Objective: To investigate the effect of the senescence state of parental human bone marrow mesenchymal stem cells (BMSCs) on the osteoinductive properties of their derived apoptotic vesicles (apoVs), and to provide an experimental basis and a quality control reference for the treatment of alveolar bone defects and osteoporosis based on apoVs. Methods: A replicative senescence model of human aging BMSCs (A-BMSCs) was established via serial passaging, with young BMSCs (Y-BMSCs) serving as controls. Following the induction of apoptosis with staurosporine, apoVs were isolated from Y-BMSCs and A-BMSCs (termed Y-apoVs and A-apoVs, respectively) via differential centrifugation. The physicochemical properties (morphology, size, zeta potential, and yield) and protein markers of both apoV populations were systematically characterized. Subsequently, Y-BMSCs were divided into a proliferation medium (PM) group, osteogenic induction medium (OM) group, OM + Y-apoVs group, and OM + A-apoVs group. The osteoinductive efficacy in vitro was evaluated by alkaline phosphatase (ALP) staining, alizarin red S staining, and quantitative real-time PCR detection of key osteogenic genes, including runt-related transcription factor 2 (RUNX2), ALP, osteopontin (OPN), and osterix (OSX). Approved by the Institutional Animal Care and Use Committee, in vivo biodistribution (labelling apoVs with the red fluorescent dye PKH26) and bone regeneration efficacy were assessed in 18-month-old osteoporotic C57BL/6 mice. Mice were randomly divided into a control group (injected with phosphate-buffered saline), Y-apoVs group (injected with Y-apoVs), and A-apoVs group (injected with A-apoVs). Following tail-vein injection administration of apoVs for 8 weeks, bone regeneration was evaluated via micro-computed tomography and histological analysis. Results: Electron microscopy and particle size analysis revealed that both Y-apoVs and A-apoVs displayed typical biconcave discoid structures, with diameters mainly ranging from 100 to 500 nm. Western blot assays confirmed high expression of universal vesicle markers (CD9, CD63, CD81) and the apoptotic marker Fas in both groups. Y-apoVs and A-apoVs exhibited indistinguishable morphologies, size distributions, zeta potentials, and yields. In vitro experiments showed that, compared with the PM group, the OM, OM + A-apoVs, and OM + Y-apoVs groups significantly enhanced ALP activity, calcium nodule formation, and the expression of osteogenic genes (RUNX2, ALP, OPN, OSX) in recipient Y-BMSCs (P<0.05); moreover, compared with the OM and OM + A-apoVs groups, the OM + Y-apoVs group exhibited a more significant promoting effect (P<0.05). An in vivo analysis demonstrated that tail-vein-injected apoVs effectively homed to bone tissue. Moreover, the Y-apoVs group significantly improved trabecular microarchitecture, bone mineral density, and bone volume fraction in aged mice, exhibiting superior therapeutic efficacy over the control and A-apoVs groups (P<0.05) Conclusion The senescence state of parental cells significantly impairs the osteoinductive ability of BMSC-derived apoVs. Y-apoVs are effective biological agents for the treatment of age-related bone loss.

Objective To investigate the distribution characteristics of Oncomelania hupensis snails in Yunnan Province fol-lowing interruption of schistosomiasis transmission, so as to provide the evidence for assessing the risk of schistosomiasis transmission and scientifically formulating the schistosomiasis surveillance program. Methods According to the requirements of the National Schistosomiasis Surveillance Scheme (2020 Edition), O. hupensis snail surveillance data were collected from 18 schistosomiasis-endemic counties (cities, districts) in Yunnan Province from 2020 to 2024, including area of snail survey, area of snail habitats, area of re-emerging snail habitats, number of frames surveyed, number of frames with O. hupensis snails, number of O. hupensis snails captured, and number of living snails, and the occurrence of frames with snails and mean density of living snails were calculated. Changes in snail status over the 5-year period from 2020 to 2024 and the differences in snail distributions specified by epidemic intensity, environmental type, and vegetation type were analyzed. Results The areas of snail survey increased from 1 727.96 hm² in 2020 to 3 894.45 hm² in 2024 (peak) across 18 schistosomiasis-endemic counties (cities, districts) in Yunnan Province during the period from 2020 through 2024. The areas of snail habitats increased from 70.36 hm² in 2020 to a peak in 2023 (172.04 hm²), followed by a reduction to 132.36 hm² in 2024, and the areas of re-emerging snail habitats increased from 42.71 hm² in 2020 to a peak in 2022 (78.43 hm²), followed by a reduction to 40.21 hm² in 2024. The occurrence of frames with snails and mean density of living snails increased from 1.24% (3 025/244 404) and (0.033 2 ± 0.038 7) snails/0.1 m² in 2020 to peaks at 2.03% (6 231/307 563) and (0.066 9 ± 0.068 4) snails/0.1 m² in 2023, followed by reductions to 1.04% (5 829/559 941) and (0.032 6 ± 0.057 7) snails/0.1 m² in 2024, respectively. There was a significant difference in the occurrence of frames with snails over the 5-year study period (χ² = 1 962.95, P < 0.05), and the occurrence of frames with snails reduced by 48.71% in 2024 relative to in 2023 (χ² = 1 411.05, P < 0.005); however, there was no significant difference in the mean density of living snails over the 5 years (H = 5.310, P > 0.05). There were significant differences in the occurrence of frames with snails (χ² = 481.27, P < 0.05) and mean density of living snails (H = 6.872, P < 0.05) in schistosomiasis-endemic areas with different epidemic intensities. The occurrence of frames with snails (χ² = 25.32 and 38.70, both P values < 0.017) and mean density of living snails (Z = 28.55 and 49.96, both P values < 0.017) were higher in schistosomiasis transmission-interrupted and eliminated areas with snails than in schistosomiasis-eliminated areas without snails, and the occurrence of frames with snails (χ² = 453.54, P < 0.017) and mean density of living snails (Z = −56.97, P < 0.017) were higher in schistosomiasis-eliminated areas with snails than in schistosomiasis transmission-interrupted areas with snails. O. hupensis snails were mainly distributed in paddy fields, dry farmlands and ditches; however, the occurrence of frames with snails (13.40%, 424/3 164) and mean density of living snails [(0.252 8 ± 0.158 7) snails/0.1 m²] were higher in ponds/weirs than in other types of environments (both P values < 0.05). Rice, dry farmland crops and weeds were main vegetations in which O. hupensis snails were distributed, and the occurrence of frames with snails (2.29%, 7 111/310 140) and mean density of living snails [(0.072 3 ± 0.018 9) snails/0.1 m²] were higher in weeds than in other types of environments (both P values < 0.05). Conclusions O. hupensis snails have been effectively controlled in Yunnan Province following implementation of integrated schistosomiasis control measures; however, there are still risk factors for schistosomiasis transmission, including reduced attention to schistosomiasis control and snail re-emergence. Improved control efforts and surveillance system construction and timely identification of risk factors of snail status and timely management are recommended to ensure the achievement of the target of schistosomiasis elimination as scheduled.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective To analyze the causes and compensation characteristics of medical damage disputes in Anhui Province in recent years,and provide reference suggestions for effectively controlling and reducing the incidence of medical errors and doctor-patient conflicts.Methods The 1 876 cases of medical damage disputes in Anhui Province from 2017 to 2022 were included in the judgment documents network,and their occurrence years and causes of disputes were analyzed.Results The number of medical malpractice cases did not decrease significantly,and the average amount of compensation continued to increase;the top three causes of disputes were improper treatment or surgery(54.6%),and the average first place of actual compensation was improper medication or adverse drug reactions,and in terms of hospital level,1 009 cases(53.8%)were concentrated in tertiary public hospitals,the average actual compensation amount of private hospitals ranked first;the top three departments were surgery(44.62%);the highest incidence of damage was death(40.2%),and the average compensation amount for first-class disability was the highest.Hospitals were mainly responsible for secondary responsibilities(38.7%).Conclusion The contradiction between doctors and patients is still serious,so it is necessary to promote the construction of tight medical association and medical community,guide the allocation of medical resources,pay attention to risk sharing and management optimization,and reduce the incidence of medical damage disputes.

Objective:To investigate the risk factors associated with preoperative heart failure in elderly patients with intertrochanteric fracture and evaluate their predictive efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 163 elderly patients with intertrochanteric fracture admitted to the Affiliated Drum Tower Hospital of Nanjing University School of Medicine from July 2018 to July 2022, including 57 males and 106 females, aged 63-98 years [83.3(78.0, 87.0)years]. The patients were divided into high-risk heart failure group ( n=66) and non-high-risk group ( n=97) based on whether the serum B-type natriuretic peptide (BNP) level within 24 hours on admission was greater than 100 pg/ml. The following data in the two groups were collected, including gender, age, AO/OTA fracture classification, fracture laterality, associated underlying comorbidities (diabetes, cardiovascular diseases, cerebral infarction), past history of fracture, history of surgeries, time from injury to hospitalization less than 48 hours, first blood pressure on admission, first routine blood test on admission [leukocyte count (WBC), neutrophil count (NEUT), lymphocyte count, platelet (PLT), hemoglobin (Hb)], first blood biochemistry on admission [alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), albumin, glucose, serum calcium, creatinine, glomerular filtration rate (GFR), and first other related tests on admission [D-dimer, prothrombin time (PT), C-reactive protein (CRP)]. Independent risk factors for preoperative heart failure in elderly patients with intertrochanteric fracture were identified through univariate analysis and binary logistic regression analysis. The predictive efficacy of each indicator or two combined indicators for preoperative heart failure in elderly patients with intertrochanteric fractures was assessed by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results:Univariate analysis demonstrated that age, associated cardiovascular diseases, history of fracture, time from injury to hospitalization less than 48 hours, Hb, creatinine and GFR were significantly correlated with the preoperative heart failure ( P<0.05), while gender, AO/OTA fracture classification, fracture laterality, diabetes, cerebral infarction, history of surgeries, blood pressure, WBC, NEUT, lymphocyte count, PLT, CRP, ALT, AST, LDH, albumin, glucose, serum calcium, D-dimer, PT, and CRP were not correlated with the preoperative heart failure in elderly patients with intertrochanteric fractures ( P>0.05). Logistic regression analysis revealed that age (95% CI 1.02, 1.15, P<0.05), associated cardiovascular disease (95% CI 1.31, 5.88, P<0.01), Hb (95% CI 0.96, 1.00, P<0.05), and GFR (95% CI 0.97, 1.00, P<0.05) were independent risk factors for heart failure in elderly patients with intertrochanteric fracture. ROC curve analysis demonstrated that age, associated cardiovascular diseases, Hb, and GFR could predict preoperative heart failure in elderly patients with intertrochanteric fractures, with the combination of associated cardiovascular disease and GFR showing a relatively higher predictive ability (AUC=0.76, 95% CI 0.68, 0.84). Conclusions:Age, associated cardiovascular diseases, Hb and GFR are independent risk factors for preoperative heart failure in elderly patients with intertrochanteric fracture. Moreover, the combination of associated cardiovascular diseases and GFR possesses a relatively higher predictive value for preoperative heart failure in elderly patients with intertrochanteric fracture.

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

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.

To develop a novel immunocastration vaccine for animals,researchers designed and syn-thesized the recombinant plasmid pET-30a-SF which could express the recombinant protein SF.This protein was then conjugated in vitro with the synthetic peptide STGP to prepare the SF-STGP nanoparticle vaccine,and its immunocastration effect on mice was studied.The Spy Catcher and ferritin amino acid sequences were connected via GGGGS,and after codon optimization for E.coli,the recombinant plasmid pET-30a-SF was constructed and transformed into E.coli for in-duced expression.The recombinant protein SF was purified using Ni-column affinity chromatogra-phy and characterized.The peptide STGP,composed of Spy Tag,GnRH,and PADRE connected by GGGS,was conjugated with the recombinant protein SF in vitro.The self-assembled nanoparticles were observed using transmission electron microscopy(TEM)and dynamic light scattering(DLS).The prepared SF-STGP nanoparticles were mixed with MONTANIDE ISA 206 VG at a 1∶1 ratio to form the vaccine,which was then subcutaneously injected into male BALB/c mice for immunocastration evaluation.The recombinant protein SF showed the highest soluble expression when induced at 18 ℃ with 0.25 mmol/L IPTG for 14 h,and the maximum conjugation efficiency with STGP was achieved at a 1∶8 molar ratio.TEM and DLS analyses revealed that both the re-combinant protein SF and SF-STGP could self-assemble into nanoparticles with average diameters of 16.2 nm and 17.8 nm,respectively.Mouse immunization results demonstrated that the SF-STGP nanoparticle vaccine generated specific GnRH antibodies after the first immunization,with the spe-cific antibody D45o reaching its peak at the 10 th week.The SF-STGP+ISA 206 immunization group showed a peak D450 value of 2.8,and the specific antibody levels in all immunization groups were significantly higher than those in the control group(P＜0.05).Additionally,the SF-STGP nanoparticle vaccine effectively reduced serum testosterone levels in mice,with the testosterone concentration in the immunization groups being significantly lower than that in the control group(P＜0.05).Compared to the control group,the immunization group exhibits testicular atrophy.The constructed SF-STGP nanoparticle vaccine proves to be a highly effective immunogen,capable of inducing testicular atrophy and reducing gonadal hormone concentrations,demonstrating excellent castration effects.This study provides new insights into immunocastration vaccines for mammals.

Objective:To evaluate the efficacy of modified splenic arteriovenous shunt surgery at the distal pancreatic tail in combined pancreas-kidney transplantation.Methods:A retrospective analysis was conducted on 24 recipients who underwent combined pancreas-kidney transplantation with the modified splenic arteriovenous shunt at the pancreatic tail from November 2023 to October 2024 (shunt group) and 231 recipients who received conventional splenic artery and vein ligation since 2016 (ligation group). The incidence of perioperative thrombosis and severe adverse events was compared between the two groups using the chi-square test or Fisher's exact test. Independent sample t-tests were performed to assess postoperative pancreatic and renal function recovery as well as blood perfusion in 15 recipients from the shunt group and 20 from the ligation group who underwent CT perfusion imaging (CTP).Results:The incidence of perioperative splenic arteriovenous thrombosis was lower in the shunt group (0) compared to the ligation group (4.76%, 11/231), though the difference was not statistically significant ( P=0.606). One month postoperatively, the shunt group demonstrated significantly lower serum amylase levels than the ligation group (99.61±19.62 vs. 148.20±70.67 U/L, P=0.018). However, at the time of CTP examination, serum lipase (67.87±32.35 vs. 45.11±17.94 U/L, P=0.014) and creatinine levels (131.79±26.41 vs. 112.1±24.98 μmol/L, P=0.034) were significantly higher in the shunt group. Urea nitrogen levels were also significantly higher in the shunt group both one month postoperatively (11.24±4.64 vs. 8.51±3.01 mmol/L, P=0.043) and at the CTP examination (10.41±1.78 vs. 6.87±1.91 mmol/L, P=0.001). Regarding pancreatic perfusion, blood volume in both the pancreatic head (15.99 ± 3.51 vs. 20.67 ± 5.47 ml/100 g, P = 0.024) and tail (17.19±4.24 vs. 27.40±19.80 ml/100 g, P=0.039) was significantly lower in the shunt group. After one minute of splenic artery perfusion, the shunt group exhibited significantly higher splenic artery blood flow (755.85±101.50 vs. 574.00 ± 142.06 ml·min -1· (100 g) -1, P<0.001) and blood volume (58.90 ±19.93 vs. 23.21±17.02 ml/100 g, P=0.007) compared to the ligation group. These differences persisted after two minutes of perfusion (blood flow: 793.83±68.57 vs. 503.78 ± 130.80 ml·min -1· (100 g) -1, P<0.001; blood volume: 64.22±15.74 vs. 34.32±20.39 ml/100 g, P=0.002). For the transplanted kidney, the shunt group had significantly lower blood flow (113.10±28.55 vs. 232.76±113.37 ml·min -1· (100 g) -1, P<0.001), blood volume (28.95±10.79 vs. 38.36±12.38 ml/100 g, P=0.047), and capillary surface permeability (PS) (26.49±16.57 vs. 43.02±20.37, P = 0.042) in the upper pole. Similar reductions in blood flow, blood volume, and PS were observed in the middle dorsal region ( P=0.018, 0.021, and 0.048, respectively) and lower pole ( P<0.001, P=0.048, and P=0.012, respectively). Conclusion:The modified splenic arteriovenous shunt at the pancreatic tail appears to be a safe and effective approach to reducing the risk of pancreatic graft thrombosis. This technique facilitates effective diversion of pancreatic parenchymal blood flow into the splenic vein, alleviating hyperperfusion of the transplanted pancreas. While renal blood perfusion was reduced postoperatively, it did not adversely affect renal function.