1.Machine learning-enabled precision transfusion: research progress, challenges, and prospects
Jiang DENG ; Chaojie WANG ; Ning ZHAO ; Liping LYU ; Ping MA ; Ke ZHANG ; Yanyu ZHANG
Chinese Journal of Blood Transfusion 2026;39(7):967-976
Blood transfusion is an important life-support measure in modern medicine. As clinical demand for transfusion continues to rise, blood supply remains under persistent strain, making the efficient utilization of this precious medical resource a critical component of blood management. Accurate prediction of transfusion needs is of great significance for optimizing blood resource allocation and conserving blood products. Traditional transfusion decision-making relies on clinical experience and simplified scoring systems, which are insufficient to meet the demands of precision medicine. Machine learning (ML) technology can integrate multidimensional data—including demographic characteristics, laboratory indicators, surgical information, and dynamic physiological waveforms—to construct high-performance predictive models, offering a new approach to transfusion prediction. This article systematically reviews the application progress of ML in transfusion prediction across clinical scenarios such as trauma, the perioperative period, and obstetrics. In trauma, ML has been applied to early massive transfusion prediction, prehospital transfusion decision-making, and precise prediction in pediatric trauma. In the perioperative field, applications span specialties including traumatic brain injury, orthopedic surgery, cardiovascular and major vascular surgery, and hepatic surgery. In obstetrics, models can effectively predict postpartum hemorrhage and transfusion requirements associated with cesarean section. Studies have shown that algorithms such as random forest, gradient boosting machines, and deep neural networks achieve area under the receiver operating characteristic curve (AUC) values of 0.83-0.98 in massive transfusion prediction, 0.75-0.97 in perioperative scenarios, and 0.80-0.89 in obstetric transfusion prediction—significantly outperforming traditional scoring tools. However, current studies are generally limited by single-center retrospective designs, insufficient external validation, and inadequate reporting standards; limited model interpretability and challenges in clinical integration further constrain practical translation. Future research should focus on constructing multicenter data cohorts, integrating multimodal data, conducting prospective implementation studies, and deeply embedding models within electronic health record systems, thereby advancing the application of ML to optimize clinical transfusion decision-making.
2.Convergent modulation of default mode network effective connectivity by modified Suanzaoren Decoction and estazolam in patients with chronic insomnia disorder
Ke WANG ; Yiding HAN ; Haohao YAN ; Xingyan GUO ; Wuhong LIN ; Ping YAO ; Min LIU ; Min CHEN ; Longbiao CUI ; Wenbin GUO ; Dongsheng LYU
Sichuan Mental Health 2026;39(4):356-366
BackgroundBoth modified Suanzaoren Decoction and estazolam serve as effective treatments for chronic insomnia disorder (CID). Default mode network (DMN) dysfunction is recognized as the primary pathophysiological mechanism underlying CID. However, it remains unclear whether the two treatments exert their therapeutic effects via convergent modulation of DMN functional connectivity. ObjectiveTo investigate the convergent remodeling characteristics of bidirectional effective connectivity (EC) of core DMN nodes with both the intra-network and the remaining whole-brain regions in CID patients with Yin-deficiency and fire-hyperactivity syndrome following the treatment with modified Suanzaoren Decoction or estazolam, so as to provide neuroimaging evidence for the convergent neural mechanisms underlying the therapeutic effects of both therapies in treating CID. MethodsEighty-two patients diagnosed with CID according to the International Classification of Sleep Disorder, third edition (ICSD-3) were consecutively recruited from the outpatient clinic of the Inner Mongolia Autonomous Region Mental Health Center from October 2020 to September 2023. Based on treatment preference, patients were assigned to receive a 6-week intervention in either the modified Suanzaoren Decoction group (n=52) or the estazolam group (n=30). Ultimately, 66 patients completed follow-up assessments (modified Suanzaoren Decoction group, n=41; estazolam group, n=25). All CID patients underwent resting-state functional magnetic resonance imaging scanning before and after treatment. Core DMN nodes including medial prefrontal cortex (mPFC), bilateral inferior parietal lobule (IPL), and precuneus (PCUN) were selected as seed regions. Granger causality analysis (GCA) was employed to assess bidirectional EC between the seed regions and both the other intra-DMN nodes and the remaining whole-brain regions. Hepatic and renal function indices were detected pre- and post-treatment to evaluate the safety profiles of both treatments. ResultsAt baseline, significant between-group differences were identified in EC from the left IPL to the left middle fronto-orbital gyrus/gyrus rectus (t=5.24, Z=4.84, voxel-level P<0.001, cluster-level P<0.05, GRF-corrected), with the modified Suanzaoren Decoction group exhibiting stronger EC than the estazolam group. No significant between-group differences were observed in EC between other core DMN nodes and remaining whole-brain regions (P>0.05). Within-group pre- to post-treatment comparisons demonstrated consistent connectivity alterations in both groups. Specifically, EC from the left IPL to the supplementary motor area (SMA) decreased after treatment (modified Suanzaoren Decoction group: t=-6.28, Z=5.208; estazolam group: t=-5.58, Z=4.425). Conversely, EC from the SMA to the left IPL increased (modified Suanzaoren Decoction group: t=5.89, Z=4.968; estazolam group: t=6.15, Z=4.720). Furthermore, both groups demonstrated reduced EC from the PCUN to the left IPL (modified Suanzaoren Decoction group: t=-5.85, Z=4.94; estazolam group: t=-5.75, Z=4.515), and elevated EC from the left IPL to the PCUN (modified Suanzaoren Decoction group: t=5.29, Z=4.579; estazolam group: t=4.55, Z=3.826) (voxel-level P<0.001, cluster-level P<0.05, GRF-corrected). No significant pre- to post-treatment differences were observed in hepatic or renal function indices in either group (P>0.05). ConclusionIn CID patients with Yin-deficiency and fire-hyperactivity syndrome, both modified Suanzaoren Decoction and estazolam induce convergent bidirectional remodeling of EC between the left IPL and the SMA and the PCUN. [Funded by Natural Science Fund Project of Inner Mongolia Autonomous Region (number, 2019MS08099); ClinicalTrials.gov number, NCT06452953]
3.Mechanism of sensory neuron TRPV1 desensitization induced by mechanical stimulation to reduce the inflammatory response of synovial fibroblasts in a knee osteoarthritis model
Li ZHANG ; Hua ZHANG ; Ping LI ; Song GAO ; Guangjuan KE ; Liuxin QU
Chinese Journal of Comparative Medicine 2025;35(9):72-81
Objective To construct a model of knee osteoarthritis(KOA)through the co-culture of dorsal root ganglia(DRG)and fibroblast-like synoviocytes(FLSs).To investigate the effects of transient receptor potential vanilloid type 1(TRPV1)desensitization of sensory neurons induced by mechanical stimulation,including the alleviation of the FLSs inflammatory response.Methods DRG neuronal cells were identified through immunofluorescence.The stress loading of DRG neurons was realized using the FX-6000T cell stress system,and the effect of mechanical strain on the activity of DRG neurons was measured using the CCK-8 method.Ca2+ion flux in DRG neurons was studied through flow cytometry.A Transwell chamber and FLSs were used to establish a co-culture system.The contents of the pro-inflammatory factors IL-1β,TNF-α,and TGF-β in the supernatant were determined by ELISA.Gene and protein expression levels of TRPV1 and its desensitizing negative regulatory proteins PP2B,CaM,IL-1β,TNF-α,TGF-β,and α-SMA in DRG neurons were evaluated using RT-qPCR and Western blot,respectively.Results The Ca2+ion flux in DRG neurons increased under inflammatory conditions,and low intensity(sinusoidal,2%,1 Hz,6 h)thumb-pressing-induced mechanical stimulation did not alter Ca2+ion flux(P>0.05).However,middle intensity(sinusoidal,4%,1 Hz,6 h)and high intensity(sinusoidal,8%,1 Hz,6 h)stimulation increased Ca2+ion flux significantly(P<0.05).Notably,high intensity stimulation did not lead to a further increase in Ca2+ion flux over that for middle intensity stimulation(P>0.05).There was no significant effect of low intensity stimulation on TRPV1,PP2B,or CaM gene or protein expression in DRG neurones,on IL-1β,TNF-α,or TGF-βconcentrations in the supernatant of co-cultured cells,or on IL-1β,TNF-α,TGF-β,or α-SMA gene or protein expression in FLSs(P>0.05).Middle and high intensity mechanical stimulation up-regulated TRPV1 at the gene and protein expression levels in DRG neurons in the inflammatory group(P<0.05)but down-regulated PP2B and CaM at the gene and protein expression levels(P<0.05).Middle and high intensity mechanical stimulation decreased IL-1β,TNF-α,and TGF-β levels in the supernatants of co-cultured cells(P<0.05)and decreased the gene and protein expression levels of IL-1β,TNF-α,TGF-β,and α-SMA in FLSs(P<0.05).Conclusions Middle and high intensity thumb-pressing-induced mechanical stimulation induced TRPV1 desensitization of rat sensory neurons,reduced the release of pain mediators,and suppressed the FLSs inflammatory response through downregulating IL-1β,TNF-α,and TGF-β.
4.Medication safety assessment tools for clinical nurses: a scoping review
Shuqi LI ; Ping SHEN ; Juqing KE ; Xiaojuan SHENG ; Ling YUAN ; Yan CHEN ; Qiuju CHEN
Chinese Journal of Modern Nursing 2025;31(35):4862-4868
Objective:To summarize medication safety assessment tools for clinical nurses both domestically and internationally.Methods:Guided by the Joanna Briggs Institute (JBI) scoping review methodology, a systematic search was conducted across CINAHL, Embase, PubMed, Web of Science, SinoMed, China National Knowledge Infrastructure, and WanFang Data. The search period was from the establishment of database to January 1, 2025. Medication safety assessment tools for clinical nurses were extracted, relevant content was systematically analyzed, and the retrieval results were reported in a standardized manner.Results:A total of 28 studies were included, involving 15 medication safety assessment tools for clinical nurses. Assessment methods employed multidimensional and graded self-assessment formats. Based on evaluation perspectives, these tools were categorized into six types, including operational standardization monitoring, cognitive bias calibration, environmental stress testing, capability threshold identification, reporting barrier analysis, and medication information systems. The assessment tools had high reliability and validity, multiple types, and diverse evaluation perspectives.Conclusions:Researchers should carefully select and use assessment tools based on research characteristics. It is necessary to enhance the autonomy of nursing research on medication safety, develop comprehensive and accurate clinical nurse medication safety assessment tools that are adapted to China's clinical context, and promote the improvement of nurse medication safety.
5.Association of eating out of home and type 2 diabetes mellitus in Chinese urban workers: A nationwide study
Fangyan CHEN ; Sitong WAN ; Jinjuan HAO ; Ke SUN ; Annan LIU ; Ling ZHU ; Shuyan WANG ; Jingjing HE ; Ping ZENG
Chronic Diseases and Translational Medicine 2025;11(1):69-77
Background::The prevalence of type 2 diabetes mellitus (T2DM) has been rapidly growing in Chinese populations in recent decades, and the shift in eating habits is a key contributing factor to this increase. Eating out of home (EOH) is one of the major shifts in eating habits during this period. However, the influence of EOH on the incidence of T2DM among Chinese urban workers is unknown.Methods::The cross-sectional study involved an analysis of 13,904 urban workers recruited from 11 health examination centers in the major cities of China to explore the relationship between EOH and T2DM between 2013 September and 2016 March.Results::Average weekly EOH frequency ≥10 times was positively associated with increased incidence of T2DM in the sampled population (OR: 1.31 [1.11-1.54], p < 0.01), most notably in participants ≤45 years old (OR: 1.41[1.11-1.80], p < 0.01]) and in males (OR:1.26 [1.06-1.51], p < 0.01). An EOH frequency of 5 times/week appears as a threshold for a significant increase in the odds of T2DM. Weekly EOH frequency ≥5 times was associated with increased odds of T2DM in a dose-response manner in the total population and almost all subgroups ( poverall association < 0.05 and pnonlinearity ≤ 0.05). Conclusion::This study showed that a frequency of EOH (≥5 times/week) was associated with a frequency-dependent increase in the odds of T2DM urban workers in China. More nutrition promotion is needed to improve the eating behavior of Chinese urban workers to reduce T2DM risk.
6.Surgical treatment and survival analyses of intrahepatic cholangiocarcinoma
Hui ZHANG ; Chenyu JIAO ; Changxian LI ; Feng ZHANG ; Feng CHENG ; Xiaofeng QIAN ; Ke WANG ; Liyong PU ; Chuanyong ZHANG ; Lianbao KONG ; Donghua LI ; Ping WANG ; Aihua YAO ; Xiaofeng WU ; Wei YOU ; Xuehao WANG ; Xiangcheng LI
Chinese Journal of Surgery 2025;63(4):322-330
Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.
7.The impact of myocardial infarct size dynamics on left ventricular remodeling in STEMI patients after primary percutaneous coronary intervention
Si CHEN ; Xin A ; Yiqing ZHAO ; Zhenyan MA ; Ying ZHANG ; Ke LIU ; Lei FU ; Liping ZHANG ; Yongqiang YANG ; Ping LI ; Jinwen TIAN ; Hongbo ZHANG ; Lei ZHAO ; Geng QIAN
Chinese Journal of Cardiology 2025;53(6):653-660
Objective:To explore the impact of changes of myocardial infarct size on left ventricular adverse remodeling in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI).Methods:This was a prospective cohort study. The STEMI patients who underwent primary PCI in the First Medical Center of the Chinese People′s Liberation Army General Hospital, Beijing Anzhen Hospital, Hainan Hospital of the Chinese People′s Liberation Army General Hospital and Guangxi Yulin First People Hospital from January 1, 2017 to January 1, 2022 were enrolled. Cardiac magnetic resonance (CMR) was performed to dynamically assess the myocardial infarct size and calculate the rate of infarct size change between the acute phase (5 to 7 days post-primary PCI) and 6-month follow-up. The endpoint was left ventricular adverse remodeling which was defined as an increase of more than 20% in left ventricular end-diastolic volume (LVEDV) assessed by CMR at 6 months after primary PCI compared with LVEDV at 1 week after primary PCI. Based on serial CMR assessments, the patients were divided into left ventricular adverse remodeling group and non-remodeling group. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of infarct size change for left ventricular adverse remodeling, and according to the optimal cutoff value, improved infarct size was defined as a decrease of >20% in the infarct size measured by CMR at 6 months after primary PCI compared with infarct size at 1 week after primary PCI. Multivariate logistic regression analysis was performed to identify the protective factors and risk factors for left ventricular adverse remodeling.Results:A total of 267 patients were enrolled, aged (58±11) years, with 234 males (87.6%). And 73 cases in the left ventricular remodeling group and 194 cases in the non-remodeling group. Infarct size assessed by CMR at 6 months after primary PCI decreased significantly compared with infarct size at 1 week after primary PCI in the left ventricular remodeling group ((23±13)% vs. (27±12)%, P=0.004), the same as in the non-remodeling group ((18±10)% vs. (23±10)%, P<0.001). The area under the ROC curve for the rate of infarct size change in predicting left ventricular remodeling was 0.735 (95% CI 0.670-0.799, P<0.001), a 20% reduction was the optimal cut-off value. Compared to the patients with non-improved infarct size, the incidence of left ventricular adverse remodeling was significantly lower in the patients with improved infarct size (18% (24/133) vs. 37% (49/134), P=0.001). Multivariate logistic regression analysis showed that improvement in IS was a protective factor for left ventricular adverse remodeling ( OR=0.376, 95% CI 0.236-0.721, P=0.002). Conclusion:Patients with STEMI who experience obvious reduction in infarct size after primary PCI have a significantly reduced risk of left ventricular adverse remodeling.
8.Outcomes of transcatheter transseptal mitral valve-in-valve replacement using Edward's SAPIEN 3 in high surgical risk patients-a multicenter study in China
Xiang CHEN ; Bin WANG ; Yi-wei XU ; Xiao-ping PENG ; Fan QIAO ; Xiang-wen LIANG ; Ke HAN ; Xiao-fei JIANG ; Xiang MA ; Wen-yi YANG ; Guo-sheng FU ; Mao-long SU ; Yan WANG
Chinese Journal of Interventional Cardiology 2025;33(2):79-86
Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0%being females and 70.0%classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0%technical success rate and a 90.0%procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0%)were re-hospitalized due to heart failure,and sadly,one of them(5.0%)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.
9.Isolation,identification,and biological characterization of enterotoxigenic Escherichia coli from a South China tiger
Jing-ru XU ; Zhi-hao ZHU ; Yu-qi LI ; Si-si FAN ; Ya-li KANG ; Yu-bin ZHUO ; Ling-shan HUANG ; Shu-qi QIU ; XUE-YUXI ; Xiao-ping WU ; Yu-ting LIAO ; Wei-ye LIN ; Xiao-ziyi XIAO ; Xue-jin LI ; Teng-teng CHEN ; Xi-pan LIN ; Kai-xiong LIN ; Ke-wei FAN
Chinese Journal of Zoonoses 2025;41(6):567-573
This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.
10.Mechanism of sensory neuron TRPV1 desensitization induced by mechanical stimulation to reduce the inflammatory response of synovial fibroblasts in a knee osteoarthritis model
Li ZHANG ; Hua ZHANG ; Ping LI ; Song GAO ; Guangjuan KE ; Liuxin QU
Chinese Journal of Comparative Medicine 2025;35(9):72-81
Objective To construct a model of knee osteoarthritis(KOA)through the co-culture of dorsal root ganglia(DRG)and fibroblast-like synoviocytes(FLSs).To investigate the effects of transient receptor potential vanilloid type 1(TRPV1)desensitization of sensory neurons induced by mechanical stimulation,including the alleviation of the FLSs inflammatory response.Methods DRG neuronal cells were identified through immunofluorescence.The stress loading of DRG neurons was realized using the FX-6000T cell stress system,and the effect of mechanical strain on the activity of DRG neurons was measured using the CCK-8 method.Ca2+ion flux in DRG neurons was studied through flow cytometry.A Transwell chamber and FLSs were used to establish a co-culture system.The contents of the pro-inflammatory factors IL-1β,TNF-α,and TGF-β in the supernatant were determined by ELISA.Gene and protein expression levels of TRPV1 and its desensitizing negative regulatory proteins PP2B,CaM,IL-1β,TNF-α,TGF-β,and α-SMA in DRG neurons were evaluated using RT-qPCR and Western blot,respectively.Results The Ca2+ion flux in DRG neurons increased under inflammatory conditions,and low intensity(sinusoidal,2%,1 Hz,6 h)thumb-pressing-induced mechanical stimulation did not alter Ca2+ion flux(P>0.05).However,middle intensity(sinusoidal,4%,1 Hz,6 h)and high intensity(sinusoidal,8%,1 Hz,6 h)stimulation increased Ca2+ion flux significantly(P<0.05).Notably,high intensity stimulation did not lead to a further increase in Ca2+ion flux over that for middle intensity stimulation(P>0.05).There was no significant effect of low intensity stimulation on TRPV1,PP2B,or CaM gene or protein expression in DRG neurones,on IL-1β,TNF-α,or TGF-βconcentrations in the supernatant of co-cultured cells,or on IL-1β,TNF-α,TGF-β,or α-SMA gene or protein expression in FLSs(P>0.05).Middle and high intensity mechanical stimulation up-regulated TRPV1 at the gene and protein expression levels in DRG neurons in the inflammatory group(P<0.05)but down-regulated PP2B and CaM at the gene and protein expression levels(P<0.05).Middle and high intensity mechanical stimulation decreased IL-1β,TNF-α,and TGF-β levels in the supernatants of co-cultured cells(P<0.05)and decreased the gene and protein expression levels of IL-1β,TNF-α,TGF-β,and α-SMA in FLSs(P<0.05).Conclusions Middle and high intensity thumb-pressing-induced mechanical stimulation induced TRPV1 desensitization of rat sensory neurons,reduced the release of pain mediators,and suppressed the FLSs inflammatory response through downregulating IL-1β,TNF-α,and TGF-β.

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