Mitochondria are the main site of energy metabolism in cardiomyocytes， and at the same time mediate apoptosis and immune response， so mitochondrial dysfunction is closely related to the development of heart failure. Combined with the pathogenesis of mitochondrial dysfunction and heart failure， it is proposed that the mitochondrial function is similar to "sweat pore - collaterals - zang and fu organs"， according to which the treatment of heart failure is based on the theory of "sweat pore - collaterals - zang and fu organs". It is believed that the core mechanism of heart failure is qi deficiency， and qi deficiency leads to the weakness of the sweat pore opening and closing， or even the sweat pore closure， then resulting in qi deficiency and blood stasis， collaterals stagnation fail to flourish， and qi， blood， and body fluids can not infiltrate and nourish zang-fu organs， so that the heart fail to be nourished， and the disease will develop. The treatment should be based on the method of boosting qi and opening sweat pore， using acridity to unblock the collaterals， and invigorating blood and draining water， with medicinal of boosting qi， invigorating blood， and draining water as treatment.

Objective To observe the effects of electroacupuncture on the motor function and expressions of Irisin,Decorin and Myostatin in skeletal muscle of SAMP8 mice;To explore the mechanism of electroacupuncture in the treatment of the motor dysfunction of Alzheimer disease(AD).Methods Totally 247-month-old male SAMP8 mice were randomly divided into model group and electroacupuncture group,with 12 mice in each group,and the 12 male SAMR1 mice with the same age were set as the control group."Baihui","Dazhui"and"Shenshu"were selected in the electroacupuncture group,once a day,8 days as one course of treatment,with an interval of 2 days,for a total of 3 courses.The control group and the model group were not intervened.The motor function of mice was tested by grip strength test,pole climbing test and open field test,the mRNA expressions of Irisin,Decorin and Myostatin in quadriceps muscle were detected by RT-qPCR,and the protein expressions of Irisin,Decorin and Myostatin in quadriceps muscle were detected by immunohistochemistry and Western blot.Results Compared with the control group,the grip peak and duration of the mice in the model group decreased,head turning time and pole climbing time were prolonged(P<0.01),the mRNA and protein expressions of Irisin and Decorin decreased(P<0.05,P<0.01),and the expressions of Myostatin mRNA and protein increased(P<0.05).Compared with the model group,the grip peak and duration of the mice in the electroacupuncture group increased,head turning time and pole climbing time were decreased(P<0.05),the mRNA and protein expressions of Irisin and Decorin increased(P<0.05),and the expressions of Myostatin mRNA and protein decreased(P<0.05).Conclusion Electroacupuncture can improve the motor dysfunction of SAMP8 mice,and its mechanism may be related to regulating the expressions of Irisin,Decorin and Myostatin in skeletal muscle.

Objective:To explore the challenges in the implementation of drug centralized volume-based procurement policies in hospitals and propose corresponding optimization suggestions.Methods:From August to December 2023, a purposive sampling was conducted to select 11 pharmaceutical experts from tertiary hospitals in China for Delphi method. The survey content included " policy recommendations for promoting the acceleration and expansion of national drug centralized procurement and retaining surplus medical insurance funds for centralized procurement" .Results:Survey participants gave feedback on a set of existing problems found in the implementation of drug centralized procurement policies and proposed corresponding optimization methods. Kendall′s W coefficient of the specialist consultation was 0.332( P<0.05), demonstrating good consistency and concentration of the expert opinions. Among the problems, the score of drug supply guarantee was the highest(mean value of importance was 4.45). At the same time, the recommendation of strengthening monitoring and early warning, coordination and dispatch, and effectively ensuring the supply of centralized drug procurement had the highest score and concentration(mean value of importance was 4.91, coefficient of variation was 0.06). Conclusions:Through Delphi method, this study revealed issues and optimization methods in the implementation of drug centralized procurement policies in hospitals. The findings could provide valuable insights for improvements in the pharmaceutical sector and future policy adjustments.

Objective:Through meta-analysis, the association of three common adipokines (leptin, adiponectin, and chemerin) with bone nutrition of senile osteoporosis (SOP) in China was systematically evaluated.Methods:CNKI, CBM, VIP, Wanfang, PubMed, Web of Science, Embase, Cochrane Library, and other databases were searched for articles published from the establishment of the database to July 30, 2022. After literature screening, data extraction, and quality evaluation of the included studies were independently conducted by two researchers, a meta-analysis was performed using RevMan5.4 and Stata17.0 softwares.Results:A total of 13 studies in the Chinese population were included, including 897 patients with SOP and 673 elderly with normal bone mineral density . The results of the meta-analysis showed that compared with the control group, the serum leptin levels were significantly lower ( MD -2.64, 95% CI -4.04 to -1.23, P < 0.001), chemerin levels were significantly higher ( MD 25.23, 95% CI 14.57 to 35.90, P < 0.001), and adiponectin levels were not significantly different ( MD -0.55, 95% CI -2.26 to 1.17, P > 0.05) in SOP patients. After subgroup analysis according to the measurement method, leptin levels remained lower in SOP patients than in the control group. Conclusions:Compared with the control group, leptin levels were lower and chemerin levels were higher in SOP patients. Therefore, dysregulation of adipokines may play an important role in the occurrence and development of SOP, and regulation of adipokine levels and functions may play a role in the treatment of SOP and the improvement of bone nutrition as a nutritional intervention.

Background::Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays. Methods::Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed. Results::The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) ( χ2 = 19.83, P < 0.001), serum BDG (≥70 pg/mL: 33% [31/95]) ( χ2 = 24.65, P < 0.001), and fungal culture (33% [84/253]) ( χ2 = 29.38, P < 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher’s exact P = 1.000) to and slightly lower specificity (87% [77/89]) ( χ2 = 5.52, P = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812-0.953]) and BAL GM (0.901 [0.824-0.977]) ( P = 0.734). Sputum LFD had similar specificity (91% [81/89]) ( χ2 = 0.89, P = 0.345) to and lower sensitivity (63% [24/38]) ( χ2 = 4.14, P = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) ( χ2 = 6.95, P = 0.008), BDG ( χ2 = 10.43, P = 0.001), and fungal culture ( χ2 = 12.70, P < 0.001). Conclusions::Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.

Objective:To explore the use of internet-based continuous visual recognition task (MemTrax test, MTX) as a rapid screening tool for amnestic mild cognitive impairment (aMCI).Methods:Sixty-four patients with aMCI and 64 individuals with normal cognition as healthy controls were enrolled respectively from Department of Neurology and Health Examination Center of the First Affiliated Hospital of Kunming Medical University from August 2018 to December 2019. Montreal Cognitive Assessment (MoCA) scale and MTX were adopted to assess the cognitive function of all subjects. The total adjusted MoCA scale score, correct rate of MTX, reaction time of MTX and MTX score were obtained and statistically analyzed.Results:The adjusted MoCA scale scores of aMCI patients and healthy controls were 19 (14, 24) and 26 (24, 27; Z=6.795), the correct rate of MTX of aMCI patients and healthy controls were 74% (60%, 80%) and 88% (84%, 94%; Z=8.359), and the MTX score of aMCI patients and healthy controls were 51.11±14.07 and 70.56±14.91 ( t=7.590), respectively, all with statistically significant difference ( P<0.001). Reaction time of MTX of aMCI patients and healthy controls was 1.401 (1.253, 1.590) s and 1.277 (1.163, 1.410) s, respectively ( Z=3.083, P<0.01). After adjustment for age, physical or mental occupation, exercise, hypertension, hyperlipidemia, stroke, sleep time, as well as smoke, the linear regression showed that the aMCI patients had a significant decrease of adjusted MoCA score, correct rate of MTX and MTX score ( P<0.001), and an extension of reaction time of MTX ( P=0.071), compared with the controls. By MTX and MoCA scale assessment, the best cutoff value was 81% for correct rate of MTX and 23 for adjusted MoCA scale score respectively for the prediction of aMCI (with sensitivity of 79.7%, 93.8% respectively, and specificity of 68.8%, 82.8% respectively). The area under the curve (AUC) of correct rate of MTX was 0.93 (95% CI 0.89-0.97, P<0.001), and the AUC of adjusted MoCA score was 0.85 (95% CI 0.78-0.91, P<0.001). There was a statistically significant difference in paired comparison of the two AUCs (χ2=4.620, P<0.05). Conclusion:MTX acts better for the detection of aMCI than MoCA scale, and correct rate of MTX<81% can be considered as the existence of MCI.

Scaffold-free tissue engineered cell sheet is an emerging technology in biomedical field. It can avoid the adverse effects of scaffold materials, and can be further assembled to form more complex three-dimensional functional tissues. The construction of cell sheet is mainly based on the culture substrate composed of sensitive materials. By changing the stimulation factors such as temperature, enzyme, light, ion, redox, pH and sugar, the adhesion behavior of the substrate to the cells could be changed to make the cells detach naturally, thus generating the cell sheet. Recent years have seen the development of various simple and efficient construction technologies of cell sheet due to the development of a variety of novel sensitive culture substrates. The resulted cell sheets with excellent performance have greatly expanded their applications. This review summarized the construction methods of tissue engineered cell sheet and discussed the challenges and future perspectives in this field.
Temperature ; Tissue Engineering ; Tissue Scaffolds

OBJECTIVE: To investigate the effect of calmodulin (CaM) and its mutants on binding to voltage-gated Na channel isoleucine-glutamine domain (Na1.2 IQ). METHODS: The cDNA of Na1.2 IQ was constructed by PCR technique, CaM mutants CaM, CaM and CaM were constructed with Quickchange site-directed mutagenesis kit (QIAGEN). The binding of Na1.2 IQ to CaM and CaM mutants under calcium and calcium free conditions were detected by pull-down assay. RESULTS: Na1.2 IQ and CaM were bound to each other at different calcium concentrations, while GST alone did not bind to CaM. The binding affinity of CaM and Na1.2 IQ at [Ca]-free was greater than that at 100 nmol/L [Ca] ( < 0.05). In the absence of calcium, the binding amount of CaM wild-type to Na1.2 IQ was greater than that of its mutant, and the binding affinity of CaM to Na1.2 IQ was the weakest among the three mutants ( < 0.05). CONCLUSIONS The binding ability of CaM and CaM mutants to Na1.2 IQ is Ca-dependent. This study has revealed a new mechanism of Na1.2 regulated by CaM, which would be useful for the study of ion channel related diseases.
Calcium ; metabolism ; Calmodulin ; genetics ; metabolism ; Mutation ; NAV1.2 Voltage-Gated Sodium Channel ; metabolism ; Protein Binding ; genetics

[Abstract] Objective: To screen candidate epitopes of breast cancer HLA-A2 restrictive neoantigen and to identify high frequency mutation sites in breast cancer neoantigen by using bioinformatics method. Methods: NCBI and GDC databases were used to search missense mutation sites formed by single nucleotide mutation in breast cancer among reported literatures and sequencing data. The new antigen epitopes were predicted by HLA-A2 antigen epitope prediction website BIMAS, SYFPEITHI and artificial neural networkbased NetMHC4.0, and the epitopes with TAP binding power less than Intermediate were eliminated. The candidate epitopes were prioritized by mutation frequency and prediction results. Results: A total of 17 high-frequency mutation genes, including BTLA, ERBB2 and NBPF12 etc, were screened by the above-mentioned methods, and a total of 26 neoantigen epitopes were identified. The binding power of epitopes predicted using BIMAS and SYFPEITHI showed great difference (P<0.05), epitopes in high priority as GSTP1 (A114V , mutation frequency of 5.94%) and BRCA2 (N991H, mutation frequency of 5.40%) etc, were expected to be candidate neo-antigen epitopes; however, their mutation frequency was relatively too low to achieve“universal use” . The possibility of these epitopes used as general breast cancer neo-antigen epitopes is less likely. Conclusion: The common mutation frequency of breast cancer is lower than that of other tumors; it ’s difficult to find“universal”new antigen epitopes of breast cancer; the individualized neoantigen vaccine may be of more promise, which needs further research.

Objective: To investigate the safety and feasibility of laparoscopic operation in thetreatment of gastric gastrointestinal stromal tumor (GIST) at unfavorable positions. Methods: A retrospective cohort study was conducted to analyze the clinical data of patients with gastric GIST at unfavorable positions confirmed by pathology after surgery (laparoscopy or laparotomy) at the Southwest Hospital of the Army Medical University and the Minda Hospital of Hubei Minzu University from June 2008 to June 2018. The unfavorable positions of stomach are defined as the esophagogastric junction, the proximal cardia of gastric lesser curvature, the pylorus of stomach, the posterior wall of stomach and the antrum of stomach.Exclusion criteria:(1) preoperative chemotherapy or imatinib therapy; (2) diameter of tumor > 10 cm; (3) tumor metastasis or concurrence of other malignant tumors. A total of 244 patients (238 in Southwest Hospital and 6 in Minda Hospital) were enrolled, including 122 males and 122 females with age of 41-70years. Operative methods should be adopted according to patients' wishes. There were 146 cases in the laparoscopic surgery group and98 cases in the open surgery group. The intraoperative blood loss, operative time, postoperative first flatus time, postoperative firstfeeding time,average hospital stay, morbidity of postoperative complication,1-,3-,and 5-year recurrence free survival(RFS) and overall survival (OS)rate were compared between the two groups. Results: There were no significant differences in sex, age, tumor size, tumor risk grade or growth pattern between the laparoscopic and the open surgery groups (all P>0.05),and these two groups were comparable. Compared with open group, laparoscopic group had less intraoperative blood loss [(31.4±2.3) ml vs. (143.9±3.7) ml, t=292.800, P<0.001], shorter postoperative first flatus time [(2.1±0.7) days vs.(3.8±0.8) days, t=17.550,P<0.001], shorter postoperative first feeding time [(2.1±0.5) days vs.(2.3±1.7) days, t=1.339,P=0.020], shorter hospital stay [(8.6±2.6) days vs. (13.6±3.2) days, t=13.410, P<0.001], and lower morbidity of postoperative complication [16(11.0%) vs. 21(21.4%),χ²=4.996,P=0.025], whose differences were statistically significant. While the operation time was similar in two groups [(124.7±15.8) minutes vs. (120.9±14.5) minutes, t=1.903,P=0.058]. The median follow-up of all the patients was 43 (1 to 119) months.In laparoscopic group and open group, the 1-, 3- and 5-year RFS were 94.5% vs. 93.9%, 91.1% vs. 90.8%,and 82.2% vs. 81.6%, respectively, and 1-, 3- and 5-year OS were 98.6% vs. 95.9%, 95.9% vs. 94.9%,and 91.1% vs. 88.8%, respectively, whose differences were not statistically significant (all P>0.05). Conclusion In the experienced gastrointestinal surgery center, laparoscopic resection of gastric GIST at unfavorable position is safe and feasible, achieving the same efficacy of open surgery.