Efficacy of Zhumian Tang formula granules combined with eszopiclone for the treatment of poor sleep quality: a multi-center, randomized controlled, superiority trial.

OBJECTIVE: To evaluate the efficacy and safety of Zhumian Tang formula granules combined with eszopiclone for treating poor sleep quality. METHODS: This multi-center, dynamic block-randomized, parallel-group superiority clinical trial included 130 patients. The combined treatment group received Zhumian Tang formula granules combined with eszopiclone treatment, and the control group received eszopiclone treatment only. The group allocation ratio was 1∶1. The duration of treatment was 2 weeks. Participants were asked to complete questionnaires before treatment, after 1 week of the intervention, after 2 weeks of the intervention, and at the follow-up on week 3. The primary outcomes were the Pittsburgh Sleep Quality Index (PSQI) score and the total effective rate of treatment. The secondary outcome was the rate of adverse effects. RESULTS: Compared with the eszopiclone treatment group, the PSQI score of the combined treatment group was significantly lower after 2 weeks of the intervention (6.98 vs 8.26, P < 0.05). However, there was no significant difference in the mean PSQI score after 1 week of the intervention (9.89 vs 9.15, P = 0.124). After the follow-up on week 3, the PSQI score of the combined treatment group remained significantly lower than that of the eszopiclone treatment group (6.12 vs 8.31, P < 0.001). The total effective rates of treatment of the combined group and the eszopiclone group were 36.92% vs 35.38% (Z = 0.033, P = 0.855) after 1 week of the intervention, 83.08% vs 58.46% (Z = 9.519, P < 0.05) after 2 weeks of the intervention, and 83.08% vs 61.54% (Z = 7.530, P < 0.05) and after the follow-up on week 3, respectively. There was no significant difference in the overall rate of adverse reactions between the combined and eszopiclone treatment groups (21.53% vs 31.8%, P = 0.318). CONCLUSION: The combination of Zhumian Tang formula granules with eszopiclone was found to be safe and more effective in improving sleep quality than eszopiclone alone. Traditional Chinese medicine can enhance the effectiveness of Western medicine in the treatment of insomnia.

Seasonal characteristics of scarlet fever in Songjiang District, Shanghai in 2012-2021 / 公共卫生与预防医学

Objective To analyze the seasonal characteristics of scarlet fever in Songjiang District from 2012 to 2021, and to provide references for the prevention and control of scarlet fevers. Methods The incidence data of scarlet fever in Songjiang District from 2012 to 2021 were collected through the China Disease Prevention and Control Information System. The seasonal characteristics and peak of scarlet fever incidence were analyzed using concentration and circular distribution methods. Results The average annual reported incidence rate of scarlet fever in Songjiang District from 2012 to 2021 was 20.15/100 000. The M value of the concentration analysis was 0.18. The results of the circular distribution method showed that the peak day of scarlet fever from March to August was May 12, and the epidemic peak period was from April 3 to June 20. From September to February of the next year, the peak day of scarlet fever was December 21, and the epidemic peak period was from December 2 to January 9 of the next year. The differences were all statistically significant (P values were all less than 0.05). Conclusion The peaks of scarlet fever in Songjiang District mainly occur in May and December. It is suggested that the monitoring methods and prevention strategies should be adjusted in time according to Seasonal characteristics of scarlet fever.

A new xanthone from the Polygala tenuifolia Willd. of northern Shaanxi / 药学学报

Ten compounds were isolated and purified from ethanol extracts of dried roots bark of Polygala tenuifolia Willd. by various chromatography techniques such as silica gel and Sephadex LH-20. Their structures were identified by analysis of physicochemical properties and spectral data, and determined as β-sitosterol (1), tenuifolin (2), 6-methoxy coumarin (3), 7-phenyl-1-hydroxy-2,3,6-trimethoxyxanthone (4), 1,8-dihydroxy-3,4,7-trimethoxyanthone (5), mangiferin (6), quercetin-3-O-β-D-glucoside (7), rutin (8), syringaldehyde (9), salicylicacid (10). Among them, compounds 3, 4 and 5 were isolated from the genus of Ploygala for the first time and compound 4 was a new xanthone. The acetylcholinesterase inhibitory activities of compounds 3, 4 and 5 were evaluated by Ellman colorimetric method, compounds 3 and 5 exhibited moderate inhibitory activity, compound 4 exhibited weak inhibitory activity.

Increased development of T-bet+CD11c+ B cells predisposes to lupus in females: Analysis in BXD2 mouse and genetic crosses.

Cardinal features of lupus include elevated B cell activation and autoantibody production with a female sex preponderance. We quantified interactions of sex and genetic variation on the development of autoimmune B-cell phenotypes and autoantibodies in the BXD2 murine model of lupus using a cohort of backcrossed progeny (BXD2 x C57BL/6J) x BXD2. Sex was the key factor leading to increased total IgG, IgG2b, and autoantibodies. The percentage of T-bet+CD11c+ IgD+ activated naive B cells (aNAV) was higher in females and was associated with increased T-bet+CD11c+ IgD- age-related B cells, Fas+GL7+ germinal center B cells, Cxcr5-Icos+ peripheral T-helper cells, and Cxcr5+Icos+ follicular T-helper cells. IFN-ß was elevated in females. Variation in aNAV cells was mapped to Chr 7 in a locus that shows significant interactions between the female sex and heterozygous B/D variant. Our results suggest that activation of naive B cells forms the basis for the female-predominant development of autoantibodies in lupus-susceptible BXD2 mice.

Effect of Traditional Chinese Medicine combined with Western Medicine on blood lipid levels and inflammatory factors in patients with angina pectoris in coronary heart disease identified as intermingled phlegm and blood stasis syndrome: a network Meta-analysis.

OBJECTIVE: To evaluate the clinical efficacy of Traditional Chinese Medicine prescriptions for resolving phlegm in the treatment of angina pectoris of phlegm-stasis coronary heart disease by a network Meta-analysis. METHODS: Randomized controlled trials (RCTs) on clinical efficacy of CHD angina pectoris with interaction of phlegm and blood stasis were searched in PubMed, Springer, the Cochrane Library and Chinese-language databases China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data from their inception to December 2021. Literature was screened and literature bias risk was assessed by RevMan5.4 software. The overall response rate, the duration of angina attack, the levels of serum lipids such as total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C), and expression of hypersensitive C-reactive protein (hs-CRP) were selected as outcome indicators for network Meta-analysis and mapped using Stata15.1 software. RESULTS: Totally, 26 RCTs were included, involving 2098 participants. There were 6 TCM formulas with the effects of dispelling phlegm and removing blood stasis. Taking conventional Western Medicine as the common intervention measures, the results showed that the overall response improvement rate from high to low was displayed as modified Xiaoxianxiong decoction (, MXD), Danlou tablet (, DT), modified Gualou Xiebai Banxia decoction (, MGXBD), modified Wendan decoction (, MWD), modified Zhishi Xiebai Guizhi decoction (, MZXGD), and modified Erchen decoction (, MED). The sequence of angina attack duration improvement from high to low was MZXGD, MGXBD, DT, MWD, MXD. The sequence of TC improvement from high to low was MZXGD, MED, DT, and MGXBD. Sequence of improving TG from high to low was MED, MZXGD, MGXBD, and DT. For LDL-C improvement, the effect from good to poor was MZXGD, MGXBD, DT, and MED. With regard to HDL-C improvement, the effect was ranked as MED, MZXGD, MGXBD, and DT from good to poor. hs-CRP expression from high to low was MZXGD, MXD, MED, MWD, and MGXBD. CONCLUSION: TCM formula with the effects of dispelling phlegm and removing blood stasis combined with conventional Western Medicine has obvious advantages in treating CHD angina pectoris with interaction of phlegm and blood stasis. MZXGD has great potential in increasing the overall response rate, reducing Duration of angina attack improving blood lipids, and reducing inflammatory factors. However, due to the limitations of extant studies, the conclusions of this study need to be confirmed by numerous reasonably-designed RCTs.

The Oral Inactivated Porcine Epidemic Diarrhea Virus Presenting in the Intestine Induces Mucosal Immunity in Mice with Alginate-Chitosan Microcapsules.

The porcine epidemic diarrhea virus, PEDV, which causes diarrhea, vomiting and death in piglets, causes huge economic losses. Therefore, understanding how to induce mucosal immune responses in piglets is essential in the mechanism and application against PEDV infection with mucosal immunity. A method of treatment in our research was used to make an oral vaccine that packaged the inactive PEDV with microencapsulation, which consisted of sodium alginate and chitosan, and adapted the condition of the gut in mice. The in vitro release experiment of microcapsules showed that inactive PEDV was not only easily released in saline and acid solutions but also had an excellent storage tolerance, and was suitable for use as an oral vaccine. Interestingly, both experimental groups with different doses of inactive virus enhanced the secretion of specific antibodies in the serum and intestinal mucus, which caused the effective neutralization against PEDV in the Vero cell by both IgG and IgA, respectively. Moreover, the microencapsulation could stimulate the differentiation of CD11b+ and CD11c+ dendritic cells, which means that the microencapsulation was also identified as an oral adjuvant to help phagocytosis of dendritic cells in mice. Flow cytometry revealed that the B220+ and CD23+ of the B cells could significantly increase antibody production with the stimulation from the antigens' PEDV groups, and the microencapsulation could also increase the cell viability of B cells, stimulating the secretion of antibodies such as IgG and IgA in mice. In addition, the microencapsulation promoted the expression of anti-inflammatory cytokines, such as IL-10 and TGF-ß. Moreover, proinflammatory cytokines, such as IL-1, TNF-α, and IL-17, were inhibited by alginate and chitosan in the microencapsulation groups compared with the inactivated PEDV group. Taken together, our results demonstrate that the microparticle could play the role of mucosal adjuvant, and release inactivated PEDV in the gut, which can effectively stimulate mucosal and systemic immune responses in mice.

Application of enhanced recovery after surgery in partial nephrectomy for renal tumors: A systematic review and meta-analysis.

Objectives: In recent years, enhanced recovery after surgery (ERAS) has been widely used in the field of urology, especially in radical cystectomy and radical prostatectomy, and has demonstrated its advantages. Although studies on the application of ERAS in partial nephrectomy for renal tumors are increasing, the conclusions are mixed, especially in terms of postoperative complications, etc, and its safety and efficacy are questionable. We conducted a systematic review and meta-analysis to assess the safety and efficacy of ERAS in the application of partial nephrectomy for renal tumors. Methods: Pubmed, Embase, Cohrance library, Web of science and Chinese databases (CNKI, VIP, Wangfang and CBM) were systematically searched for all published literature related to the application of enhanced recovery after surgery in partial nephrectomy for renal tumors from the date of establishment to July 15, 2022, and the literature was screened by inclusion/exclusion criteria. The quality of the literature was evaluated for each of the included literature. This Meta-analysis was registered on PROSPERO (CRD42022351038) and data were processed using Review Manager 5.4 and Stata 16.0SE. The results were presented and analyzed by weighted mean difference (WMD), Standard Mean Difference (SMD) and risk ratio (RR) at their 95% confidence interval (CI). Finally, the limitations of this study are analyzed in order to provide a more objective view of the results of this study. Results: This meta-analysis included 35 literature, including 19 retrospective cohort studies and 16 randomized controlled studies with a total of 3171 patients. The ERAS group was found to exhibit advantages in the following outcome indicators: postoperative hospital stay (WMD=-2.88, 95% CI: -3.71 to -2.05, p<0.001), total hospital stay (WMD=-3.35, 95% CI: -3.73 to -2.97, p<0.001), time to first postoperative bed activity (SMD=-3.80, 95% CI: -4.61 to -2.98, p < 0.001), time to first postoperative anal exhaust (SMD=-1.55, 95% CI: -1.92 to -1.18, p < 0.001), time to first postoperative bowel movement (SMD=-1.52, 95% CI: -2.08 to -0.96, p < 0.001), time to first postoperative food intake (SMD=-3.65, 95% CI: -4.59 to -2.71, p<0.001), time to catheter removal (SMD=-3.69, 95% CI: -4.61 to -2.77, p<0.001), time to drainage tube removal (SMD=-2.77, 95% CI: -3.41 to -2.13, p<0.001), total postoperative complication incidence (RR=0.41, 95% CI: 0.35 to 0.49, p<0.001), postoperative hemorrhage incidence (RR=0.41, 95% CI: 0.26 to 0.66, p<0.001), postoperative urinary leakage incidence (RR=0.27, 95% CI: 0.11 to 0.65, p=0.004), deep vein thrombosis incidence (RR=0.14, 95% CI: 0.06 to 0.36, p<0.001), and hospitalization costs (WMD=-0.82, 95% CI: -1.20 to -0.43, p<0.001). Conclusion: ERAS is safe and effective in partial nephrectomy of renal tumors. In addition, ERAS can improve the turnover rate of hospital beds, reduce medical costs and improve the utilization rate of medical resources. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022351038.

Difference analysis of Doppler ultrasound blood flow of Cunkou (radial artery) pulse, Renying (carotid artery) pulse, and Fuyang (anterior tibial artery) pulse.

OBJECTIVE: To analyze the Doppler ultrasound blood flow of Renying (carotid artery) pulse, Cunkou (radial artery) pulse, and Fuyang (anterior tibial artery) pulse in the normal group and the functional constipation with gastrointestinal heat (FCGH) group, and to compare and explore the differences of Renying, Cunkou and Fuyang pulses. METHODS: Sixty normal subjects and 60 patients with gastrointestinal heat constipation were collected in the department of ultrasound, Beijing Anzhen Hospital, Capital Medical University. Doppler ultrasound was used to observe the blood flow indexes including maximum systolic velocity (Vp), maximum diastolic velocity (Vd), mean velocity (Vm), pulse index (PI), resistance index (RI), vascular diameter (D), and circulation blood flow cycle (ET) of Renying pulse, Cunkou pulse and Fuyang pulse in the normal group and patients with gastrointestinal heat constipation. The differences of these three pulses were compared between the normal group and the FCGH group. RESULTS: The PI, Vp, Vm, RI, and D of the three pulses in the normal group were statistically significant different ( < 0.01). In the comparison of Doppler flow diagram of three pulses in the FCGH group, there were significant differences in PI, Vd, Vp, Vm, RI, and D ( < 0.01). CONCLUSION: Under normal conditions, the indexes of Renying pulse Doppler flow diagram, Cunkou pulse Doppler flow diagram, and Fuyang pulse Doppler flow diagram are significantly different. In the FCGH group, most of the indexes of Renying pulse Doppler flow diagram, Cunkou pulse Doppler flow diagram, and Fuyang pulse Doppler flow diagram are different. This result verified the necessity of simultaneous examinations of all Renying, Cunkou, and Fuyang pulses in modern Chinese medicine.

Osteoblasts Regulate the Expression of ADAMTS and MMPs in Chondrocytes through ERK Signaling Pathway.

OBJECTIVE: Degradative enzymes such as matrix metalloproteinase (MMP) and disintegrin metalloproteinase with platelet thrombin-sensitive protein-like motifs (ADAMTS) play a key role in the development of osteoarthritis (OA). We aimed to investigate the effects of OA subchondral osteoblasts on the expression of ADAMTS4, ADAMTS5, MMP-3, MMP-9, and MMP-13 in chondrocytes and the regulation of mitogen-activated protein kinase (MAPK) signaling pathway. METHODS: A rat knee OA model was constructed by cutting the anterior cruciate ligament of the knee joints, and normal rat articular cartilage chondrocytes (N-ACC), OA rat articular cartilage chondrocytes (O-ACC), normal subchondral bone osteoblasts (N-SBO), and OA subchondral bone osteoblasts (O-SBO) were isolated and extracted. The expressions of O-ACC and O-SBO COL1 and COL2 were detected respectively. Chondrocytes were identified by immunofluorescence of COL2 and toluidine blue staining, and osteoblasts were identified by COL1 immunofluorescence, alkaline phosphatase (ALP), and Alizarin Red staining. Gene expression of COL1, COL2, and aggrecan in normal chondrocytes and OA chondrocytes, and gene expression of osteoblast ALP and osteocalcin (OCN) were detected by RT-PCR to identify the two chondrocytes and the two osteoblast phenotypes. The constructing N-ACC group, O-ACC group, N-ACC + N-SBO group, N-ACC + O-SBO group, O-ACC + N-SBO group, O-ACC + O-SBO group, I + N-ACC + O-SBO group, and I + O-ACC + O-SBO group cell cultures, and the expression of ERK, ADAMTS4, ADAMTS5, MMP-3, MMP-9, and MMP-13 genes in chondrocytes cultured for 0, 24, 48, and 72 h were detected by RT-PCR. The protein expressions of pERK, ADAMTS4, ADAMTS5, MMP-3, MMP-9, and MMP-13 were detected by Western blot. RESULTS: · The X-ray showed that the knee joint space of the affected limb became narrow.. · The results of RT-PCR of COL2 and aggrecan gene in OA and normal chondrocytes suggest that the relative expression of COL2 in OA articular chondrocytes (0.24 ± 0.07) is significantly lower than that in normal cartilage (0.61 ± 0.07) (p < 0.05). The relative expression of AGG (0.37 ± 0.16) in OA chondrocytes was significantly lower than that of normal chondrocytes AGG (1.30 ± 0.25) (p < 0.05). The expression of COL1 was very low, and was not statistically significant.. · The results of RT-PCR of the osteoblast ALP and OCN gene indicated that gene expression of ALP (12.30 ± 1.17) and OCN (20.47 ± 4.19)was upregulated when compared with the relative expression of ALP (4.66 ± 0.71) (p < 0.05) and OCN (12.17 ± 2.76) (p < 0.05) in normal osteoblasts, indicating that osteoblasts of OA have greater osteogenic potential than normal osteoblasts.. · The expressions of ADAMTS4, ADAMTS5, MMP-3, MMP-9, and MMP-13 genes and proteins in OA chondrocytes or normal chondrocytes were basically unchanged when they were cocultured with normal osteoblasts. Indirect coculture of OA osteoblasts and chondrocytes could promote the expression of ADAMTS4, ADAMTS5, MMP-3, MMP-9, and MMP-13 genes and proteins in chondrocytes. Overexpression of ADAMTS and MMP in coculture systems can be reversed by MAPK-ERK inhibitors.. CONCLUSIONS: · OA subchondral bone osteoblasts can promote the overexpression of ADAMTS and MMPs in chondrocytes.. · The ERK signaling pathway may be involved in the regulation of the effect of subchondral bone osteoblasts on chondrocytes..

Effect of preoperative TACE on the complications after hepatectomy for hepatocellular carcinoma: a propensity score matching analysis / 中华肝胆外科杂志

Objective:To study the effect of preoperative transcatheter arterial chemoembolization (TACE) on postoperative complications after hepatectomy in patients with hepatocellular carcinoma (HCC) by propensity score matching analysis.Methods:Of 1 666 patients with HCC undergoing hepatectomy in Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology and Tianyou Hospital of Wuhan University of Science and Technology from March 2015 to March 2021 were retrospectively screened. Of 262 patients were enrolled, including 236 males and 26 females, aged (50.3±11.8) years. Of 131 patients were enrolled in both the single surgery group and the combined group (preoperative TACE + surgical resection). Factors affecting the complications after hepatectomy in patients with HCC were analyzed using univariate and multivariate logistic regression method.Results:After matching the propensity score, the incidence of postoperative complications in the single surgery group was 22.1% (29/131), lower than that in the combined group [41.2% (54/131), χ 2=11.02, P<0.001]. The incidence of bile leakage in the single surgery group [2.3% (3/131)] was also lower than that in the combined group [(9.2% (12/131), χ 2=5.73, P=0.017]. Multivariate logistic regression analysis showed that the combined group ( OR=2.43, 95% CI: 1.28-4.61, P=0.007) had an increased incidence of postoperative complications, so did patients with a preoperative alpha-fetoprotein > 400 μg/L, anatomic hepatectomy, long operation time, and hilar occlusion. Conclusion:Preoperative TACE could be a risk factor for postoperative complications in patients with HCC, especially for the postoperative biliary leakage.

Application of laparoscopic radical cholecystectomy in the treatment of stage Ⅲ gallbladder cancer / 中华肝胆外科杂志

Objective:To study the clinical efficacy of laparoscopic radical cholecystectomy in the treatment of stage Ⅲ gallbladder cancer.Methods:The clinical characteristics and postoperative follow-up data of 184 patients (male 66, and female 118) who underwent radical cholecystectomy for stage Ⅲ gallbladder cancer at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from May 2015 to May 2022, were retrospectively analyzed. The age was (67.0±8.6) years old (range 38 to 85 years old). There were 71 patients in the laparoscopic group and 113 in the open group. The general medical data, surgery-related indicators and complications were analyzed. Follow-up was completed by outpatient visits and by telephone.Results:The laparoscopic group showed better postoperative alanine aminotransferase [67.5 (40.0, 138.5) vs. 104.0 (45.0, 252.2) U/L] and aspartate aminotransferase [41.5 (26.0, 71.2) vs. 53.0 (30.2, 153.5) U/L] recovery, higher albumin levels [32.05 (30.18, 35.20) vs. 30.50 (27.70, 33.50) g/L], earlier abdominal drainage tube removal [8.00(6.00, 10.25) vs. 10.00(6.00, 13.00)d], shorter hospital stay [10.00(8.00, 15.25) vs. 14.00(9.00, 19.00) d] and lower incidences of complications [(14.1%(10/71) vs. 31.9%(36/113)] when compared with the open group (all P<0.05). The 1 year (49.1% vs 61.0%), 2 years (24.0% vs. 28.5%), 3 years (16.0% vs. 14.5%) overall survival ( P=0.640), and the 3 years progression-free survival (18.3% vs. 15.0%, P=0.463) showed no significant difference between the 2 groups. Conclusion:Laparoscopic surgery for AJCC TNM stage Ⅲ gallbladder cancer showed comparable results with open surgery. When compared with open surgery, laparoscopic radical resection of gallbladder cancer had the advantages of earlier removal of abdominal drainage tube, lower incidence of postoperative complications, and shorter hospital stay.

Effects of educational level on the choice of intervention strategies for smoking cessation in patients with moderate to severe tobacco dependence / 中国基层医药

Objective:To investigate the effects of educational level on smoking cessation in patients with moderate to severe tobacco dependence, explore effective individualized smoking cessation methods, and increase smoking cessation rate.Methods:A total of 480 patients with moderate to severe tobacco dependence who were willing to quit smoking and received treatment in the Department of Respiratory and Critical Care Medicine, Shengli Oilfield Central Hospital from January to December 2020 were included in this study. They were divided into four groups ( n = 120/group) according to their educational level: group A (elementary school and below), group B (junior high school and senior high school), group C (technical secondary school or college), and group D (university and above). All patients were randomly assigned to undergo "5A" intervention alone or "5A" intervention combined with varenicline intervention (combined intervention). Patients' awareness of the health risks of tobacco smoking was compared among the four groups. The smoking cessation rate measured at different time points was compared between different intervention strategies. Results:The scores of health risk of tobacco smoking in groups D, C, B, and A were (806.5 ± 35.7) points, (710.8 ± 26.2) points, (643.6 ± 43.4) points, and (512.4 ± 30.1) points, respectively. Patients with high education levels had high awareness of the health risk of tobacco smoking ( F = 1 543.26, P < 0.001). At 1, 3, and 6 months, the smoking cessation rate of combined intervention was higher than that of "5A" intervention alone in each group (group A: χ2 = 3.85, 4.23, 4.10, group B: χ2 = 4.30, 4.09, 4.60, group C: χ2 = 6.81, 4.30, 4.03, group D: χ2 = 6.71, 6.51, 4.73, all P < 0.05). The smoking cessation rate after 6 months of "5A" intervention alone or combined intervention in group D was 60.0% and 78.3% respectively, which were significantly higher than 41.7% and 60.0% in group C, 23.3% and 41.7% in group B, and 20.0% and 36.7% in group A ( χ2 = 26.59, 26.12, both P < 0.001). At different time points, the smoking cessation rates of the "5A" intervention alone in group D were significantly higher than those of combined intervention in groups A and B ( χ2 = 9.25, 25.04, 7.29, all P < 0.05). Conclusion:Awareness of the health risks of tobacco smoking is related to a patient's educational level, and affects smoking cessation. Individualized smoking cessation interventions based on a patient's educational level can increase the rate of smoking cessation.

Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection / 药物分析学报

On December 22,2021,the United States Food and Drug Administration approved the first main protease inhibitor,i.e.,oral antiviral nirmatrelvir(PF-07321332)/ritonavir(Paxlovid),for the treatment of early severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Nirmatrelvir inhibits SARS-CoV-2 infection,but high doses or long-term treatment may cause embryonic developmental toxicity and changes in host gene expression.The chiral structure of nirmatrelvir plays a key role in its antiviral activity.Ritonavir boosts the efficacy of nirmatrelvir by inactivating cytochrome P450 3A4 expression and occupying the plasma protein binding sites.Multidrug resistance protein 1 inhibitors may increase the efficacy of nirmatrelvir.However,Paxlovid has many contraindications.Some patients treated with Paxlovid experience a second round of coronavirus disease 2019(COVID-19)symptoms soon after re-covery.Interestingly,the antiviral activity of nirmatrelvir metabolites,such as compounds 12-18,is similar to or higher than that of nirmatrelvir.Herein,we review the advances and challenges in using nirmatrelvir and its derivatives with the aim of providing knowledge for drug developers and physicians in the fight against COVID-19.

Serum B7 homologous protein 2, tumor necrosis factor-related apoptosis-inducing ligand, interleukin-37, interleukin-17A levels in patients with primary immune thrombocytopenia and their clinical significance / 中国医师进修杂志

Objective:To explore the changes of serum B7 homolog 2 (B7-H2), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interleukin(IL)-37 and IL-17A levels in patients with primary immune thrombocytopenia (ITP), and to analyze the clinical guiding significance of each index level in the diagnosis and treatment of ITP.Methods:A total of 90 patients with ITP treated in Jining Hospital of Traditional Chinese Medicine from September 2018 to September 2020 were retrospectively selected as the research group, and 90 healthy patients during the same period were selected as the normal control group. The levels of serum B7-H2, TRAIL, IL-37, IL-17A and platelet count (PLT) in the two groups were compared, and the clinical guidance significance of each index level in the diagnosis and treatment of ITP were analyzed by receiver operating characteristic(ROC) curve.Results:The serum levels of B7-H2, TRAIL, IL-37 and IL-17A in the research group were higher than those in the normal control group, and PLT was lower than that in the normal control group: (25.12 ± 4.29) μg/L vs. (12.26 ± 3.10) μg/L, (0.92 ± 0.20) μg/L vs.(0.46 ± 0.13) μg/L, (145.02 ± 43.18) ng/L vs. (50.23 ± 14.07) ng/L, (21.63 ± 5.06) ng/L vs. (7.71 ± 2.04) ng/L, (16.12 ± 4.61) × 10 9/L vs. (200.86 ± 61.4) × 10 9/L, there were statistical differences ( P<0.05). After treatment for 3 months, 73 patients obtained remission, and 13 patients were non-remission. The levels of B7-H2, TRAIL, IL-37, IL-17A in the non-remission group before and after treatment were higher than those in the remission group, and PLT was lower than that in the remission group, there were statistical differences ( P<0.05). Pearson correlation analysis showed that the levels of serum B7-H2, TRAIL, IL-37 and IL-17A were negatively correlated with PLT ( P<0.05). The ROC curve analysis showed that the area under the curve of serum B7-H2, TRAIL, IL-37 and IL-17A in prognostic prediction was 0.916, the sensitivity and the specificity were 94.12% and 86.30%. Conclusions:The serum levels of B7-H2, TRAIL, IL-37 and IL-17A in patients with ITP are significantly elevated, and are closely related to the level of PLT. Combined detection can help clinically predict the direction of disease outcome.

Effects of electroacupuncture preconditioning of "Neiguan"(PC 6) on myocardial ischemia reperfusion injury via Akt/mTOR pathway / 国际中医中药杂志

Objective:To observe the effects of electroacupuncture preconditioning on the autophagy-related pathway protein kinase B (Akt)/mammalian target of rapamycin (mTOR) in myocardial tissue of rats with myocardial ischemia reperfusion injury (MIRI); To investigate the protective mechanism of "Neiguan"(PC 6) on myocardial injury.Methods:Totally 48 SD rats were randomly divided into blank group, sham-operation group, model group and Neiguan group ( n=12 in each group). The Neiguan group was applied to bilateral "Neiguan"(PC 6) by electroacupuncture for 30 min, once daily for consecutive 7 days before model replication. Except in the blank group, the MIRI model was established by ligation of the descending anterior branch of the left coronary artery in the rest groups after the intervention. The histomorphological changes in the myocardium of the rats were observed by HE staining, and the expression levels of Akt, phosphorylated Akt (p-Akt), mTOR and phosphorylated mTOR (p-mTOR) in the myocardium were measured by protein immunoblotting. The ratio of p-Akt/Akt and p-mTOR/mTOR was calculated. Results:In the blank group, the myocardial fibres were arranged regularly and neatly, and no inflammatory cell infiltration or haemorrhage was seen in the interstitium; in the sham-operation group, the arrangement of myocardial fibers was slightly irregular, no rupture was found, and a small amount of myocardial fiber gap was slightly enlarged; in the model group, the distribution of myocardial fibers was disordered, hypertrophic cardiomyocytes increased, some mitochondria were red and swollen or the outer membrane was ruptured, and inflammatory infiltration and hemorrhage were seen in the interstitium; the extent of myocardial lesions in the Neiguan group was less than that in the model group, with a small amount of interstitial hemorrhage and inflammatory cell infiltration. There was no statistical significance in the levels of Akt and mTOR in the myocardial tissues of the rats in each group ( P>0.05); compared with the sham-operation group, the levels of p-Akt, p-mTOR and p-Akt/Akt, p-mTOR/mTOR in the model group decreased ( P<0.01); compared with the model group, the levels of p-Akt, p-mTOR and p-Akt/Akt, p-mTOR/mTOR in the Neiguan group increased ( P<0.01). Conclusion:Electroacupuncture preconditioning may inhibit excessive autophagy by activating the Akt/mTOR pathway in cardiomyocytes of MIRI rats, thereby exerting a protective effect on the myocardium.

Research progress on factors influencing the success rate of ureteral access sheath / 国际外科学杂志

During the operation of flexible ureteroscope, the ureteral access sheath is effectively placed, which accelerates the circulation of fluid in the kidney, thus reducing the pressure in the kidney and enhancing the clarity of the operation field. The success rate of lithotripsy and the risk of postoperative infection depend on the position of the ureteral access sheath. This article reviews the factors affecting the insertion process of the ureteral access sheath and the methods to improve the success rate of the insertion of the ureteral access sheath.

Application progress of artificial intelligence in the screening and identification of drug targets / 中国药科大学学报

@#In recent years, artificial intelligence (AI) has developed rapidly, with improved computing power and algorithms, which has greatly facilitated the collection and processing of biological, chemical information and clinical data, injecting new vitality into the research and development of new drugs.In this review, we began with a brief overview of the development and the main algorithms of AI in drug discovery.Then we elaborated through several specific cases on the various scenarios of AI application, including target identification, protein structure prediction, hit generation and optimization etc.Finally, we focused on a recent example to discuss the high efficiency of "end-to-end" application of AI.

Intervention effect of Qufeng Gutong Cataplasm on myofascial pain syndrome in rats and its mechanism / 中国中药杂志

This paper aims to investigate the intervention effect of Qufeng Gutong Cataplasm(QFGT) on myofascial pain syndrome(MPS) in rats and to preliminarily explain its mechanism from the perspective of improving muscle inflammation and pain. Male SD rats were divided into 6 groups, namely normal group, model group, positive control drug(Huoxue Zhitong Ointment, HXZT) group, and low, medium, and high-dose QFGT groups(75, 150, and 300 mg·d~(-1)). The rat model of MPS was established by striking combined with centrifugation for 8 weeks, during which QFGT and HXZT were used for corresponding intervention. Standard VonFrey fiber was used to evaluate the mechanical pain threshold, and acetone was used to detect the cold pain threshold. The electrophysiological activity of muscle at trigger point was detected, and the electromuscular analysis of trigger point was performed. CatWalk gait analyzer was used to detect pain-induced gait adaptation changes. The hematoxylin-eosin(HE) staining was used to observe the pathological changes in muscle and skin tissues at the trigger point of rats. Immunohistochemistry was used to detect the expression of capsaicin receptor transient receptor potential vanilloid 1(TRPV1) in muscle tissues and interleukin(IL)-33 in skin tissues at the trigger point. The protein expression levels of TRPV1, protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), IL-1β, and tumor necrosis factor-α(TNF-α) in muscle tissues at the trigger point were detected by Western blot. The results showed that as compared with the model group, the mechanical pain threshold and cold pain threshold of rats in other groups were increased after treatment with QFGT. The spontaneous electromyography(EMG) activity was observed in the model group, but QFGT alleviated the EMG activity in a dose-dependent manner. Gait analysis showed that standing duration, average intensity, swing speed, maximum contact point, maximum contact area, paw print length, paw print width, and paw print area were significantly improved in all QFGT groups. Pathological results showed that the disorder of muscle arrangement at the trigger point was decreased, muscle fiber adhesion and atrophy were reduced, and inflammatory cell infiltration was alleviated after treatment with QFGT. In addition, QFGT and HXZT both inhibited the protein expression of TRPV1, PI3K, Akt, p-Akt, IL-1β, and TNF-α in the muscle tissues of rats with MPS. However, there was no significant difference in the pathological structure and expression of IL-33 in the treated skin as compared with the normal group. The related results have proved that QFGT can inhibit the release of inflammatory factors by inhibiting the TRPV1/PI3K/Akt signaling pathway in the muscle trigger point of rats with MPS and finally attenuate the atrophy and adhesion of local muscles and inflammatory infiltration, thereby relieving the muscle pain of rats with MPS, and local administration has no skin irritation.

Identification of core pathogenic genes and pathways in elderly osteoporosis based on bioinformatics analysis / 中华预防医学杂志

Objective: Using bioinformatics methods to analyze the core pathogenic genes and related pathways in elderly osteoporosis. Methods: From November 2020 and August 2021, eight elderly osteoporosis patients who received treatment and five healthy participants who underwent physical examinations in Beijing Jishuitan Hospital were selected as subjects. The expression level of RNA in the peripheral blood of eight elderly osteoporosis patients and five healthy participants was collected for high-throughput transcriptome sequencing and analysis. The gene ontology (GO) analysis Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed for the differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was constructed using the STRING website and Cytoscape software, and the most significant modules and hub genes were screened out. Results: Among the eight elderly osteoporosis patients, there were seven females and one male, with an average age of 72.4 years (SD=4.2). Among the five healthy participants, there were four females and one male, with an average age of 68.2 years (SD=5.7). A total of 1 635 DEGs (847 up-regulated and 788 down-regulated) were identified. GO analysis revealed that the molecular functions of DEGs were mainly enriched in structural constituents of the ribosome, protein dimerization activity, and cellular components were mainly enriched in the nucleosome, DNA packaging complex, cytosolic part, protein-DNA complex and the cytosolic ribosome. KEGG pathway analysis showed that DEGs were mainly enriched in systemic lupus erythematosus and ribosome. Gene UBA52, UBB, RPS27A, RPS15, RPS12, RPL13A, RPL23A, RPL10A, RPS25 and RPS6 were selected and seven of them could encode ribosome proteins. Conclusion: The pathogenesis of elderly osteoporosis may be associated with ribosome-related genes and pathways.

Developmental effects of TCIPP and TnBP on zebrafish (Danio rerio) embryos / 中华预防医学杂志

Objective: To investigate the toxicity of tris (2-chloropropyl) phosphate (TCIPP) and tributyl phosphate (TnBP) on the growth and development of zebrafish embryos, as well as to explore the underlying mechanisms at the transcriptional level. Methods: With zebrafish as a model, two hpf zebrafish embryos were exposed to TCIPP and TnBP (0.1, 1, 10, 100, 500, and 1 000 μmol/L) using the semi-static method, and their rates of lethality and hatchability were determined. The transcriptome changes of 120 hpf juvenile zebrafish exposed to environmentally relevant concentrations of 0.1 and 1 μmol/L were measured. Results: The 50% lethal concentrations (LC50) of TCIPP and TnBP for zebrafish embryos were 155.30 and 27.62 μmol/L (96 hpf), 156.5 and 26.05 μmol/L (120 hpf), respectively. The 72 hpf hatching rates of TCIPP (100 μmol/L) and TnBP (10 μmol/L) were (23.33±7.72)% and (91.67±2.97)%, which were significantly decreased compared with the control group (P<0.05). Transcriptome analysis showed that TnBP had more differential genes (DEGs) than TCIPP, with a dose-response relationship. These DEGs were enriched in 32 pathways in total, including those involved in oxidative stress, energy metabolism, lipid metabolism, and nuclear receptor-related pathways, using the IPA pathway analysis. Among them, three enriched pathways overlapped between TCIPP and TnBP, including TR/RXR activation and CAR/RXR activation. Additionally, DEGs were also mapped onto pathways of LXR/RXR activation and oxidative stress for TnBP exposure only. Conclusion: Both TCIPP and TnBP have growth and developmental toxicities in zebrafish embryos, with distinct biomolecular mechanisms, and TnBP has a stronger effect than TCIPP.