OBJECTIVE To explore and predict the quality markers （Q-markers） of Compound xiebai capsules for the treatment of chronic obstructive pulmonary disease （COPD） by constituents analysis combined with network pharmacology and molecular docking studies， and to establish the quality standard of Compound xiebai capsules. METHODS UHPLC-TOF-MS was used for qualitative analysis of Compound xiebai capsules， and the candidate Q-markers of Compound xiebai capsules were screened by combining network pharmacology and molecular docking technology. Further， HPLC was applied to establish the fingerprints of 15 batches of Compound xiebai capsules and to conduct quantitative analysis of the main components. RESULTS A total of 51 components were identified from Compound xiebai capsules. Among them， 15 components， namely oxyberberine， methylworenine， coptisine， tetrahydroberberine， epiberberine， berberine， magnoflorine， gandensin， cucurbitacin D， hydroxygenkwan， jatrorrhizine， columbamine， quercetin， cucurbitacin R， and palmatine， were determined as the candidate Q-markers for Compound xiebai capsules in the treatment of COPD. A total of 13 common peaks were calibrated in the fingerprints of 15 batches of Compound xiebai capsules for COPD treatment， with similarity values ranging from 0.976 to 0.999 compared to the reference fingerprint. Seven components were identified among these peaks， namely peak 5 （magnoflorine）， peak 8 （jatrorrhizine）， peak 9 （epiberberine）， peak 10 （columbamine）， peak 11 （coptisine）， peak 12 （palmatine）， and peak 13 （berberine）. Their respective contents were （0.267±0.048）， （0.453±0.084）， （0.572±0.160）， （0.392±0.074）， （1.076±0.273）， （1.477±0.271）， and （6.664±1.249） mg/g （ n ＝3）. CONCLUSIONS This study predicted 15 candidate Q-markers of Compound xiebai capsules in the treatment of COPD and established the fingerprint along with a quantitative determination method for seven major components.

OBJECTIVE: To propose a machine learning-based method for predicting the trajectories during manual acupuncture manipulation (MAM), aiming to improve the precision and consistency of acupuncture practitioner' operation and provide the real-time suggestions on MAM error correction. METHODS: Computer vision technology was used to analyze the hand micromotion when holding needle during acupuncture, and provide a three-dimensional coordinate description method of the index finger joints of the holding hand. Focusing on the 4 typical motions of MAM, a machine learning-based MAM trajectory predictive model was designed. By integrating the changes of phalangeal joint angle and hand skeletal information of acupuncture practitioner, the motion trajectory of the index finger joint was predicted accurately. Besides, the roles of machine learning-based MAM trajectory predictive model in the skill transmission of acupuncture manipulation were verified by stratified randomized controlled trial. RESULTS: The performance of MAM trajectory predictive model, based on the long short-term memory network (LSTM), obtained the highest stability and precision, up to 98%. The learning effect was improved when the model applied to the skill transmission of acupuncture manipulation. CONCLUSION The machine learning-based MAM predictive model provides acupuncture practitioner with precise action prediction and feedback. It is valuable and significant for the inheritance and error correction of manual operation of acupuncture.
Humans ; Acupuncture Therapy/instrumentation* ; Machine Learning ; Adult ; Male ; Female

OBJECTIVE: To investigate the effect of manual acupuncture manipulations (MAMs) on subcutaneous muscle tissue, by developing quantitative models of "lifting and thrusting" and "twisting and rotating", based on machine learning techniques. METHODS: A depth camera was used to capture the acupuncture operator's hand movements during "lifting and thrusting" and "twisting and rotating" of needle. Simultaneously, the ultrasound imaging was employed to record the muscle tissue responses of the participants. Amplitude and angular features were extracted from the movement data of operators, and muscle fascicle slope features were derived from the data of ultrasound images. The dynamic time warping barycenter averaging algorithm was adopted to align the dual-source data. Various machine learning techniques were applied to build quantitative models, and the performance of each model was compared. The most optimal model was further analyzed for its interpretability. RESULTS: Among the quantitative models built for the two types of MAMs, the random forest model demonstrated the best performance. For the quantitative model of the "lifting and thrusting" technique, the coefficient of determination (R²) was 0.825. For the "twisting and rotating" technique, R² reached 0.872. CONCLUSION Machine learning can be used to effectively develop the models and quantify the effects of MAMs on subcutaneous muscle tissue. It provides a new perspective to understand the mechanism of acupuncture therapy and lays a foundation for optimizing acupuncture technology and designing personalized treatment regimen in the future.
Humans ; Acupuncture Therapy/methods* ; Machine Learning ; Male ; Adult ; Female ; Subcutaneous Tissue/diagnostic imaging* ; Young Adult

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

The study aims to investigate the impacts of prolyl oligopeptidase (POP) on the replication of foot-and-mouth disease virus (FMDV) in BHK-21 cells. Firstly, the effects of FMDV replication on POP expression in BHK-21 cells were analyzed by Western blotting and Real-time reverse transcription polymerase chain reaction (RT-qPCR). Secondly, a eukaryotic expression plasmid for POP was constructed, and the effects of POP overexpression on the replication of two different serotypes of FMDV were assessed by Western blotting, RT-qPCR, and virus titer assays. Thirdly, specific small interfering RNAs (siRNAs) targeting POP were synthesized, and their efficiency in interfering with endogenous POP expression was identified by RT-qPCR. The impacts of downregulating endogenous POP expression on FMDV replication were further evaluated by Western blotting, RT-qPCR, and virus titer assays. The results indicated that FMDV infection did not significantly affect POP expression in BHK-21 cells. Overexpression of POP dose-dependently enhanced the replication of both FMDV/O and FMDV/A serotypes. Conversely, siRNA-mediated downregulation of endogenous POP expression markedly suppressed FMDV/O replication. This study is the first to demonstrated that the role of the host POP protein in promoting FMDV replication in BHK-21 cells, thereby providing a critical theoretical foundation and potential molecular targets for developing efficient candidate cell strains for foot-and-mouth disease inactivated vaccines.
Foot-and-Mouth Disease Virus/genetics* ; Virus Replication/genetics* ; Prolyl Oligopeptidases ; Serine Endopeptidases/physiology* ; Animals ; Cell Line ; RNA, Small Interfering/genetics* ; Foot-and-Mouth Disease/virology* ; Cricetinae

Objective: To observe the effect of Xipayimaizibizi oral liquid (XP) in an overactive bladder (OAB) experimental rat model and to explore its pharmacological mechanisms. Methods: Network pharmacology was used to explore the potential mechanisms of action of XP. The rats underwent bladder outlet obstruction surgery and were administered the corresponding drug concentrations by gavage for 4 weeks. The study observed the body weight, water intake, bladder and kidney indices (to evaluate their general status), urination behavior pattern (to observe frequency and urgency), and urodynamics (to measure bladder parameters). Hematoxylin and eosin and Masson's trichome staining were used to observe changes in the bladder structure. Enzyme-linked immunosorbent assay was used to measure the levels of nerve growth factor, brain-derived neurotrophic factor, and acetylcholine in the urine. The key targets involved in these mechanisms were validated using reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, and western blot in vivo/vitro experiments. Result: Network pharmacological analysis predicted that XP may alleviate OAB by affecting the cholinergic synapse and calcium signaling pathways. XP treatment significantly reduced the bladder index, improved urine behavior and urodynamic parameters, decreased the neurotransmitters in urine, and reduced the thickness of the bladder wall and collagen ratio. These results indicate that XP can alleviate OAB symptoms and improve the bladder structure. In vivo/vitro experiments further demonstrated that XP can inhibit targets, such as muscarinic acetylcholine receptor 2, and participate in cholinergic synapses to further regulate the parasympathetic nervous system. It can also reduce the overexpression of Ca2+ caused by agonists, inhibit targets such as transient receptor potential vanilloid type 1, and participate in calcium signaling pathways to maintain Ca2+ homeostasis. Conclusion These results suggest that XP inhibited bladder overactivity by maintaining Ca2+ homeostasis and regulating the parasympathetic nervous system.

In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.

Background: Hypertension is a major risk factor for cardiovascular diseases, including AF, which is one of the most common cardiac arrhythmias globally. AF is strongly associated with an increased risk of stroke, heart failure (HF), and cardiovascular mortality. Although intensive blood pressure lowering has been shown to reduce adverse cardiovascular events, its effect on the risk of AF remains debated. Some studies suggest a beneficial effect, whereas others are inconclusive. Therefore, a comprehensive review and meta-analysis are needed to clarify these effects. Objective: This study aims to evaluate the impact of intensive blood pressure lowering on the incidence of atrial fibrillation (AF) in hypertensive patients. Methods: We performed a systematic review and meta-analysis by searching PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library up to September 2, 2024, for randomized controlled trials comparing intensive blood pressure lowering with standard treatment in hypertensive patients. Studies were included if participants were 40 year or older with systolic blood pressure between 130 and 180 mm Hg (1 mm Hg≈0.133 kPa). Data extraction was conducted by 2 independent researchers, and statistical analysis was performed using Review Manager (RevMan) 5.4. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. A random-effects model was applied if heterogeneity was detected (I > 50%). Results: A total of 6 randomized controlled trials involving 34,824 participants were included in the analysis. Intensive blood pressure lowering significantly reduced the risk of new-onset AF compared with standard treatment (RR = 0.76, 95% CI = 0.62-0.93, p < 0.01, I = 0%). Reductions were also observed in stroke (RR = 0.71, 95% CI = 0.58-0.87, p < 0.005, I = 7%), HF (RR = 0.67, 95% CI = 0.45-0.99, p = 0.05, I = 53%), and nonfatal coronary events (RR = 0.80, 95% CI = 0.70-0.92, p < 0.005, I = 39%). However, intensive blood pressure lowering had no significant effect on cardiovascular mortality or all-cause mortality compared with standard treatment. Discussion: Intensive blood pressure lowering significantly reduces the risk of AF and other cardiovascular events, such as stroke, HF, and nonfatal coronary events, particularly among high-risk hypertensive patients. These findings support the potential benefits of intensive blood pressure management in reducing AF incidence and improving overall cardiovascular outcomes, but the evidence is limited.

Objective To investigate the impact of body mass index(BMI)on the perioperative outcomes and prognosis in patients with clear cell renal cell carcinoma(ccRCC)undergoing robot-assisted partial nephrectomy(RAPN),so as to provide reference for optimizing clinical management strategies.Methods The clinical data of 745 ccRCC patients undergoing RAPN at our hospital during 2014 and 2023 were retrospectively analyzed.Patients were categorized into three groups according to preoperative BMI:normal weight(18＜BMI＜24,n=202),overweight(24＜BMI＜28,n=428),and obese(BMI≥28,n=115).Baseline characteristics,surgical parameters,postoperative complications,pre-and post-operative estimated glomerular filtration rate(eGFR),and overall survival(OS)were compared among the groups.Multivariate regression analyses were performed to adjust potential confounders.Results Among baseline characteristics,only the gender distribution differed significantly among the three groups(P=0.009).Multivariate analysis showed that gender had no significant effects on reoperation,transfusion,operation time,intraoperative blood loss,or postoperative renal function.The median follow-up was 32(12,55)months.Compared with the normal-weight group,the obese group had longer operation time[140.0(115.0,170.0)min vs.160.0(125.0,190.0)min,P=0.009]and greater intraoperative blood loss[50.0(50.0,100.0)mL vs.100.0(50.0,150.0)mL,P=0.003].No statistically significant differences were observed among the three groups in pre-and post-operative eGFR,overall complication rate,long-term follow-up eGFR,or OS(P＞0.05).Conclusion RAPN provides comparable surgical benefits across BMI categories in patients with ccRCC;however,obese patients may experience increased operation time and blood loss.

Objective To investigate the infection status and clinical parameters of human metapneumovirus(HMPV)in children with acute respiratory tract infections in Jianyang area.Methods A total of 2 669 hospitalized children with acute respiratory tract infec-tions at Jianyang People's Hospital from March 2023 to February 2024 were enrolled.Thirteen kinds of respiratory pathogens were de-tected using multiplex PCR and capillary electrophoresis.The clinical data of HMPV-infected children were collected and analyzed.Re-sults Out of 2 669 children with acute respiratory tract infections,209 were detected with HMPV,with a positive rate of 7.83%.HMPV-positive children were mainly concentrated in under 5 years old(73.21%),with cough,fever,wheezing,and shortness of breath as main clinical manifestations.The rate of single HMPV infection was 58.85%,and those of mixed bacterial infection and mixed viral infection were 26.69% and 13.88%,respectively.The levels of white blood cells(WBC),lymphocytes(LYM),platelets(PLT),C-reactive protein(CRP),alanine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH),troponin I(cTn I),and procalcitonin(PCT)in the mixed infection group were significantly higher than those in the single HMPV infection group(P＜0.05),while the levels of hemoglobin(Hb),total protein(TP),and creatinine(Cr)were significantly lower than those in the single HMPV infection group(P＜0.05).Compared with the non-severe pneumonia group,the levels of WBC,Hb,PLT,and CRP in the severe pneumonia group were significantly increased(P＜0.05).Multivariate Logistic regression analysis showed that age＜3 years,co-infection,and CRP≥20 mg/L were risk factors for severe HMPV pneumonia(P＜0.05).Conclusion HMPV is one of the important pathogens causing acute respiratory tract infections in children in Jianyang area.The elevated levels of some laboratory indicators are associated with the severity of infection.Early and comprehensive bacteriological testing and detection of inflammatory markers are beneficial for guiding clinical treatment.