Preliminary study on the mechanism of halofuginone inhibiting the activity of HepG2 cells / 药学学报

This study aimed to investigate halofuginone's inhibitory effect and mechanism on the activity of hepatocellular carcinoma cells. HepG2 cells were used to detect the effects of halofuginone. After treatment, cell activity, cell migration, cell cycle, and cell apoptosis were detected by CCK-8, transwell, and flow cytometry, respectively. The expression levels of growth and metabolism-related factors such as citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and isocitrate deoxygenase (IDH) were detected by real-time quantitative PCR and Western blot. Compared with the control group, the activity of HepG2 cells was significantly inhibited by halofuginone (P < 0.01), the migration rate of HepG2 cells was decreased (P < 0.01), the apoptosis of HepG2 cells was induced (P < 0.01), and the cell cycle was arrested in S phase (P < 0.01). The expression levels of tricarboxylic acid key enzymes CS, IDH3, and OGDH were up-regulated, the expression level of isocitrate dehydrogenase isoenzymes IDH1 and IDH2 were down-regulation. In conclusion, halofuginone can inhibit the proliferation and migration of HepG2 cells and promote apoptosis in a dose-dependent manner, which may be due to the promotion of the aerobic metabolism of cells.

Preparation of mouse monoclonal antibodies against the ectodomain of Western equine encephalitis virus E2 (E2ecto) protein / 细胞与分子免疫学杂志

Objective To prepare mouse monoclonal antibodies against the ectodomain of E2 (E2ecto) glycoprotein of Western equine encephalitis virus (WEEV). Methods A prokaryotic expression plasmid pET-28a-WEEV E2ecto was constructed and transformed into BL21 (DE3) competent cells. E2ecto protein was expressed by IPTG induction and presented mainly as inclusion bodies. Then the purified E2ecto protein was prepared by denaturation, renaturation and ultrafiltration. BALB/c mice were immunized with the formulated E2ecto protein using QuickAntibody-Mouse5W as an adjuvant via intramuscular route, boosted once at an interval of 21 days. At 35 days post-immunization, mice with antibody titer above 1×104 were inoculated with E2ecto intraperitoneally, and spleen cells were fused with SP2/0 cells three days later. Hybridoma cells secreting specific monoclonal antibodies were screened by the limited dilution method, and ascites were prepared after intraperitoneal inoculation of hybridoma cells. The subtypes and titers of the antibodies in ascites were assayed by ELISA. The biological activity of the mAb was identified by immunofluorescence assay(IFA) on BHK-21 cells which were transfected with eukaryotic expression plasmid pCAGGS-WEEV-CE3E2E1. The specificity of the antibodies were evaluated with E2ecto proteins from EEEV and VEEV. Results Purified WEEV E2ecto protein was successfully expressed and obtained. Four monoclonal antibodies, 3G6G10, 3D7G2, 3B9E8 and 3D5B7, were prepared, and their subtypes were IgG2c(κ), IgM(κ), IgM(κ) and IgG1(κ), respectively. The titers of ascites antibodies 3G6G10, 3B9E8 and 3D7G2 were 105, and 3D5B7 reached 107. None of the four antibody strains cross-reacted with other encephalitis alphavirus such as VEEV and EEEV. Conclusion Four strains of mouse mAb specifically binding WEEV E2ecto are successfully prepared.

Treatment advice of small molecule antiviral drugs for elderly COVID-19 / 中国药理学通报

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Clinical characteristics and drug efficacy evaluation of voltage-gated potassium channel-related genetic epilepsy / 中国药理学通报

Aim To analyze the genotype-phenotype characteristics of voltage-gated potassium channels (Kv) associated genetic epilepsy and evaluate the efficacy of anti-seizure medications(ASMs). Methods PubMed database was searched and patients meeting the inclusion criteria were included for analysis. We divided the patients into “benign”, “encephalopathic” and other phenotypes according to the clinical characteristics. We performed descriptive statistical analysis of patients' mutated genes, clinical phenotype and drug efficacy, and used logistic regression to explore the influencing factors of treatment outcome. Results Data of 474 children were included for analysis. There were significant differences among different phenotypes in mutated genes, source of mutations and so on. In terms of clinical characteristics, there were also significant differences between patients with different phenotypes in age of onset, combined developmental delay and so on. In terms of monotherapy, phenobarbital was the most common treatment choice for children with “benign” phenotype, and sodium channel blockers (SCBs) were the most common treatment choice for children with “encephalopathy” phenotype, and the efficacy of SCBs monotherapy was superior to that of other ASMs. Multivariate Logistic analysis of the children receiving monotherapy showed that whether the children were combined with developmental delay and whether SCBs were used were significant factors influencing the efficacy of drug therapy. Conclusions Patients with the “benign” and “encephalopathic” phenotypes differ in several aspects of genetic variation, clinical characteristics, and drug selection. These results suggest that SCBs may be one of the recommended options for monotherapy.

Chinese yam yield is affected by soil nutrient levels and interactions among N, P, and K fertilizers / 中草药·英文版

OBJECTIVE@#The current fertilization methods for Chinese yam are uneconomic and unfriend to environment. A rational one is very important to achieve desired balance of high yield of Chinese yam, economic and friend to environment. Here, we studied the effects of nitrogen (N), phosphorus (P), and potassium (K) fertilizers on the yield of 'Qinfeng' Chinese yam in shallow-groove directional cultivation.@*METHODS@#The experiments were conducted in Dehua County, Fujian Province, China using a "3414" optimal design. Overall, three fertilizer factors (N, P, and K) were evaluated at the following four levels: 0, no fertilizer; 1, 0.5-fold the typical rate; 2, typical fertilization rate; and 3, 1.5-fold the typical rate. There were 14 different fertilization treatments.@*RESULTS@#Treatment 6 (N2P2K2) produced the longest (75.6 cm) and thickest tubers (4.9 cm) with the highest tuber fresh weight (1311.9 g) and yield (41 015.9 kg/hm2), whereas, treatment 1 produced the shortest (65.6 cm) and thinnest tubers (3.9 cm) with the lowest fresh weight (953.4 g) and yield (28 532.8 kg/hm2) among the 14 fertilizer combinations. The experimental data could be fitted to single-variable quadratic and binary quadratic models but not to a ternary quadratic polynomial model. Appropriate N, P, and K fertilizer application rates increased Chinese yam yield. However, excessive fertilization lowered the yield. Chinese yam yield was significantly and strongly correlated with the amounts of N, P, and K fertilizer applied.@*CONCLUSION@#Based on the single variable quadratic and binary quadratic models, we propose that the quantities of N, P, and K fertilizer used to grow 1 hm2 'Qinfeng' Chinese yam should be 360-388.3, 90-100.95, and 416.3-675 kg, respectively.

Effects of staged acupuncture on endometrial receptivity and anxiety in patients with recurrent implantation failure of thin endometrium based on "thoroughfare vessel is the sea of blood" theory / 中国针灸

OBJECTIVE@#To compare the clinical efficacy between staged acupuncture based on "thoroughfare vessel is the sea of blood" theory combined with routine hormone replacement cycle treatment and routine hormone replacement cycle treatment for patients with recurrent implantation failure (RIF) of thin endometrium.@*METHODS@#A total of 72 RIF patients with thin endometrium were randomly divided into an observation group and a control group, 36 cases in each group. The patients in the control group were treated with routine hormone replacement cycle treatment. Based on the treatment of the control group, the patients in the observation group were treated with staged acupuncture based on "thoroughfare vessel is the sea of blood" theory. The main acupoints were Neiguan (PC 6) and Gongsun (SP 4), and the supplementary acupoints were selected according to the menstrual cycle and syndrome differentiation; the acupuncture was given once every other day, 3 times a week, for 3 consecutive menstrual cycles. The thickness and shape of endometrium, and Hamilton anxiety scale (HAMA) score were observed at implantation window before and after treatment; the clinical pregnancy rate, live birth rate and cycle cancellation rate were compared between the two groups; the correlation between endometrial thickness and HAMA score was analyzed.@*RESULTS@#Compared before treatment, the endometrial thickness in the two groups and the proportion of type A+B endometrium in the observation group were increased (P<0.05), and the HAMA scores in the two groups were decreased (P<0.05) after treatment. The above indexes in the observation group were superior to those in the control group (P<0.05). The clinical pregnancy rate and live birth rate in the observation group were higher than those in the control group (P<0.05), and the cycle cancellation rate was lower than that in the control group (P<0.05). There was a negative correlation between endometrial thickness and HAMA score (P<0.05).@*CONCLUSION@#Based on the routine hormone replacement cycle treatment, the addition use of staged acupuncture based on "thoroughfare vessel is the sea of blood" theory could improve the thickness and shape of endometrium, relieve anxiety, increase the clinical pregnancy rate and live birth rate, and reduce the cycle cancellation rate in RIF patients with thin endometrium. The curative effect is superior to the routine hormone replacement cycle treatment alone.

Validation of Pharyngeal Acid Reflux Episodes Using Hypopharyngeal Multichannel Intraluminal Impedance-pH

Background/Aims@#Hypopharyngeal multichannel intraluminal impedance-pH (HMII-pH) technology incorporating 2 trans-upper esophageal sphincter impedance channels has been developed to detect pharyngeal reflux. We used the HMII-pH technique to validate the candidate pharyngeal acid reflux (PAR) episodes based on the dual-pH tracings and determined the interobserver reproducibility. @*Methods@#We conducted a cross-sectional study in tertiary centers in Taiwan. Ninety patients with suspected laryngopharyngeal reflux and 28 healthy volunteers underwent HMII-pH test when off acid suppressants. Candidate PAR episodes were characterized by pharyngeal pH drops of at least 2 units and reaching a nadir pH of 5 within 30 seconds during esophageal acidification. Two experts manually independently identified candidate PAR episodes based on the dual-pH tracings. By reviewing the HMII-pH tracings, HMII-pH-proven PAR episodes were subsequently confirmed. The consensus reviews of HMII-pH-proven PAR episodes were considered to be the reference standard diagnosis. The interobserver reproducibility was assessed. @*Results@#A total of 105 candidate PAR episodes were identified. Among them 84 (80.0%; 95% CI, 71.0-87.0%) were HMII-pH-proven PAR episodes (82 in 16 patients and 2 in 1 healthy subject). Patients tended to have more HMII-pH-proven PAR episodes than healthy controls (median and percentile values [25th, 75th, and 95th percentiles]: 0 [0, 0, 3] vs 0 [0, 0, 0], P = 0.067). The concordance rate in diagnosing HMII-pH-proven PAR episodes between 2 independent observers was 92.2%. @*Conclusion@#Our preliminary data showed that 80.0% (71.0-87.0%) of the proposed candidate PAR episodes were HMII-pH-proven PAR episodes, among which the interobserver reproducibility was good.

More microinvasive foci in larger tumours of breast ductal carcinoma in situ

INTRODUCTION@#Microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. This study aimed to investigate the potential influence of Mi on survival and assess its correlations with clinicopathological parameters, prognosis and molecular markers.@*METHODS@#The number of Mi foci in a cohort of 66 DCIS-Mi cases was assessed from haematoxylin and eosin-stained sections. Disease-free survival, clinicopathological parameters and biomarker expression were correlated with the number of Mi foci.@*RESULTS@#Higher numbers of Mi foci were found in larger tumours (P = 0.031).@*CONCLUSION@#Greater extent of DCIS is associated with multifocal Mi.

Adjustable "paper clip" techniques suturing the dorsal vein complex in radical prostatectomy / 现代泌尿外科杂志

【Objective】 To investigate the efficacy of the adjustable "paper clip" techniques in the suture of dorsal vein complex (DVC) and retention of urethral function in robot-assisted laparoscopic radical prostatectomy (RALRP). 【Methods】 A total of 30 cases of prostate cancer treated with RALRP were enrolled, all of which used the adjustable "paper clip" techniques. During operation, the DVC was sewed with barbed suture, and then a reverse suture was made through two sides of the prostatic ligaments. A Hem-o-lock was used to fasten the suture, which would be flexible to control the degree of tightness for the ligature. Perioperative and follow-up data of urinary continence and symptoms were collected and analyzed. 【Results】 All operations were successful. The estimated blood loss was (123.3±80.7) mL, 53.6% patients recovered continence in 1 month, and the continence rate increased to 92.9% and 96.3% at month 3 and 6. 92.9 of patients had no risk of incontinence 3 months after surgery. 【Conclusion】 The adjustable "paper clip" techniques have advantages in reducing blood loss, maintaining clear surgical field, preserving urethral function, and improving urinary continence.

Comparison of yield of microorganisms in cord blood between two automated blood culture systems / 中国输血杂志

【Objective】 To compare the difference in the detection rate of microorganisms in cord blood between BACTEC FX and BacT/ALERT 3D automated blood culture systems, and to compare the influence of incubation time and different types of culture sample on the detection rate of microorganisms in cord blood. 【Methods】 Cord blood samples prepared from April to August 2020 in Sichuan Cord Blood Bank(n=4 358) were selected, and 20 mL of plasma was used as culture samples for microbial detection. In addition, cord blood samples prepared in the same months of 2021(n=4 057) were selected, and 19 mL of plasma plus 1 mL of final product was used as culture samples for microbial detection. The total sample size was 8 415, of which 4 849 samples(2 458 in plasma group and 2 391 in plasma plus final product group) were assigned to the BACTEC FX system, and 3 566 samples(1 900 in the plasma group and 1 666 in the plasma plus final product group) to the BacT/ALERT 3D system. All samples were cultured for 7 days, and culture data were recorded on day 5 and day 7. Positive results were confirmed by Gram staining. 【Results】 The positive rate detected by the BACTEC FX system was higher than that of the BacT/ALERT 3D system(4.08% vs 2.69%), with statistically significant difference(P0.05) detected by the BacT/ALERT 3D system. With quality control strains, there were significant differences in TTP between these two systems for Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Clostridium sporogenes, and Bacillus subtilis(P0.05). 【Conclusion】 This study suggests that the selection of BACTEC FX blood culture system with incubation time of not less than 7 days and plasma plus final product as culture samples may improve the detection rate of microorganisms in cord blood.

Efficacy of autologous ozoneized blood transfusion in improving motor function in convalescent stroke patients / 中国输血杂志

【Objective】 To investigate the efficacy of autologous ozoneized blood transfusion(AOBT) in improving consciousness and motor function in convalescent stroke patients. 【Methods】 A total of 44 patients who were diagnosed as convalescent cerebral apoplexy and received treatment in Rehabilitation Department of our hospital from August 2016 to September 2021 were randomly divided into the experimental group and control group by blind method. The experimental group (n=22) received general rehabilitation training (such as exercises, occupational therapy, acupuncture and transcranial magnetic stimulation) plus AOBT (200 mL venous phlebotomy at the median elbow), once every 2 to 3 days and 12 occasions as a course of treatment; the control group solely recieved general rehabilitation training. The consciousness (GCS score) and ability of daily living (Barthel index score) score of the two groups before and after treatment were statistically compared, and Ueda motor function grade, Brunnstrom stage and muscle tone grade were observed and evaluated. 【Results】 After the treatment, the experimental group and the control were compared as follows: 1) the GCS score and Barthel score was 14.82±0.39 vs 12.41±2.52, 61.14±12.24 vs 52.05±11.72(P<0.05); 2) The recovery rate of motor function was 95.45% (21/22) vs 63.64% (14/22) (P<0.05); 3) The total recovery rate of muscle tone was 90.91% (20/22) vs 63.64% (14/22) (P<0.05). 【Conclusion】 AOBT, with somewhat high safety and effectiveness, can improve the state of consciousness, motor function and muscle tone in convalescent patients with stroke.

Study on platelet components production in 19 provincial blood centers in China before and during the COVID-19 epidemic / 中国输血杂志

【Objective】 To study the changes of platelet components(PC), apheresis platelets (AP) and pooled platelet concentrates (PPC) production of 19 provincial blood centers before and during the COVID-19 epidemic. 【Methods】 The data related to the collection of AP and the preparation of PPC from 2016 to 2021 of 19 provincial blood centers was collected. The production of PC, AP and PPC during the four years before the epidemic (i.e. 2016-2019) and during the COVID-19 epidemic (i.e. 2020 and 2021) were calculated respectively, and the change of production was analyzed. 【Results】 The total production of PC in 19 blood centers steadily increased from 2016 to 2019, with a decrease of 4.16% in 2020 and an increase of 15.60% in 2021, exceeding the output before the COVID-19 epidemic. In 2020, the production of PC of 42.11% (8/19) blood centers decreased compared with 2019, while 94.74% (18/19) in 2021 increased compared with 2020. The changes of AP output was basically consistent with the trend of PC. The total production of PPC in 2017 and 2018 both doubled compared to the previous year, while decreased by 67.98% in 2019, increased by 30.38% in 2020 and decreased by 27.08% in 2021. 【Conclusion】 The total production of PC kept increasing steadily between 2016 and 2019, but decreased in 2020 under the COVID-19 epidemic, with some blood centers being significantly affected. In 2021, with the strong support from government and various measures by blood centers, the total production of PC increased.

Effectiveness and safety of transcatheter aortic valve replacement in treatment of aortic regurgitation: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To investigate effectiveness and safety of transcatheter aortic valve replacement in the treatment of aortic regurgitation. Methods     PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Wanfang Data and VIP were searched from inception to August 2021. According to the criteria of inclusion and exclusion, two reviewers independently screened the literature, extracted the data and evaluated the quality of the included studies. Then, Stata 16.0 software was used for meta-analysis. Subgroup meta-analysis of valve type used and study type was performed. Results    Twenty-five studies (12 cohort studies and 13 single-arm studies) were included with 4 370 patients. Meta-analysis results showed that an incidence of device success was 87% (95%CI 0.81-0.92). The success rate of the new generation valve subgroup was 93% (95%CI 0.89-0.96), and the early generation valve subgroup was 66% (95%CI 0.56-0.75). In addition, the 30-day all-cause mortality was 7% (95%CI 0.05-0.10), the 30-day cardiac mortality was 4% (95%CI 0.01-0.07), the incidence of pacemaker implantation was 10% (95%CI 0.08-0.13), and the incidence of conversion to thoraco-tomy was 2% (95%CI 0.01-0.04). The incidence of moderate or higher paravalvular aortic regurgitation was 6% (95%CI  0.03-0.09). Conclusion     Transcatheter aortic valve replacement for aortic regurgitation is safe and yields good results, but some limitations can not be overcome. Therefore, multicenter randomized controlled trials are needed to confirm our results.

S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer / 中国结合医学杂志

OBJECTIVE@#To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research.@*METHODS@#The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified.@*RESULTS@#Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B (NF- κ B) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF- κ B was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF- κ B, the main therapeutic target.@*CONCLUSION@#YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.

Effect of Wenyang Zhenshuai Granules on autophagy and apoptosis of myocardial cells in septic rats via regulating miR-132-3p/UCP2 expression / 中国中药杂志

This study aimed to investigate the effect of Wenyang Zhenshuai Granules(WYZSG) on autophagy and apoptosis of myocardial cells in rats with sepsis via regulating the expression of microRNA-132-3p(miR-132-3p)/uncoupling protein 2(UCP2). Sixty SD rats were randomly divided into modeling group(n=50) and sham operation group(n=10). The sepsis rat model was constructed by cecal ligation and perforation in the modeling group. The successfully modeled rats were randomly divided into WYZSG low-, medium-and high-dose groups, model group and positive control group. Rats in the sham operation group underwent opening and cecum division but without perforation and ligation. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of rat myocardial tissue. Myocardial cell apoptosis was detected by TdT-mediated dUTP nick end labeling(TUNEL) assay. Real-time quantitative polymerase chain reaction(RT-qPCR) was performed to detect the expression of miR-132-3p and the mRNA expressions of UCP2, microtubule-associated protein light chain 3(LC3-Ⅱ/LC3-Ⅰ), Beclin-1 and caspase-3 in rat myocardial tissue. The protein expressions of UCP2, LC3-Ⅱ/LC3-Ⅰ, Beclin-1 and caspase-3 in myocardial tissue were detected by Western blot. Dual luciferase reporter assay was used to verify the regulatory relationship between miR-132-3p and UCP2. The myocardial fibers of sepsis model rats were disordered, and there were obvious inflammatory cell infiltration as well as myocardial cell edema and necrosis. With the increase of the WYZSG dose, the histopathological changes of myocardium were improved to varying degrees. Compared with the conditions in the sham operation group, the survival rate and left ventricular ejection fraction(LVEF) of rats in the model group, positive control group and WYZSG low-, medium-and high-dose groups were decreased, and the myocardial injury score and apoptosis rate were increased. Compared with the model group, the positive control group and WYZSG low-, medium-and high-dose groups had elevated survival rate and LVEF, and lowered myocardial injury score and apoptosis rate. The expression of miR-132-3p and the mRNA and protein expressions of UCP2 in myocardial tissue in the model group, positive control group and WYZSG low-, medium-and high-dose groups were lower, while the mRNA and protein expressions of LC3-Ⅱ/LC3-Ⅰ, Beclin-1 and caspase-3 were higher than those in the sham operation group. Compared with model group, the positive control group and the WYZSG low-, medium-and high-dose groups had an up-regulation in the expression of miR-132-3p and the mRNA and protein expressions of UCP2, while a down-regulation in the mRNA and protein expressions of LC3-Ⅱ/LC3-Ⅰ, Beclin-1 and caspase-3. WYZSG inhibited excessive autophagy and apoptosis of myocardial cells in septic rats and improved myocardial injury, possibly by regulating the expression of miR-132-3p/UCP2.

Efficacy and safety of Regan Syrup in treatment of common cold (wind-heat syndrome):a multicenter, randomized, double-blind, double-dummy, placebo and positive drug-controlled, parallel, phase Ⅱb clinical trial / 中国中药杂志

Regan Syrup has the effect of clearing heat, releasing exterior, benefiting pharynx and relieving cough, and previous phase Ⅱ clinical trial showed that the efficacy of Regan Syrup high-dose and low-dose groups was better than that of the placebo group, and there was no statistically significant difference in the safety between the three groups. The present study was conducted to further investigate the efficacy and safety of the recommended dose(20 mL) of Regan Syrup in the treatment of common cold(wind-heat syndrome). Patients who met the inclusion and exclusion criteria were selected and divided into the test group(Regan Syrup+Shufeng Jiedu Capsules placebo), positive drug group(Regan Syrup placebo+Shufeng Jiedu Capsules) and placebo group(Regan Syrup placebo+Shufeng Jiedu Capsules placebo) at a 1∶1∶1 using a block randomization method. The course of treatment was 3 days. A total of 119 subjects were included from six study centers, 39 in the test group, 40 in the positive drug group and 40 in the placebo group. The onset time of antipyretic effect was shorter in the test group than in the placebo group(P≤0.01) and the positive drug group, but the difference between the test group and the positive drug group was not significant. The test group was superior to the positive drug group in terms of fever resolution(P<0.05), and had a shorter onset time of fever resolution than the placebo group, but without obvious difference between the two groups. Compared to the positive drug group, the test group had shortened disappearance time of all symptoms(P≤0.000 1). In addition, the test group was better than the positive drug group and the placebo group in relieving symptoms of sore throat and fever(P<0.05), and in terms of clinical efficacy, the recovery rate of common cold(wind-heat syndrome) was improved in the test group compared to that in the placebo group(P<0.05). On the fourth day after treatment, the total TCM syndrome score in both test group and positive drug group was lower than that in the placebo group(P<0.05). There was no significant difference in the incidence of adverse events between three groups and none of them experienced any serious adverse events related to the study drug. The results indicated that Regan Syrup could shorten the onset time of antipyretic effect, reduce the time of fever resolution, alleviate the symptoms such as sore throat and fever caused by wind-heat cold, reduce the total score of Chinese medicine symptoms, and improve the clinical recovery rate with good safety.

Research progress on the mechanism of pain related neural pathways above the spinal cord / 生理学报

Pain is a multi-dimensional emotional experience, and pain sensation and pain emotion are the two main components. As for pain, previous studies only focused on a certain link of the pain transmission pathway or a certain key brain region, and there is a lack of evidence that connectivity of brain regions is involved in pain or pain regulation in the overall state. The establishment of new experimental tools and techniques has brought light to the study of neural pathways of pain sensation and pain emotion. In this paper, the structure and functional basis of the neural pathways involved in the formation of pain sensation and the regulation of pain emotion in the nervous system above the spinal cord level, including thalamus, amygdala, midbrain periaqueductal gray (PAG), parabrachial nucleus (PB) and medial prefrontal cortex (mPFC), are reviewed in recent years, providing clues for the in-depth study of pain.

A retrospective study on manual reduction combined with Chinese Orthopaedic ankle external fixator in the treatment of trimalleolar fracture / 中国骨伤

OBJECTIVE@#To evaluate the needle puncture safety and clinical efficacy of manual reduction combined with external fixation of ankle frame in the treatment of trimalleolar fracture under the guidance of Chinese Osteosynthesis (CO) theory.@*METHODS@#The clinical data of 118 patients with trimalleolar fractures admitted from December 2010 to December 2021 were retrospectively analyzed. Fifty-three patients were treated with manual reduction combined with external fixation of ankle frame(observation group). Sixty-five patients were treated with open reduction and internal fixation with plate and screws(control group). The operation time, hospitalization days, non-weight-bearing time of the affected limb, clinical healing time of fracture, incidence of complications, visual analogue scale (VAS) before and 1 month after operation, and American Orthopedic Foot and Ankle Society(AOFAS) score of ankle joint before and 1 year after operation were compared between the two groups.@*RESULTS@#Patients in both groups were followed up for more than 1 year. All patients were followed up, and the duration ranged from 14 to 70 months, with an average of(35.28±14.66) months. There were statistically significant in operation time, hospitalization days, non-load-bearing time of affected limbs, clinical healing time of fractures and VAS score one month after operation between the two groups. One month after operation, the VAS score of the observation group was lower than that of the control group(t=3.343, P=0.001). The operation time of the observation group was significantly shorter than that of the control group(t=9.091, P=0.000). The hospitalization days in the observation group were significantly less than those in the control group(t=5.034, P=0.000). The non-load-bearing time of the affected limb in the observation group was significantly shorter than that in the control group(t=11.960, P=0.000). The clinical healing time of fracture in the observation group was significantly shorter than that in the control group(t=4.007, P=0.000). There was no significant difference in AOFAS score between the two groups one year after operation(t=0.417, P=0.678). In the observation group, there were 2 cases of pinhole infection and 3 cases of loss of reduction less than 2 mm. There were 3 cases of surgical incision infection in the control group. There was no significant difference in the incidence of complications between the two groups(χ2=0.446, P=0.504).@*CONCLUSION@#Manual reduction combined with external fixation is safe and effective in the treatment of trimalleolar fracture under the guidance of CO theory, and the function of ankle joint recovers well after operation. This therapy has good clinical value.

Mechanism of bilobalide promoting neuroprotection of macrophages / 中国中药杂志

This study aims to explore the neuroprotective effect of bilobalide(BB) and the mechanisms such as inhibiting inflammatory response in macrophage/microglia, promoting neurotrophic factor secretion, and interfering with the activation and differentiation of peripheral CD4~+ T cells. BB of different concentration(12.5, 25, 50, 100 μg·mL~(-1)) was used to treat the RAW264.7 and BV2 cells for 24 h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay and cell counting kit-8(CCK-8) were employed to detect the cytotoxicity of BB and appropriate concentration was selected for further experiment. Lipopolysaccharide(LPS) was applied to elicit inflammation in RAW264.7 and BV2 cells, mouse bone marrow-derived macrophages(BMDMs), and primary microglia, respectively. The effect of BB on cell proliferation and secretion of inflammatory cytokines and neurotrophic factors was detected by enzyme-linked immunosorbent assay(ELISA). Spleen monocytes of C57BL/6 female mice(7-8 weeks old) were isolated, and CD4~+ T cells were separated by magnetic beads under sterile conditions. Th17 cells were induced by CD3/CD28 and the conditioned medium for eliciting the inflammation in BMDMs. The content of IL-17 cytokines in the supernatant was detected by ELISA to determine the effect on the activation and differentiation of CD4~+ T cells. In addition, PC12 cells were incubated with the conditioned medium for eliciting inflammation in BMDMs and primary microglia and the count and morphology of cells were observed. The cytoto-xicity was determined by lactate dehydrogenase(LDH) assay. The result showed that BB with the concentration of 12.5-100 μg·mL~(-1) had no toxicity to RAW264.7 and BV2 cells, and had no significant effect on the activity of cell model with low inflammation. The 50 μg·mL~(-1) BB was selected for further experiment, and the results indicated that BB inhibited LPS-induced secretion of inflammatory cytokines. The experiment on CD4~+ T cells showed that the conditioned medium for LPS-induced inflammation in BMDMs promoted the activation and differentiation of CD4~+ T cells, while the conditioned medium of the experimental group with BB intervention reduced the activation and differentiation of CD4~+ T cells. In addition, BB also enhanced the release of neurotrophic factors from BMDMs and primary microglia. The conditioned medium after BB intervention can significantly reduce the death of PC12 neurons, inhibit neuronal damage, and protect neurons. To sum up, BB plays a neuroprotective role by inhibiting macrophage and microglia-mediated inflammatory response and promoting neurotrophic factors.