ObjectiveTo investigate the mechanism by which Feixin decoction treats hypoxic pulmonary hypertension （HPH） by regulating the peroxisome proliferator-activated receptor gamma （PPARγ）/nuclear factor-kappa B （NF-κB）/NOD-like receptor pyrin domain containing 3 （NLRP3） signaling pathway. MethodsForty-eight male SD rats were randomly allocated into normal， hypoxia， and low-， medium- and high-dose （5.85， 11.7， 23.4 g·kg^-1， respectively） Feixin decoction groups， with 8 rats in each group. Except the normal group， the remaining five groups were placed in a hypoxia chamber with an oxygen concentration of （10.0±0.5）% for 8 h per day， 28 days， and administrated with corresponding drugs during the modeling process. After 4 weeks of treatment， echocardiographic parameters ［pulmonary artery acceleration time （PAT）， pulmonary artery ejection time （PET）， right ventricular anterior wall thickness （RVAWd）， and tricuspid annular plane systolic excursion （TAPSE）］ were measured for each group. The right ventricular systolic pressure （RVSP） was measured by the right heart catheterization method， and the right ventricular hypertrophy index （RVHI） was calculated by weighing the heart. The pathological changes in pulmonary arterioles were observed by hematoxylin-eosin staining. The co-localization of α-smooth muscle actin （α-SMA） with NLRP3， N-terminal gasdermin D （N-GSDMD）， and cysteinyl aspartate-specific proteinase-1 （Caspase-1） in pulmonary arteries was detected by immunofluorescence. The protein levels of PPARγ， NF-κB， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， N-GSDMD， interleukin-1β （IL-1β）， interleukin-18（IL-18）， and cleaved Caspase-1 in the lung tissue was determined by Western blot. The ultrastructural changes in pulmonary artery smooth muscle cells （PASMCs） were observed by transmission electron microscopy. ResultsCompared with the normal group， the hypoxia group showed increased RVSP and RVHI （P<0.01）， decreased right heart function （P<0.01）， increased pulmonary vascular remodeling （P<0.01）， increased co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 in pulmonary arterioles （P<0.01）， up-regulated protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， a down-regulated protein level of PPARγ （P<0.05， P<0.01）， and pyroptosis in PASMCs. Compared with the hypoxia group， Feixin decoction reduced RVSP and RVHI， improved the right heart function and ameliorated pulmonary vascular remodeling （P<0.05， P<0.01）， decreased the co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， up-regulated the protein level of PPARγ （P<0.05， P<0.01）， and alleviated pyroptosis in PASMCs. ConclusionFeixin decoction can ameliorate pulmonary vascular remodeling and right heart dysfunction in chronically induced HPH rats by regulating pyroptosis in PASMCs through the PPARγ/NF-κB/NLRP3 pathway.

Objective To assess the efficacy of pirfenidone combined with PD-L1 inhibitor for treatment of bladder cancer in a mouse model and its effect on tumor immune microenvironment modulation.Methods Forty C57BL/6 mouse models bearing ectopic human bladder cancer xenografts were randomized into control group,PD-L1 inhibitor group,pirfenidone group and combined treatment group(n=10).After successful modeling,PD-L1 inhibitor treatment was administered via intraperitoneal injection at 12.5 mg/kg every 3 days,and oral pirfenidone(500 mg/kg)was given on a daily basis.The survival rate of the mice and tumor growth rate were compared among the 4 groups.The expressions of CD3,CD8,CD45,E-cadherin and N-cadherin in the tumor tissues were detected with immunohistochemistry after the 21-day treatment,and bone marrow-derived suppressor cells(MDSCs)were observed with immunofluorescence staining;serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),urea nitrogen(BUN),creatinine(CRE)and lactate dehydrogenase(LDH-L)were analyzed using an automated biochemical analyzer.Results Treatment with PD-L1 inhibitor and pirfenidone alone both significantly decreased tumor growth rate and tumor volume at 21 days(P<0.05),but the combined treatment produced an obviously stronger inhibitory effect(P<0.05).PD-L1 inhibitor and pirfenidone alone significantly increased E-cadherin expression and decreased N-cadherin expression in the tumor tissue(P<0.05).The two treatments both significantly increased the percentage of CD3+,CD8 and CD45+ T cells and decreased the percentage of Ly-6G+CD11b+MDSCs in the tumor tissue,and these changes were more obvious in the combined treatment group(P<0.05).No significant differences were found in serum ALT,AST,BUN,CRE or LDH-L levels among the 4 groups(P>0.05).Conclusion Combined treatment with pirfenidone and PD-L1 inhibitor significantly inhibits the progression of bladder cancer in mice possibly by regulating tumor immune microenvironment and inhibiting epithelial-mesenchymal transition of the tumor cells.

Objective To assess the efficacy of pirfenidone combined with PD-L1 inhibitor for treatment of bladder cancer in a mouse model and its effect on tumor immune microenvironment modulation.Methods Forty C57BL/6 mouse models bearing ectopic human bladder cancer xenografts were randomized into control group,PD-L1 inhibitor group,pirfenidone group and combined treatment group(n=10).After successful modeling,PD-L1 inhibitor treatment was administered via intraperitoneal injection at 12.5 mg/kg every 3 days,and oral pirfenidone(500 mg/kg)was given on a daily basis.The survival rate of the mice and tumor growth rate were compared among the 4 groups.The expressions of CD3,CD8,CD45,E-cadherin and N-cadherin in the tumor tissues were detected with immunohistochemistry after the 21-day treatment,and bone marrow-derived suppressor cells(MDSCs)were observed with immunofluorescence staining;serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),urea nitrogen(BUN),creatinine(CRE)and lactate dehydrogenase(LDH-L)were analyzed using an automated biochemical analyzer.Results Treatment with PD-L1 inhibitor and pirfenidone alone both significantly decreased tumor growth rate and tumor volume at 21 days(P<0.05),but the combined treatment produced an obviously stronger inhibitory effect(P<0.05).PD-L1 inhibitor and pirfenidone alone significantly increased E-cadherin expression and decreased N-cadherin expression in the tumor tissue(P<0.05).The two treatments both significantly increased the percentage of CD3+,CD8 and CD45+ T cells and decreased the percentage of Ly-6G+CD11b+MDSCs in the tumor tissue,and these changes were more obvious in the combined treatment group(P<0.05).No significant differences were found in serum ALT,AST,BUN,CRE or LDH-L levels among the 4 groups(P>0.05).Conclusion Combined treatment with pirfenidone and PD-L1 inhibitor significantly inhibits the progression of bladder cancer in mice possibly by regulating tumor immune microenvironment and inhibiting epithelial-mesenchymal transition of the tumor cells.

  Objective  To understand the current status of surgical treatment for hemophilia osteoarthropathy (HO) in China.  Methods  Using an online questionnaire, select domestic hospitals that partici-pated in the compilation of the 'Guideline for perioperative management of hemophilia patients undergoing orthopaedic surgery in China ', in addition to members of the National Joint Surgery Group, and the Orthopedic Branch of the Chinese Medical Association for targeted investigation and analysis.  Results  A total of 17 domestic hospitals were included, all of which were general hospitals. Hospitals that started HO surgery treatment before 2000 accounted for 35.29%. A total of 3057 surgical cases of HO were reported by those hospitals. The most commonly performed surgical procedures were hip and knee joint replacement. The most commonly used coagulation factor replacement regimen was recombinant coagulation factor preparation. Ten hospitals reported finding patients with transfusion-related infectious diseases. Bleeding and hematoma formation were the most frequently reported surgical complications. Excessive length of hospital stay and high economic costs were the most frequently reported problems.  Conclusions  Surgical treatment for HO in 17 hospitals is mainly carried out in some large comprehensive medical centers in the eastern region. Compared with the patient base, the popularity and number of surgeries are still relatively insufficient. It is necessary to further standardize the treatment system by standardizing factor replacement and strengthening rehabilitation to improve surgical treatment outcomes.

Objective    To explore the application of Tsetlin Machine (TM) in heart beat classification. Methods    TM was used to classify the normal beats, premature ventricular contraction (PVC) and supraventricular premature beats (SPB) in the 2020 data set of China Physiological Signal Challenge. This data set consisted of the single-lead electro-cardiogram data of 10 patients with arrhythmia. One patient with atrial fibrillation was excluded, and finally data of the other 9 patients were included in this study. The classification results were then analyzed. Results    The classification results showed that the average recognition accuracy of TM was 84.3%, and the basis of classification could be shown by the bit pattern interpretation diagram. Conclusion    TM can explain the classification results when classifying heart beats. The reasonable interpretation of classification results can increase the reliability of the model and facilitate people's review and understanding.

OBJECT IVE To evaluate the application effect of the whole cour se medication management mode led by pharmacists in rheumatic immune diseases. METHODS A total of 122 patients treated with tacrolimus or cyclosporine in the department of rheumatology and immunology of Wuhan No. 1 Hospital from 2018 to 2020 were selected as the study subjects. Among them ，44 cases in the control group were under the traditional supervision mode ；78 patients in the observation group adopted the whole course medication management mode led by pharmacists ，that was ，individual pharmacists and specialist clinical pharmacists cooperated and led ，and not only participated in the whole process of drug treatment but also involved in the whole process of therapeutic drug monitoring （TDM）. On the basis of the control group ，the division of labor and cooperation among medical，pharmaceutical and nursing parties were strengthened ，and the homogeneous supervision was carried out for the outpatients and inpatients from admission to discharge . The daily dose of medication ，the rate of reaching the standard of blood drug concentration ，the incidence of problematic samples （the sample was calculated by the number of times ），the average hospitalization days ，the re-admission rate within 6 months after discharge ，the medication compliance score and the patient ’s satisfaction rate were compared between the two groups. RESULTS In the control group ，53 times of TDM were performed ， including 18 times of tacrolimus monitoring and 35 times of cyclosporine monitoring ；in the observation group ，123 timesof TDM were performed ，including 55 times of tacrolimus monitoring and 68 times of cyclosporine monitoring. The daily dose of tacrolimus ，the daily dose of cyclosporine ，the rate of reaching the standard of cyclosporine blood drugconcentration，the inc idence of problematic samples ，the rate of re-admission within 6 months after discharge ， the medication compliance score and the patient ’s satisfaction rate in the observation group were significantly better than those in the control group （P＜0.05）. CONCLUSIONS It can effectively improve the effect of the quality of pharmaceutical care to implement whole course and homogeneous medication management led by pharmacists and provide precise drug guidance for patients with rheumatic and immune diseases.

Objective:To explore the characteristics of multimodal ultrasound before neoadjuvant chemotherapy (NAC) and the degree of postoperative pathological remission and B-cell lymphoma-2 (BCL-2) .Methods:From Jan. 2018 to Dec. 2020, female breast cancer patients who underwent breast-conserving or total mastectomy surgery at Shaanxi Hospital of traditional Chinese Medicine were selected as the research objects. Routine ultrasound, automatic breast full-volume imaging, and contrast-enhanced ultrasound were performed before chemotherapy. The postoperative pathological remission was evaluated according to Miller and Payne’s modified pathological response grading standard. The expression of BCL-2 in breast cancer tissue was detected by immunohistochemistry. Univariate analysis was performed on the characteristics of MHR, NMHR and bcl-2 with different expression status. Then, binary Logistic regression was used to analyze the significant variables in univariate analysis.Results:Among 186 patients, 84 patients (45.2%) were in MHR group and 102 patients (54.8%) in NMHR group after NAC surgery. The maximum diameter of mass in NMRH group was > 4 cm. The proportion of CM, irregular shape of mass, microcalcification, high enhancement of CEUS and perfusion defect (62.7%, 62.7%, 70.6%, 62.7%, 66.7%) was significantly higher than that of MRH group (38.1%, 40.5%, 39.3%, 41.7%, 31.0%, P<0.05) . The proportion of irregular shape, microcalcification, Alder blood flow grade 2-3, hyperenhancement and peripheral radiation enhancement in low bcl-2 expression patients (65.1%, 69.8%, 65.1%, 71.7%, 72.6%, respectively) was significantly higher than that in high Bcl-2 expression patients (36.2%, 38.7%, 27.5%, 28.7%, 38.8% respectively) (all P<0.05) . Multivariate Logistic analysis showed that irregular masses, with microcalcifications, and high CEUS performance were independent risk factors for NMHR (all P<0.05) ; irregular masses, with microcalcifications, and CEUS manifestations of peripheral radial enhancement were independent risk factors for low expression of BCL-2 (all P<0.05) . Conclusion:Multimodal ultrasound features can be used to predict the degree of pathological remission and the expression of BCL-2 in breast cancer patients with NAC, which helps to select treatment options and predict the prognosis of patients.

Objective To explore the effect of blended learning in practical training of acupuncture techniques.Methods Sophomores of acupuncture and Tuinaspeciality were divided into two groups based on classes,with 38 students in experimental group and 34 in control group,adopting blended learning and traditional method in teaching acupuncture techniques respectively.Blended learning mainly adopts mixed methods of both online "punch-card" on WeChat community and offline class learning.Post-test score of two groups were compared by independent samples t-test with SPSS 19.0.The teaching effect of blended learning was evaluated in students in experimental group by questionnaire survey.Results The total score of acupuncture techniques (4.73 ± 0.15) in experimental group were significantly higher than that of control group (4.27 ± 0.46) (t=5.588,P＜0.01) and students' satisfaction concerning the blended learning in experimental group was up to 88％ (22/25).Conclusion Blended learning can promote students' acupuncture skills and cultivate good study habits,making practice in class more targeted.More friendly online learning tools needs to be further developed.

Objective To investigate the effect of the different rehabilitation training method on the first ray of postoperative hallux valgus (HV). Methods Based on medical images of HV patient, a comprehensive three-dimensional finite element model of HV foot was established, including bones, sesamoid, cartilage, ligaments, soft tissues, Achilles tendon. The passive/active plantar flexion and dorsal flexion as well as standing were simulated to investigate the biomechanical behavior of distal osteotomy fragment of the postoperative HV. Results The stress distribution on distal osteotomy fragment during passive training was more uniform, and the peak stress (7.78 MPa) was greater than that during stance phase and active training. The distal osteotomy fragment displacement during passive training (0.98 mm) in anterior-posterior direction was greater than that during stance phase (0.69 mm) and active training (0.38 mm). Conclusions The passive training could promote the contact of osteotomy surface and reduce the healing time of osteotomy, which would be beneficial for rehabilitation of postoperative HV.

Objective:To evaluate the efficacy of intravitreal lucentis or conbercept injection combined with ahmed glaucoma valve (AGV)implantation on the treatment of neovascular glaucoma (NVG).Methods:A total of 68 NVG patients (68 eyes)were divided into three groups according to the pretreatment (the intravitreal injection of lucentis or conbercept or no intravitreal injection 3 - 7 d before AGV implantation):lucentis group (n = 26, given intravitreal injection of 10 g · L-1 lucentis),conbercept group (n = 21, given intravitreal injection of 10 g·L-1 conbercept)and control group (n=21,given medicine or puncture of anterior chamber to smoothen the IOP and received AGV implantation).The panretina photocoagnlation (PRP)was performed in the patients with clear ocular media before intravitreal injection or AGV implantation.For the patients with cloudy ocular media,the intravitreal injection of anti-VEGF drugs was performed first and the PRP was performed when fundus could be seen.Results:Compared with before operation,the mean IOP and the number of antiglaucoma medications of the patients used in three groups after operation were significantly decreased (P < 0.01).There were no significant differences in the successful rates of operation of the patients in three groups at different time points after operation (P >0.05).1 month and 3 months after operation,the BCVA of the patients in lucentis and conbercept groups was significantly better than that in control group (P <0.05).There were no significant differences in the incidence of complications of the pateints between lucentis and conbercept groups at different time points after operation (P >0.05).Conclusion:Intravitreal injection of anti-VEGF drugs combined with AGV implantation is effective and safe in the treatment of NVG.In short term,it can improve the vision,relieve the pain and reduce the complications.