This paper aimed to explore the effects of Duzhong Decoction(DZD)-containing serum on the proliferation and osteoblast differentiation of MC3T3-E1 cells through L-type voltage-gated calcium channels(L-VGCCs). L-VGCCs inhibitors, nifedipine and verapamil, were used to block L-VGCCs in osteoblasts. MC3T3-E1 cells were divided into a control group, a low-dose DZD-containing serum(L-DZD) group, a medium-dose DZD-containing serum(M-DZD) group, a high-dose DZD-containing serum(H-DZD) group, a nifedipine group, a H-DZD + nifedipine group, verapamil group, and a H-DZD + verapamil group. The CCK-8 method was used for cell proliferation analysis, alkaline phosphatase(ALP) assay kits for intracellular ALP activity measurement, Western blot for protein expression level in cells, real-time fluorescence quantitative PCR technology for intracellular mRNA expression level determination, fluorescence spectrophotometer for free Ca~(2+) concentration determination in osteoblasts, and alizarin red staining(ARS) for mineralized nodule formation in osteoblasts. The experimental results show that compared to the control group, DZD groups can promote MC3T3-E1 cell proliferation, ALP activity, and mineralized nodule formation, increase intracellular Ca~(2+) concentrations, and upregulate the protein expression of bone morphogenetic protein 2(BMP2), collagen Ⅰ(COL1), α2 subunit protein of L-VGCCs(L-VGCCα2), and the mRNA expression of Runt-related transcription factor 2(RUNX2), and BMP2. After blocking L-VGCCs with nifedipine and verapamil, the intervention effects of DZD-containing serum were inhibited to varying degrees. Both nifedipine and verapamil could inhibit ALP activity, reduce mineralized nodule areas, and downregulate the expression of bone formation-related proteins. Moreover, the effects of DZD-containing serum on increasing MC3T3-E1 cell proliferation, osteoblast differentiation, and Ca~(2+) concentrations, upregulating the mRNA expression of osteoprotegerin(OPG) and protein expression of phosphorylated protein kinase B(p-Akt) and phosphorylated forkhead box protein O1(p-FOXO1), and upregulating phosphatase and tensin homolog(PTEN) expression were reversed by nifedipine. The results indicate that DZD-containing serum can increase the Ca~(2+) concentration in MC3T3-E1 cells to promote bone formation, which may be mediated by L-VGCCs and the PTEN/Akt/FoxO1 signaling pathway, providing a new perspective on the mechanism of DZD in treating osteoporosis.
Animals ; Osteoblasts/metabolism* ; Cell Proliferation/drug effects* ; Cell Differentiation/drug effects* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Calcium Channels, L-Type/genetics* ; Alkaline Phosphatase/genetics* ; Serum/chemistry* ; Cell Line ; Osteogenesis/drug effects* ; Bone Morphogenetic Protein 2/genetics*

Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans ; Obesity/therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: The aim of this study is to explore the clinical efficacy and safety of endocrinotherapy combined with Shenqi Pills on hormone-sensitive prostate cancer (HSPC). METHODS: Eighty patients who were diagnosed with HSPC and renal-yang deficiency at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine and the Hospital of Traditional Chinese Medicine of Mayang Miao Autonomous County from 1st April 2021 to 30th April 2024 were randomly divided into 2 groups. The patients in the control group were treated with androgen deprivation therapy (ADT). And the patients in treatment group were treated with Shenqi Pills orally on the basis of the control group. The baseline data of the two groups were analyzed. After 36 months of treatment, the differences between the two groups were compared in terms of overall survival (OS), prostate-specific antigen (PSA) level, PSA response rate, Functional Assessment Scale for Prostate Cancer Therapy (FACT-P), Chinese medicine evidence scores, testosterone level and safety. RESULTS: A total of 80 study subjects were included in this study, including 42 cases in the treatment group and 38 cases in the control group. There was no statistical difference in the baseline data between the two groups before treatment (P>0.05). At the end of the observation period, a statistically significant difference in OS was found in the treatment group compared to the control group in the subgroup of patients with a disease duration ranged of 0-6 months (P<0.05). There was no statistically significant difference in PSA levels in the treatment group at 3 months (P>0.05). And the differences in the proportion of PSA50 (98.1% vs 91.4%), PSA90 (92.9% vs 84.6%) and the proportion of decrease in PSA (56.7% vs 33.8%) in the treatment group were found compared to those in the control group after 6 months of tre atment. After 12 months of treatment, the scores of FACT-4 and renal-yang deficiency in the treatment group were (95.28±7.93) and (15.73±5.70) respectively, compared to the scores in the control group (［85.46±10.12］ and ［18.20±4.27］ (P<0.05). However, there was no significant difference in serum testosterone (［0.60±0.24］ nmol/L vs ［1.09±2.10］ nmol/L) between the two groups (P>0.05). After 24 months of treatment, there were significant differences in in the FACT-4 total score (［97.95±7.54］ vs ［80.33±8.58］), renal-yang deficiency syndrome score (［14.64±5.15］ vs ［24.94±8.75］) between the treatment group and the control group (P<0.05). However, there was no significant difference in serum testosterone ( ［0.73±1.01］ nmol/L vs ［0.59±0.25］ nmol/L) between the two groups (P> 0.05). Better therapeutic results were showed in the treatment group in terms of total FACT-P score, physical situation score, social and family situation score, emotional state score, functional state score, additional score and renal-yang deficiency symptom score (P<0.05). After treatment, there was no serious adverse reaction in the course of treatment, and no obvious abnormality was found in the liver and kidney function of the patients from two groups. CONCLUSION Endocrinotherapy combined with Shenqi Pills is safe and effective in HSPC and can reduce the risk of death in HSPC patients, and the earlier the intervention, the longer the overall survival of the patients. In addition, this treatment regimen can increase the PSA response rate, improve patients' quality of life, and reduce the renal-yang deficiency syndrome score without the risk of elevating serum testosterone levels.
Humans ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Prostatic Neoplasms/drug therapy* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged ; Treatment Outcome ; Testosterone

Objective To compare the clinical efficacies of video-assisted thoracoscopic segmentectomy versus lobectomy for early-stage non-small cell lung cancer.Methods The clinical data of 234 patients with stage ⅠA non-small cell lung cancer and undergoing different surgical methods under video-assisted thoracoscopy admitted to Chongqing Dianjiang General Hospital were retrospectively analyzed,and the patients were divided into the lung segment group and the lung lobe group according to their surgical methods.The clinical characteristics of the patients in the two groups were balanced by a 1-to-1 ratio matching through the propensity score matching method,and each group finally included 63 cases.The perioperative indicators containing operation time,intraoperative blood loss,postoperative thoracic drainage tube indwelling time,thoracic drainage volumes 24 hours and 48 hours after operation and postoperative hospital stay were compared of patients between the two groups.The incidence of postoperative complications such as air leakage>6 days,pulmonary infection,atelectasis,hemoptysis,and hoarseness in the two groups was collected.Results There was no significant difference in the operation time,intraoperative blood loss,thoracic drainage volumes 24 hours and 48 hours after operation,postoperative thoracic drainage tube indwelling time or incidence of postoperative complications of patients between the two groups(P>0.05).The postoperative hospital stay of patients in the lung segment group was shorter than that in the lung lobe group,with statistically significant difference(P=0.003).Conclusion For patients with stage ⅠA non-small cell lung cancer,video-assisted thoracoscopic segmentectomy has similar perioperative efficacy to lobectomy,while segmentectomy has a more significant advantage in shortening the hospital stay.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Based on the focal adhesion kinase(FAK)/steroid receptor coactivator(Src)/extracellular regulated protein kinase(ERK) pathway, this study explored the effects of Xihuang Pills on angiogenesis, invasion, and metastasis in prostate cancer. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to analyze and identify the active ingredients of Xihuang Pills. Bioinformatics techniques, including R language and Perl programs, were employed to analyze the interactions between prostate cancer-related targets and the potential targets of Xihuang Pills. A subcutaneous transplantation tumor model of prostate cancer was established in nude mice using PC3 cells to verify the efficacy and molecular mechanisms of Xihuang Pills. In vitro cellular experiments, including cell proliferation assays(CCK-8), Transwell assays, scratch assays, real-time quantitative reverse transcription PCR, and Western blot, were used to detect the effects of Xihuang Pills on the proliferation, invasion, and migration of prostate cancer cells, as well as on FAK/Src/ERK pathway-related targets. LC-MS/MS identified 99 active ingredients in Xihuang Pills, including gallic acid, gentisic acid, artemisinin, corilagin, phenylbutazone-glucoside, thujic acid, and arecoic acid B. Network pharmacological analysis of the active ingredients in Xihuang Pills revealed that the FAK/Src/ERK signaling pathway was a key pathway in its anti-prostate cancer effects. In vivo and in vitro experiments confirmed that Xihuang Pills significantly inhibited the proliferation, invasion, and migration of PC3 and LNCaP cells, suppressed the growth of PC3 subcutaneous tumors, and reduced the protein expression levels related to the FAK/Src/ERK signaling pathway. In conclusion, the inhibition of angiogenesis, invasion, and metastasis by regulating the FAK/Src/ERK pathway is one of the mechanisms by which Xihuang Pills exert anti-prostate cancer effects.
Humans ; Male ; Prostatic Neoplasms/enzymology* ; Drugs, Chinese Herbal/chemistry* ; Animals ; Mice ; Cell Proliferation/drug effects* ; Mice, Nude ; Cell Movement/drug effects* ; Cell Line, Tumor ; src-Family Kinases/genetics* ; Neovascularization, Pathologic/metabolism* ; Neoplasm Metastasis ; Neoplasm Invasiveness ; Focal Adhesion Kinase 1/genetics* ; Extracellular Signal-Regulated MAP Kinases/genetics* ; MAP Kinase Signaling System/drug effects* ; Focal Adhesion Protein-Tyrosine Kinases/genetics* ; Signal Transduction/drug effects* ; Angiogenesis

Due to various constraints, such as clinical implementation conditions and unique characteristics of acupuncture-moxibustion, some randomized controlled trials (RCTs) of acupuncture-moxibustion still suffer from relatively low quality and limited applicability. The single-arm objective performance criteria/performance goal can be considered as an ideal supplementary and alternative research approach to RCTs. In this paper, the feasibility of applying the single-arm objective performance criteria/performance goal in acupuncture-moxibustion clinical research is explored from the limitations of conducting acupuncture-moxibustion RCTs, the principles, the essential design considerations and key statistical steps. In addition, illustrative examples are provided. The objective is to offer insights into resolving practical difficulties in acupuncture-moxibustion clinical research.
Moxibustion ; Goals ; Acupuncture Therapy ; Acupuncture

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

OBJECTIVE: To investigate the association between short-term exposure to indoor total volatile organic compounds (TVOC) and nocturnal heart rate variability (HRV) among young female adults. METHODS: This panel study recruited 50 young females from one university in Beijing, China from December 2021 to April 2022. All the participants underwent two sequential visits. During each visit, real time indoor TVOC concentration was monitored using an indoor air quality detector. The real time levels of indoor temperature, relative humidity, noise, carbon dioxide and fine particulate matter were monitored using a temperature and humidity meter, a noise meter, a carbon dioxide meter and a particulate counter, respectively. HRV parameters were measured using a 12-lead Holter. Mixed-effects models were used to evaluate the association between the TVOC and HRV parameters and establish the exposure-response relationships, and two-pollutant models were applied to examine the robustness of the results. RESULTS: The mean age of the 50 female subjects was (22.5±2.3) years, and the mean body mass index was (20.4±1.9) kg/m². During this study, the median (interquartile range) of indoor TVOC concentrations was 0.069 (0.046) mg/m³, the median (interquartile range) of indoor temperature, relative humidity, carbon dioxide concentration, noise level and fine particulate matter concentration were 24.3 (2.7) ℃, 38.5% (15.0%), 0.1% (0.1%), 52.7 (5.8) dB(A) and 10.3 (21.5) μg/m³, respectively. Short-term exposure to indoor TVOC was associated with significant changes in time-domain and frequency-domain HRV parameters, and the exposure metric for most HRV parameters with the most significant changes was 1 h-moving average. Along with a 0.01 mg/m³ increment in 1 h-moving average concentration of indoor TVOC, this study observed decreases of 1.89% (95%CI: -2.28%, -1.50%) in standard deviation of all normal to normal intervals (SDNN), 1.92% (95%CI: -2.32%, -1.51%) in standard deviation of average normal to normal intervals (SDANN), 0.64% (95%CI: -1.13%, -0.14%) in percentage of adjacent NN intervals differing by more than 50 ms (pNN50), 3.52% (95%CI: -4.30%, -2.74%) in total power (TP), 5.01% (95%CI: -6.21%, -3.79%) in very low frequency (VLF) power, and 4.36% (95%CI: -5.16%, -3.55%) in low frequency (LF) power. The exposure-response curves showed that indoor TVOC was negatively correlated with SDNN, SDANN, TP, and VLF when the concentration exceeded 0.1 mg/m³. The two-pollutant models indicated that the results were generally robust after controlling indoor noise and fine particulate matter. CONCLUSION Short-term exposure to indoor TVOC was associated with significant negative changes in nocturnal HRV of young women. This study provides an important scientific basis for relevant prevention and control measures.
Humans ; Female ; Adult ; Young Adult ; Air Pollutants/analysis* ; Heart Rate/physiology* ; Volatile Organic Compounds/analysis* ; Carbon Dioxide ; Particulate Matter/adverse effects* ; Environmental Pollutants