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..

Predictive value of peripheral blood lymphocyte subsets for children with intravenous immunoglobulin-resistant Kawasaki disease / 中国当代儿科杂志

OBJECTIVES@#Based on peripheral blood lymphocyte subsets and common laboratory test indexes, this study aimed to construct a predictive scoring system for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD).@*METHODS@#Children hospitalized in Tianjin Children's Hospital from January 2021 to March 2023 were included in the study (185 cases of IVIG-sensitive KD and 41 cases of IVIG -resistant KD). Forty-six healthy children matched for age and gender were selected as controls. The relative percentage and absolute counts of peripheral lymphocyte subsets were measured by flow cytometry. Multivariate logistic regression was used to identify the predictive factors for IVIG-resistant KD and to construct a predictive scoring system for predicting IVIG-resistant KD.@*RESULTS@#The multivariate logistic regression analysis showed that CD4+ T cell absolute count, natural killer cell absolute count, serum sodium level, globulin level, and total bilirubin level were identified as predictive factors for IVIG-resistant KD (P<0.05). The predictive scoring system based on these factors achieved a sensitivity of 70.7% and a specificity of 83.8% in predicting IVIG-resistant KD.@*CONCLUSIONS@#Peripheral blood lymphocyte subsets can serve as predictive indicators for IVIG-resistant KD in children. The introduction of this indicator and the establishment of a scoring system based on it can provide a higher accuracy in predicting IVIG-resistant KD in children.

Baimai Ointment relieves chronic pain induced by chronic compression of dorsal root ganglion in rats by regulating neuroactive ligand-receptor interaction and HIF-1 signaling pathway / 中国中药杂志

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.

Effect of physical activity on executive function of children and adolescents: a systematic review / 中国康复理论与实践

ObjectiveTo analyze the effect of physical activity on executive function of children and adolescents, and sort out the related factors. MethodsArticles about physical activity intervention for children and adolescents on executive function were retrieved from CNKI, Wanfang Data, Google Scholar, Wiley Online Library and PubMed, from January 1st, 2010 to June 30th, 2021. The articles were screened, evaluated and systematically reviewed. ResultsA total of 21 articles were included, from eleven countries, including 13 randomized controlled trials, involving 2 496 subjects, aged five to 18 years. The articles were published from 2010 to 2019, with mean score of Physiotherapy Evidence Database scale as 5.57. The physical activity intervention mainly involved physical fitness, skills and sport games, with low to high intensity, eight to 120 minutes a time, one to five times a week, no more than ten months. Physical activity was indicated to improve the executive function, specifically inhibition control, working memory and cognitive flexibility, such as the improvement of the accuracy and reaction time of cognitive tasks, and activation of bilateral prefrontal cortex activity. Types, intensity, duration, frequency and cycle of physical activity, participant selection, and assessment tools were related to the effect of intervention. ConclusionPhysical activity can improve the inhibition control, working memory and cognitive flexibility of children and adolescents. The main factors related to the intervention effect are the physical activity elements, the participant's factors and the experimental design factors.

Clinical characteristics of children infected with SARS-CoV-2 Omicron variant combined with allergic disease / 中华儿科杂志

Objective: To investigate the clinical characteristics of children with allergic diseases suffering from SARS-CoV-2 Omicron variant strains. Methods: This was a cross-sectional study. A total of 43 pediatric patients with allergic diseases infected by SARS-CoV-2 from April 25, 2022 to June 8, 2022 in Shanghai Jiao Tong University School of Medicine were selected as the allergic disease group, while 114 cases without underlying diseases and 16 cases with other underlying diseases were selected as control groups diagnosed at the same period. Clinical data including clinical features, laboratory tests, duration of hospitalization, and the time to negative turn of novel coronavirus nucleic acid were collected and analysed. Kruskal-Wallis H test, chi-square test or Fisher exact test were used for comparison among three groups. Results: Among the 43 patients with allergic diseases, 28 were males and 15 were females, with an age of 4.4 (2.1, 8.2) years on admission, including 32 mild cases and 11 common cases. The allergic disease group included 20 cases (46.5%) of atopic dermatitis and eczema, followed by 14 cases (32.6%) of rhinitis, 8 cases (18.6%) of food allergies, 7 cases (16.3%) of asthma, 4 cases (9.3%) of allergic conjunctivitis and 2 cases (4.7%) of drug allergy. Among the 114 cases without underlying diseases, 57 were males and 57 were females, with an age of 2.8 (1.2, 5.6) years on admission, including 93 mild cases and 21 common cases. Among the 16 cases with other underlying diseases, 9 were males and 7 were females, with an age of 3.0 (2.6, 10.8) years on admission, including 13 cases mild and 3 cases common cases. Children with allergic diseases had higher frequency of sore throat and vomiting than those without underlying diseases (10 cases (23.3%) vs.9 cases (7.9%), 14 cases (32.6%) vs. 11 cases (9.6%), χ²=6.93, 12.24, both P<0.05). The lymphocyte count of patients with allergic disease was lower than those without underlying disease (1.1 (0.7,1.7)×109 vs. 1.6 (1.1,2.7)×109/L, H=-28.00,P=0.005). There were no significant differences in age, gender, typing of SARS-CoV-2, the duration of hospitalization, cycle threshold values of SARS-CoV-2 and the time to negative turn of novel coronavirus nucleic acid among the three groups (all P>0.05). Conclusions: Children with allergic diseases may suffer from sore throat and vomiting more frequently when infected with SARS-CoV-2 Omicron variant. The combination of allergic diseases hardly influenced the disease course of SARS-CoV-2 in children.

The expression and function of PD-L1 in CD133(+) human liver cancer stem-like cells / 中华肿瘤杂志

Objective: To investigate the expression of programmed death protein-ligand 1 (PD-L1) in liver cancer stem-like cells (LCSLC) and its effect on the characteristics of tumor stem cells and tumor biological function, to explore the upstream signaling pathway regulating PD-L1 expression in LCSLC and the downstream molecular mechanism of PD-L1 regulating stem cell characteristics, also tumor biological functions. Methods: HepG2 was cultured by sphere-formating method to obtain LCSLC. The expressions of CD133 and other stemness markers were detected by flow cytometry, western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of stemness markers and PD-L1. The biological functions of the LCSLC were tested by cell function assays, to confirm that the LCSLC has the characteristics of tumor stem cells. LCSLC was treated with cell signaling pathway inhibitors to identify relevant upstream signaling pathways mediating PD-L1 expression changes. The expression of PD-L1 in LCSLC was down regulated by small interfering RNA (siRNA), the expression of stem cell markers, tumor biological functions of LCSLC, and the changes of cell signaling pathways were detected. Results: Compared with HepG2 cells, the expression rate of CD133 in LCSLC was upregulated [(92.78±6.91)% and (1.40±1.77)%, P<0.001], the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were also higher than those in HepG2 cells (P<0.05), the number of sphere-formating cells increased on day 7 [(395.30±54.05) and (124.70±19.30), P=0.001], cell migration rate increased [(35.41±6.78)% and (10.89±4.34)%, P=0.006], the number of transmembrane cells increased [(75.77±10.85) and (20.00±7.94), P=0.002], the number of cloned cells increased [(120.00±29.51) and (62.67±16.77), P=0.043]. Cell cycle experiments showed that LCSLC had significantly more cells in the G(0)/G(1) phase than those in HepG2 [(54.89±3.27) and (32.36±1.50), P<0.001]. The tumor formation experiment of mice showed that the weight of transplanted tumor in LCSLC group was (1.32±0.17)g, the volume is (1 779.0±200.2) mm(3), were higher than those of HepG2 cell [(0.31±0.06)g and (645.6±154.9)mm(3), P<0.001]. The expression level of PD-L1 protein in LCSLC was 1.88±0.52 and mRNA expression level was 2.53±0.62, both of which were higher than those of HepG2 cells (P<0.05). The expression levels of phosphorylation signal transduction and transcription activation factor 3 (p-STAT3) and p-Akt in LCSLC were higher than those in HepG2 cells (P<0.05). After the expression of p-STAT3 and p-Akt was down-regulated by inhibitor treatment, the expression of PD-L1 was also down-regulated (P<0.05). In contrast, the expression level of phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in LCSLC was lower than that in HepG2 cells (P<0.01), there was no significant change in PD-L1 expression after down-regulated by inhibitor treatment (P>0.05). After the expression of PD-L1 was knockdown by siRNA, the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were decreased compared with those of siRNA-negative control (NC) group (P<0.05). The number of sphere-formating cells decreased [(45.33±12.01) and (282.00±29.21), P<0.001], the cell migration rate was lower than that in siRNA-NC group [(20.86±2.74)% and (46.73±15.43)%, P=0.046], the number of transmembrane cells decreased [(39.67±1.53) and (102.70±11.59), P=0.001], the number of cloned cells decreased [(57.67±14.57) and (120.70±15.04), P=0.007], the number of cells in G(0)/G(1) phase decreased [(37.68±2.51) and (57.27±0.92), P<0.001], the number of cells in S phase was more than that in siRNA-NC group [(30.78±0.52) and (15.52±0.83), P<0.001]. Tumor formation in mice showed that the tumor weight of shRNA-PD-L1 group was (0.47±0.12)g, the volume is (761.3±221.4)mm(3), were lower than those of shRNA-NC group [(1.57±0.45)g and (1 829.0±218.3)mm(3), P<0.001]. Meanwhile, the expression levels of p-STAT3 and p-Akt in siRNA-PD-L1 group were decreased (P<0.05), while the expression levels of p-ERK1/2 and β-catenin did not change significantly (P>0.05). Conclusion: Elevated PD-L1 expression in CD133(+) LCSLC is crucial to maintain stemness and promotes the tumor biological function of LCSLC.

Correlation Between Vimentin and Hepatocellular Carcinoma and Intervention Effect of Jianpi Yiqi Prescription / 中国实验方剂学杂志

ObjectiveTo study the correlation between Vimentin and hepatocellular carcinoma （HCC） and the mechanism of Jianpi Yiqi prescription against HCC through Vimentin. MethodCorrelation between Vimentin and HCC was analyzed based on the cancer genome atlas（TCGA）， clinical proteomic tumor analysis consortium（CPTAC）， STRING， and Cytoscape. SD rats were randomized into normal group （normal saline， ig， once/day， 4 weeks）， model group （normal saline， ig， once/day， 4 weeks）， low-dose， medium-dose， and high-dose （5.25， 10.5， 21 g·kg-1， ig， once/day， 4 weeks） JianpiYiqi prescription groups， signal transducer and activator of transcription 3 （STAT3） inhibition group （C188-9， 4.5 mg·kg-1， ip， once/day， 4 weeks）， and glycoprotein 130 （gp130） inhibition group （SC144， 4.5 mg·kg-1， ip， once/day， 4 weeks）， 10 rats in each group. Diethylnitrosamine （DEN， 70 mg·kg-1 body weight， ip） was injected in rats except the normal group to induce HCC. After the modeling， administration began. After last administration， Real-time polymerase chain reaction（Real-time PCR） was performed to determine Vimentin mRNA level in rat liver tissue. Caspase-3 activity in liver tissue was detected by colorimetry， and expression of Rho kinase （ROCK）1， ROCK2， aurora kinase B （AURKB）， Zinc-finger protein 148 （ZNF148）/zinc-binding protein-89 （ZBP-89）， STAT3， p-STAT3， total Vimentin， and phosphorylated （p）-Vimentin in liver tissue and Vimentin in liver tissue nucleus detected by Western blot. Serum Vimentin concentration was measured by enzyme-linked immunosorbent assay （ELISA）. ResultVimentin mRNA level was high in tissues from HCC patients with different cancer stages （stage Ⅰ-Ⅳ）， different pathological grades （G1-G3）， no regional lymph node metastasis （N0）， and different subtypes （P<0.01）. Vimentin mRNA expression was higher in tissues from patients with lymph node metastasis than in patients without lymph node metastasis and normal samples. Vimentin protein level was decreased in HCC tissues （P<0.01）. Vimentin gene has 4 mutations which can induce change in the primary structure of Vimentin protein and patients with Vimentin gene mutation had short disease free survival time （P<0.01）. The mRNA expression of Vimentin was negatively associated with HCC cell purity （P<0.01） but was positively associated with the infiltration levels of cancer-associated fibroblasts， M2 macrophages， myeloid dendritic cell and other immune cells in tumor microenvironment （P<0.01）. Association analysis results showed that the expression of Vimentin was correlated with the STAT3 expression in HCC tissues （P<0.01）. As for the animal experiment， Vimentin mRNA level and protein levels of total Vimentin and p-Vimentin in liver tssue， Vimentin protein level in liver tissue nucleus， Vimentin in rat serum， ROCK2， AURKB， STAT3 and p-STAT3 in liver tissues were up-regulated （P<0.01） and protein level of negative regulator ZBP-89 was reduced in the model group （P<0.01） compared with those in the normal group. Activity of Caspase-3 in liver tissue increased and the ROCK1 protein level was increased in the model group compared with those in the normal group. STAT3 inhibitor， gp130 inhibitor， and medium-dose and high-dose Jianpi Yiqi prescription all can reduce the secretory Vimentin protein in serum， protein levels of total Vimentin and p-Vimentin in liver tissues， and Vimentin in liver tissue nucleus， and the protein levels of STAT3/Vimentin signaling pathway-related molecules， such as STAT3， p-STAT3， ROCK2， and AURKB and up-regulate the protein level of negative regulator ZBP-89 and activity of Caspase-3 （P<0.05， P<0.01）. Effect of medium-dose or high-dose Jianpi Yiqi prescription on Vimentin mRNA expression， STAT3 protein expression， ZBP-89 protein expression， ROCK2 protein expression， AURKB protein expression and Caspase-3 activity was not significantly different from that of STAT3 inhibitor. ConclusionVimentin， an important inflammatory molecule， is closely related to the occurrence and development of HCC and its expression， subcellular location and function may be affected by cancer-associated fibroblasts， M2 macrophages， myeloid dendritic cell， and IL-6/STAT3 signaling pathway， particularly by STAT3 molecule. Jianpi Yiqi prescription may exert therapeutic effect on HCC via regulating Vimentin through the STAT3/Vimentin signaling pathway.

Effect of intravitreal injection of anti-vascular endothelial growth factor agents on systemic concentration of vascular endothelial growth factor / 国际眼科杂志(Guoji Yanke Zazhi)

Chorioretinal disease has become a significant problem affecting human vision. Abnormal expression of vascular endothelial growth factor(VEGF)leads to increased fundus permeability and neovascularization. Vitreous injection of anti-VEGF agents can rapidly inhibit the level of VEGF in the eye and effectively control the development of the disease. At present, anti-VEGF agents are widely administered in ophthalmology. However, studies have shown that intravitreal anti-VEGF agents can reduce plasma VEGF concentration after entering the circulatory system, and the pointless off-target effects of drugs may lead to systemic adverse reactions. For elderly patients, patients with serious comorbidities, lactating women, premature infants and other special populations, attention should be paid to systemic VEGF inhibition after multiple injections. In this paper, in order to provide reference for clinical anti-VEGF therapy, the pharmacokinetics therapy, systemic adverse reactions, contralateral eye effects, and effects of anti-VEGF on breast milk and preterm infants were discussed, and the systemic effects of vitreous injection of anti-VEGF agents were reviewed.

Intervention Effect of Qufeng Gutong Babu Ointment on Rat Model of Osteoarthritis with Cold-dampness Obstruction Based on PI3K/Akt Signal Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of Qufeng Gutong Babu ointment （QFGT） on rats with osteoarthritis （OA） with cold-dampness obstruction， and preliminarily clarify its mechanism. MethodSD male rats were divided into 6 groups， namely， the blank group， model group， positive control drug Huoxue Zhitong ointment （HXZTG） group （1.26 cm2·d-1）， and low， medium， and high-dose QFGT group （75， 150， 300 mg·d-1）. OA model was prepared by joint cavity injection of papain and L-cysteine. On the second day of modeling， climate factors were applied to establish an animal model of combination of disease and syndrome of OA rats with cold-dampness obstruction. Standard VonFrey fiber was used to evaluate the threshold of mechanical pain. Weight bearing difference score and joint function score of both hind limbs were recorded. Hematoxylin-eosin （HE） staining and safranine fixation green staining were used to observe the pathological changes and cartilage degeneration of rat knee joint. Immunohistochemistry （IHC） was used to detect the expression of interleukin-1β （IL-1β）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α）， matrix metalloproteinase-9 （MMP-9）， and cathepsin K （CTSK）. Western blot was used to detect the protein expression of kinase B （Akt）， phosphorylated protein kinase B （p-Akt）， phosphatidylinositol 3-kinase （PI3K）， nuclear factor 1 （NFATc1）， MMP-9， and CTSK in T cells. ResultCompared with the normal group， the model group showed significant mechanical pain sensitivity reaction after modeling （P<0.01）， and the weight bearing difference of both hind limbs and joint function score were significantly increased （P<0.05， P<0.01）. Compared with the model group， both the high-dose QFGT group and the HXZTG group significantly reduced the mechanical pain sensitivity， weight difference， and joint function score of rats （P<0.05， P<0.01）， and the medium-dose QFGT group also improved the joint function to a certain extent， and the degeneration of the knee joint cartilage of rats was significantly reduced （P<0.05， P<0.01）. QFGT and HXZTG both inhibited the protein expression of IL-1β， IL-8， TNF-α， MMP-9， CTAK， PI3K， p-Akt， Akt， and other related proteins in articular cartilage of rats with OA to a certain extent （P<0.05， P<0.01）. ConclusionQFGT can inhibit the release of inflammatory factors and matrix metalloproteinases by inhibiting the PI3K/Akt signal pathway in articular articular cartilage of rats with OA with cold-dampness obstruction， thus ultimately weakening local cartilage degeneration and improving joint function.

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.

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.

Impact of sinonasal anatomic changes after endoscopic anterior skull base surgery on nasal airflow and air conditioning: a computational fluid dynamics study / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the impact of the sinonasal anatomic changes after endonasal endoscopic anterior skull base surgery on the nasal airflow and heating and humidification by computational fluid dynamics (CFD), and to explore the correlation between the postoperative CFD parameters and the subjective symptoms of the patients. Methods: The clinical data in the Rhinology Department of the First Affiliated Hospital of Zhengzhou University from 2016 to 2021 were retrospectively analyzed. The patients received the endoscopic resection of the anterior skull base tumor were selected as the case group, and the adults whose CT scans had no sinonasal abnormalities were chosen as the control group. The CFD simulation was performed on the sinonasal models after reconstructed from the patients' sinus CT images during the post-surgical follow-up. All the patients were asked to complete the Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) to assess the subjective symptoms. The comparison between two independent groups and the correlation analysis were carried out by using the Mann-Whitney U test and the Spearman correlation test in the SPSS 26.0 software. Results: Nineteen patients (including 8 males and 11 females, from 22 to 67 years old) in the case group and 2 patients (a male of 38 years old and a female of 45 years old) in the control group were enrolled in this study. After the anterior skull base surgery, the high-speed airflow moved to the upper part of the nasal cavity, and the lowest temperature shifted upwards on the choana. Comparing with the control group, the ratio of nasal mucosal surface area to nasal ventilation volume in the case group decreased [0.41 (0.40, 0.41) mm-1 vs 0.32 (0.30, 0.38) mm-1; Z=-2.04, P=0.041], the air flow in the upper and middle part of the nasal cavity increased [61.14 (59.78, 62.51)% vs 78.07 (76.22, 94.43)%; Z=-2.28, P=0.023], the nasal resistance decreased [0.024 (0.022, 0.026) Pa·s/ml vs 0.016 (0.009, 0.018) Pa·s/ml; Z=-2.29, P=0.022], the lowest temperature in the middle of the nasal cavity decreased [28.29 (27.23, 29.35)℃ vs 25.06 (24.07, 25.50)℃; Z=-2.28, P=0.023], the nasal heating efficiency decreased [98.74 (97.95, 99.52)% vs 82.16 (80.24, 86.91)%; Z=-2.28, P=0.023], the lowest relative humidity decreased [(79.62 (76.55, 82.69)% vs 73.28 (71.27, 75.05)%; Z=-2.28, P=0.023], and the nasal humidification efficiency decreased [99.50 (97.69, 101.30)% vs 86.09 (79.33, 87.16)%; Z=-2.28, P=0.023]. The ENS6Q total scores of all patients in the case group were less than 11 points. There was a moderate negative correlation between the proportion of the inferior airflow in the post-surgical nasal cavity negatively and the ENS6Q total scores (rs=-0.50, P=0.029). Conclusions: The sinonasal anatomic changes after the endoscopic anterior skull base surgery alter the nasal airflow patterns, reducing the efficiency of nasal heating and humidification. However, the post-surgical occurrence tendency of the empty nose syndrome is weak.