smoking status, etcetera. Sensitivity analyses were conducted by censoring cases diagnosed within one year after the baseline survey or people with a history of malignant tumor disease. Results:As of June 30, 2023, after a median follow-up time of 6.21 years, there were 1 089 (4.0%) new COPD cases with an incidence density of 64.00 per 10 000 person-years. After adjusting for relevant confounders, in the Mediterranean tertile subgroups under diet pattern score, the risk of developing COPD could be reduced by approximately 14% in the intermediate scoring group ( HR=0.86, 95% CI: 0.75-0.99) and 15% in the highest scoring group ( HR=0.85, 95% CI: 0.72-0.99) compared to the lowest scoring group. The association remained after censoring cases diagnosed within one year of the baseline survey ( HR=0.82, 95% CI: 0.70-0.95; HR=0.82, 95% CI: 0.68-0.97) or censoring people with a history of malignant tumor disease ( HR=0.84, 95% CI: 0.73-0.97; HR=0.84, 95% CI: 0.71-0.99). No statistical association was found between the DASH score and the risk of COPD. Conclusions:The Mediterranean diet pattern was associated with a lower risk of COPD. Increasing the intake of vegetables, fruits, legumes, and whole grains and decreasing the intake of red meat and others can reduce the risk of COPD. No association was found between the DASH dietary pattern and the risk of COPD in this community population.

Objective To analyze Professor Zhang Binghou's medication experience in the treatment of diabetic kidney disease using data mining methods;To screen the core medicinal pairs and medicinal groups.Methods Prescriptions of diabetic kidney disease of Professor Zhang Binghou from the outpatient department of Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University were selected from January 2014 to December 2021.TCM Inheritance Platform System 2.5,SPSS Modeler 18 and SPSS Statistics 21 software were used for association rules,clustering analysis and factor analysis to summarize the medication frequency,properties and tastes and meridians,and medicinal pairs and combinations.Results A total of 161 prescriptions were included,involving 188 kinds of Chinese materia medica,with a total frequency of 2 220 time.The kinds of Chinese materia medica with higher frequency were Rehmannize Radix et Praeparata,Testudinis Carapax et Plastrum,Astragali Radix,Rehmannine Radix,etc.The main properties were cold and warm,the main tastes were sweet and bitter,and the main meridians were kidney,liver and spleen meridians.A total of 14 drug pair association rules were obtained,with 27 commonly used drug combinations.Clustering analysis extracted 10 combinations based on the spectrum,and factor analysis extracted 14 common factors.Conclusion Professor Zhang Binghou's treatment for diabetic kidney disease takes nourishing the true yin and clearing away damp-heat as the main treatment method,and at the same time,it pays attention to tonifying kidney,consolidating essence,nourishing yin and containing yang,promoting blood circulation and removing blood stasis,etc.,which embodies Professor Zhang Binghou's unique academic thought of treating diabetic kidney disease.

Carpal tunnel syndrome(CTS)is one of the most common peripheral nerve entrapment disorders,the elevated pressure in the carpal tunnel,high-intensity activities and obesity are the main causes,and the patients with mild to moderate CTS are more prevalent.The main pathogenesis of CTS involves the increasing of carpal tunnel pressure and impaired local blood oxygen supply leading to reduced nerve conduction.Currently,the clinical treatment methods for mild to moderate CTS mainly include surgical and nonsurgical treatments.Nonsurgical treatment is the preferable choice for the patients with mild to moderate CTS.The western medical treatment primarily rely on oral medications,but their long-term use is limited due to the certain adverse effects;the local blockade and extracorporeal shock wave therapies show better efficacy for the patients with frequent activities and severe symptoms;the traditional Chinese medicine treatment also becomes a choice for some CTS patients due to their advantages of less pain,lower medical costs,and significant effectiveness.This study reviews the recent advancements in the pathogenesis and treatment of mild to moderate CTS,in order to design the personalized treatment methods for the mild to moderate CTS patients based on their specific conditions in clinical settings and provide the references for precise treatment of the mild to moderate CTS patients.

Objective:To compare the safety of radial artery puncture in elderly patients aged 75 years and older who are undergoing neurointerventional procedures.Methods:A single-center retrospective study was conducted, involving 350 elderly patients aged 75 years and older who received neurointerventional treatment at Beijing Tiantan Hospital, Capital Medical University, from June to December 2022.The participants were divided into two groups based on the puncture site: femoral artery puncture and radial artery puncture.The safety indicators compared between the two groups included puncture failure, changes in puncture site, general puncture complications(such as subcutaneous bleeding, puncture site hematoma, and vasospasm), severe puncture complications(including distal limb ischemia and pseudoaneurysm), and lower limb venous thrombosis.Multivariate Logistic regression analysis was conducted to evaluate the impact of different puncture methods on the occurrence of complications.Results:Among the 350 patients, 280 underwent femoral artery puncture, while 70 underwent radial artery puncture.There were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The proportions of patients using antiplatelet drugs prior to surgery, puncture failure rates, rates of change in puncture sites, and the incidence of severe complications-including distal limb ischemia and pseudoaneurysm-were not significantly different between the two groups( χ2=2.051, 0.075, 0.588, 3.175; P=0.152, 0.784, 0.443, 0.075).In the femoral artery puncture group, 20.4%(57 cases)of patients experienced general puncture complications(including subcutaneous bleeding, puncture site hematoma, and vasospasm), whereas only 8.6%(6 cases)in the radial artery puncture group experienced such complications, revealing a statistically significant difference between the two groups( χ2=5.720, P=0.022).Multivariate Logistic regression analysis indicated that, compared to femoral artery puncture, radial artery puncture was associated with a reduced risk of all complications( OR=0.272, 95% CI: 0.139-0.532, P<0.001), general puncture complications( OR=0.375, 95% CI: 0.153-0.919, P=0.032)and lower limb venous thrombosis( OR=0.219, 95% CI: 0.050-0.954, P=0.043). Conclusions:In elderly patients aged 75 years and older who are undergoing neurointerventional procedures, radial artery puncture is associated with a reduced incidence of general puncture complications and lower limb venous thrombosis when compared to femoral artery puncture, indicating a superior safety profile.

Objectives:The purpose of this study was to investigate the clinical efficacy of percutaneous endoscopic transforaminal lumbar interbody fusion(PE-TLIF)in patients with single-segment lumbar spinal stenosis and explore the changes of paraspinal muscles and adjacent segmental facet joints of operative segement after PE-TLIF.Methods:28 patients with L4/5 lumbar spinal stenosis treated with PE-TLIF in Beijing Chaoyang Hospital from March 2017 to March 2019 were analyzed retrospectively.The patients consisted of 12 males and 16 females with an average age of 58.0±8.7 years(41-79 years)and were followed up for 40.7±3.6 months(36-58 months).The visual analogue scale(VAS)of low back pain(VAS-LBP)and VAS of leg pain(VAS-LP)were collected at pre-operation,postoperative 1-week follow-up,3-month follow-up,12-month follow-up and the final follow-up;Oswestry disability index(ODI)was evaluated at pre-operation,post-operative 3-month follow-up,12-month follow-up and the final follow-up.CT examination was performed at pre-operation,postoperative 12-month follow-up,24-month follow-up and the final follow-up,the cross-sec-tional area(CSA)and fat infiltration(FI)score of multifidus(MF)were measured,and the degeneration degree of adjacent segmental facet joints was evaluated according to the score of facet joint degeneration.The differ-ences of MF CSA and FI score,as well as adjacent segmental facet joint degeneration were compared be-tween preoperation and postoperation.Results:The VAS-LBP score was 3(2,3)at 1-week follow-up,1(1,2)at 3-month follow-up,1(0,2)at 12-month follow-up,and 1(0,1)at the final follow-up,which was signif-icantly improved compared with the preoperative score of 7(7,8)(P＜0.05);the VAS-LP score was 2(1,3)at 1-week follow-up,1(1,2)at 3-month follow-up,1(0,1)at 12-month follow-up,and 0(0,1)at the final fol-low-up,which were significantly improved compared with the preoperative score of 6(5,7)(P＜0.05);The ODI at 3-month follow-up was 23％(19％,31％),at 12-month follow-up was 12％(8.5％,17.5％),and at the final follow-up was 7％(4％,15.6％),all significantly improved compared with the ODI before operation of 61％(55％,67％)(P＜0.05).The postoperative MF CSAs of 547.12±53.31mm2(12-month follow-up),558.35±52.37mm2(24-month follow-up),and 531.21±56.12mm2(final follow-up)were not significantly changed from the preoper-ative MF CSA of 557.06±46.72mm2(P＞0.05).There was no significant difference in FI score between pre-op-eration of 2(2,3)and 12-month follow-up of 3(2,3),24-month follow-up of 3(2,3)and the final follow-up of 3(3,3)(P＞0.05).The postoperative facet joint degeneration scores of upper segment facet joint(USFJ)of 5(4,6)at 12-month follow-up,5(4,5)at 24-month follow-up,and 5(4,6)at final follow-up were not signifi-cantly changed from the preoperative 5(4,6)(P＞0.05).And there was no significant difference either in facet joint degeneration score of lower segment facet joint(LSFJ)between pre-operation of 5(4,6)and 12-month follow-up of 5(4,5),24-month follow-up of 5(4,6)and the final follow-up of 5(4,7)(P＞0.05).Conclusions:PE-TLIF can achieve satisfactory clinical outcomes in the treatment of single-segment lumbar spinal stenosis,which has no significant effect on multifidus in the surgical segment and adjacent segmental facet joints in the mid-to long-term.