italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Objective To analyze the factors associated with pain after arthroscopic rotator cuff bridge suture.Methods According to the inclusion and exclusion criteria,the data of 112 patients with unilateral rotator cuff injury who received arthroscopic bridge suture in our department were collected and were investigated in the form of telephone follow-up.In this study,SPSS 23.0 was used to input data and conduct statistical analysis.Logistic regression analysis was used to analyze the correlation between the above influencing factors and postoperative pain.Results A total of 112 patients were included for statistical analysis,single factor analysis revealed,including course of disease,smoking history,preoperative University of California,Los Angeles(UCLA)score,Constant score,numeric rating scale(NRS),size of rotator cuff tear,whether it was full-thickness tear and degree of tendon retraction might be related to postoperative pain(P<0.05).The age,gender,body mass index(BMI),drinking history,diabetes and hypertension were not related to postoperative pain(P>0.05).Multiple linear regression analysis concluded that there were four factors related to postoperative pain,and the correlation degree was preoperative NRS,preoperative UCLA score,tear size and smoking history.Conclusion The causes of postoperative pain after arthroscopic rotator cauff repair are complex and diverse.Analyzing the cause of postoperative pain can effectively reduce the pain of patients and promote the recovery of shoulder joint function.

ObjectiveTo investigate the potential mechanisms of Jiawei Jingqin Decoction （加味荆芩汤） in the treatment of rosacea. MethodsFifty 8-week-old female BALB/c mice were randomly divided into normal control group， model group， and Jiawei Jingqin Decoction low， medium， and high-dose groups， with 10 mice in each group. Except for the normal control group， mice in the other groups were injected with 40μl of antimicrobial peptide LL-37 at a concentration of 320 μmol/L on the back， repeated once every 12 hours for a total of 4 injections， to induce the rosacea mouse model. The mice in the normal control group were injected with 40 μl of PBS solution at the same time. After successful modeling， the mice in the Jiawei Jingqin Decoction low， medium， and high-dose groups were orally administered Jiawei Jingqin Decoction at doses of 4.35， 8.71， and 17.42 g/（kg·d） respectively， while the mice in the normal control group and the model group were orally administered 20 ml/（kg·d） of normal saline. All groups were treated once daily for 5 days. The changes in skin lesions were observed， and the erythema area was measured and scored. Skin tissue at the injection site was collected for histopathological examination using HE staining， and the number of mast cells was detected using toluidine blue staining. The levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-alpha （TNF-α） in the skin lesion tissues were measured using the ELISA method. The mRNA expression levels of key factors in the innate immune response pathway of rosacea disease mechanism， including Toll-like receptor 2 （TLR2）， downstream molecules serine protease kallikrein 5 （KLK5） and matrix metalloproteinase 9 （MMP-9）， as well as related inflammatory factors （IL-1β， IL-6， TNF-α）， and adaptive immune CD4⁺ T cell-related factors interferon-gamma （INF-γ） mRNA were detected using RT-qPCR. Immunohistochemical staining was performed to detect the protein expression of KLK5， MMP-9， and the number of CD4⁺ T-positive cells. Western blot analysis was used to determine the protein expression levels of CD4⁺ T cell-related factors including IFN-γ， CC chemokine receptor 5 （CCR5）， signal transducer and activator of transcription 1 （STAT1）， signal transducer and activator of transcription 3 （STAT3）. ResultsThe skin at the injection site on the back of mice in the normal control group appeared normal without any skin lesions or erythema， and histopathological examination showed no infiltration of inflammatory cells. The model group had significantly higher erythema scores and larger erythema areas compared to the normal control group （P＜0.05）， and histopathological examination revealed a significant infiltration of inflammatory cells， with some signs of deep connective tissue damage. Compared to the model group， the Jiawei Jingqin Decoction medium and high-dose groups showed a significant decrease in erythema scores and erythema areas （P＜0.05）， as well as a reduction in inflammatory exudates and inflammatory cell infiltration. However， the Jiawei Jingqin Decoction low-dose group did not show significant difference （P＞0.05）， but there was a slight reduction in inflammatory cell infiltration compared to the model group. When compared to the normal control group， the rosacea skin tissues of the model group showed an increase in the number of mast cells， levels of IL-1β， IL-6， TNF-α， mRNA expression of IL-1β， IL-6， TNF-α， TLR2， INF-γ， KLK5， MMP-9， protein expression of KLK5， MMP-9， and the number of CD4⁺ T-positive cells （P＜0.05）. Compared to the model group， the Jiawei Jingqin Decoction medium and high-dose groups showed a decrease in the number of mast cells， levels of IL-1β， mRNA expression of IL-1β， TNF-α， and the number of CD4⁺ T-positive cells. The Jiawei Jingqin Decoction high-dose group showed a decrease in IL-6， TNF-α levels， mRNA expression of IL-6， TLR2， INF-γ， MMP-9， protein expression of MMP-9， KLK5， and the number of CD4⁺ T-positive cells， as well as a decrease in IFN-γ and STAT1 protein expression （P＜0.05） compared to the Model group. ConclusionJiawei Jingqin Decoction has significant improvement effect on the skin symptoms of roseacne in a mouse model. Its mechanism might be related to regulating skin immune inflammatory reactions， thereby reducing the release of pathogenic factors and inflammatory factors.

  Objective  To investigate the occurrence of chronic postsurgical pain (CPSP) among patients with preoperative COVID-19, and further analyze the risk factors for CPSP.  Methods  This study was a ambispective cohort study, with subjects from a completed cohort study with follow-up. We included the clinical data of the patients with preoperative COVID-19 who underwent surgery at Peking Union Medical College Hospital from December 1, 2022 to February 28, 2023. Follow-up was conducted up to 6 months postoperatively, with the primary outcome being CPSP. Multivariate Logistic regression analysis was used to analyze the correlation between COVID-19-related exposure indicators and CPSP.  Results  A total of 4117 surgical patients were included, all of whom had preoperative COVID-19. Among them, 4002 cases had mild symptoms during the acute phase, 62 cases had severe symptoms, and 53 cases were critically ill. At 6th month postoperatively, 1298 cases (31.53%) had long COVID-19 syndrome, and the incidence of CPSP was 5.59% (95% CI: 4.88%-6.28%). After adjusting for confounding factors including age, gender, comorbidities, anesthesia method, and type of surgery, multivariate Logistic regression analysis revealed that critically ill COVID-19 during the acute phase (aOR=3.35, 95% CI: 1.48-7.62, P < 0.001) and presence of long COVID-19 syndrome postoperatively (aOR=2.50, 95% CI: 1.90-3.29, P < 0.001) were associated with CPSP.  Conclusions  It is clear for the first time that critically ill COVID-19 during the acute phase and the presence of long COVID-19 syndrome postoperatively are the risk factors for CPSP among patients with preoperative COVID-19.

This paper summarized Professor YE Jianzhou's experience in treating atopic dermatitis （AD） in children with the method of regulating the heart and treating the spirit. According to the clinical manifestations of itching-sleep psychological disorders in children with AD， and the physiological characteristics of "heart qi is prone to hyperactivity" and "liver qi is prone to hyperactivity" in children， it is believed that heart and spirit disharmony is an important pathogenesis of AD in children.From the concept of holism in traditional Chinese medicine， the principle of regulating the heart and treating the spirit has been proposed for treatment of AD in children， which is based on the theory of "the five zang （脏） organs store the spirit". In the acute stage， it is recommended to clear the heart， drain fire and calm the spirit with self-made Qingxin Ningshen Decoction （清心宁神汤） in modifications. In the chronic stage， the method of nourishing the heart， unblocking the meridians and calming the spirit is recommended， by using self-made Yangxin Anshen Decoction （养心安神汤） with modifications. The method to tranquilize the heart， subdue yang and contain the spirit should be implemented throughout the entire treatment， and yang-subduing and spirit-containing medicinals such as Duanlonggu （Os Draconis Praeparatum）， Duanmuli （Concha Ostreae Praeparatum） and Zhenzhumu （Concha Margaritiferae Usta） are usually used to treat the body and the spirit simultaneously. All these are offered to provide new ideas for the individualized treatment of children with AD.

Objective:To analyze the expression of silent information regulator 2-related enzyme 1 (SIRT1) and its relationship with chondrocyte apoptosis in patients with Kashin-Beck disease (KBD).Methods:Twenty patients with KBD were selected as the KBD group from Guide County, Qinghai Province, and 40 healthy subjects matched by age and sex were selected as the control group. Fasting elbow venous blood of the study subjects was collected, and peripheral blood mRNA levels of SIRT1 and selenoprotein genes [glutathione peroxidase (GPX) 2, GPX3, thioredoxin reductase (TXNRD) 1, TXNRD3, iodothyronine deiodinase Ⅰ (DIO1), and selenophosphate synthetase 2 (SPS2)] were detected by real-time PCR. The correlation between SIRT1 expression and selenoprotein genes in peripheral blood of KBD patients was analyzed by curve fitting method. Meanwhile, normal human chondrocytes cultured in vitro were divided into control group (without any treatment), resveratrol (RES) group (to verify the activation effect of RES on SIRT1), tert-butyl hydroperoxide (tBHP) injury group (oxidative injury model of chondrocyte), and RES protection group (tBHP injury after RES pre protection). The mRNA levels of SIRT1, selenoprotein genes, and apoptosis-related genes [B lymphoblastoma-2 gene (BCL2), BCL2-associated X protein (BAX), nuclear transcription factor κB (NF-κB) p65, and tumor suppressor gene P53] in each group of cells were detected by real-time PCR. Results:In the population study, the peripheral blood SIRT1 mRNA level in the KBD group (1.12 ± 0.38) was lower than that of control group (1.87 ± 0.97), and the difference was statistically significant ( t = 3.31, P = 0.002). According to curve fitting analysis, the mRNA levels of GPX3, TXNRD1, and TXNRD3 in peripheral blood of KBD group increased with the increase of SIRT1 mRNA level ( R2 = 0.48, 0.66, 0.95, P < 0.001). The level of DIO1 mRNA showed a trend of decreased first and then increased with the increase of SIRT1 mRNA level ( R2 = 0.51, P = 0.024). The mRNA levels of GPX2 and SPS2 showed no significant change trend with the increase of SIRT1 mRNA level ( R2 = 0.16, 0.12, P = 0.064, 0.114). In cell studies, compared with the control group (1.00 ± 0.10), the SIRT1 mRNA level in the RES group (1.79 ± 0.07) was higher ( P < 0.05). Compared with tBHP injury group, the RES protection group had higher mRNA levels of selenoprotein genes GPX3, TXNRD1, TXNRD3, and DIO1 ( P < 0.05); the mRNA levels of apoptosis-related genes BAX, P53 and the ratio of BAX/BCL2 were lower, while the mRNA levels of BCL2 and NF-κB p65 were higher ( P < 0.05). Conclusions:KBD patients have low expression of SIRT1. And RES activation of SIRT1 may enhance the antioxidant capacity of chondrocyte by up-regulating the expression of selenoprotein genes, thus inhibiting chondrocyte apoptosis.

Objective:To investigate the role of oxidative stress and silent information regulator 2 homolog 1 (SIRT1) in cartilage injury in Kashin-Beck disease (KBD) by evaluating the level of oxidative stress and the effect of oxidative injury on SIRT1 expression in patients with KBD.Methods:In May 2017, Twenty patients with KBD were selected from Guide County of Qinghai Province as the KBD group, and 40 healthy subjects were selected as the control group, 5 ml elbow venous blood was collected, centrifuged, and the upper plasma was retained. The glutathione peroxidase (GPX) activity and reactive oxygen species (ROS) level were determined by enzyme linked immunosorbent assay (ELISA), and SIRT1 mRNA level was determined by real-time fluorescence quantitative PCR (RT-qPCR). Meanwhile, 150 μmol/L tert-butyl hydroperoxide (tBHP) was selected to damage chondrocytes; and different concentrations of sodium selenite (Na 2SeO 3) were used to intervene in chondrocytes to detect cell viability, and appropriate concentration of Na 2SeO 3 was selected for pre protection. Total RNA and DNA of chondrocytes were extracted. The mRNA levels of SIRT1, DNA methyltransferase 1 (DNMT1), and the DNA methylation level in the SIRT1 promoter region were determined by RT-qPCR. At the same time, Hoechst 33342 staining was used to detect chondrocyte apoptosis. Results:The plasma GPX activity [(35.48 ± 8.82) U/g·Hb] in KBD group was lower than that in control group [(40.43 ± 6.68) U/g·Hb, t = - 2.43, P = 0.018], and the ROS level [(577.10 ± 96.92) U/ml] was higher than that in control group [(526.44 ± 62.63) U/ml, t = 2.13, P = 0.043]. GPX activity was positively correlated with SIRT1 mRNA level ( r s = 0.44, P = 0.005), while ROS level was negatively correlated with SIRT1 mRNA level ( r s = - 0.39, P = 0.006). After 48 hours of treatment with 150 μmol/L tBHP (tBHP injury group), the survival rate of chondrocytes decreased to (55.27 ± 2.96)%; and the survival rate of chondrocytes pre-protected with 0.10 μg/ml Na 2SeO 3 (selenium protection group) was significantly higher than that of tBHP injury group ( P < 0.05). Compared with control group, the SIRT1 mRNA level of chondrocytes in tBHP injury group was significantly decreased; while the DNA methylation level in the SIRT1 promoter region, DNMT1 mRNA level and cell apoptosis rate were significantly increased ( P < 0.05). Compared with tBHP injury group, the selenium protection group had higher levels of SIRT1 mRNA in chondrocytes, lower levels of DNA methylation in the SIRT1 promoter region, DNMT1 mRNA, and cell apoptosis rate ( P < 0.05). The apoptosis rate was negatively correlated with SIRT1 mRNA level ( r s = - 0.78, P = 0.004), and positively correlated with the DNA methylation level in the SIRT1 promoter region ( r s = 0.76, P = 0.006). Conclusions:KBD patients have increased levels of oxidative stress, which may be associated with low expression of SIRT1. Oxidative injury may down-regulate SIRT1 expression and promote chondrocytes apoptosis by catalyzing DNA methylation in the SIRT1 promoter region.

新冠病毒感染疫情严重威胁着世界各国人民的生命健康。目前，对病毒感染的防治研究主要集中在抑制病毒与分子受体的结合上。AXL作为新发现的严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）受体，在协助病毒感染人体呼吸系统中发挥着重要作用，是未来临床干预的潜在靶点。本研究对已发表的单细胞测序数据进行整理和分析，发现AXL在年轻人肺细胞中的表达水平明显高于老年人。人胚肺二倍体成纤维细胞（2BS）是衰老研究的公认细胞株。本文采用2BS细胞构建复制性细胞衰老模型，发现年轻细胞中AXL的蛋白水平明显高于衰老细胞，据此推测年轻人感染的风险可能更高，需要注意防护。我们发现一种羊栖菜褐藻多糖硫酸酯组分（SFW-3）可显著下调年轻2BS细胞中AXL的表达水平，表明SFW-3具有一定的抗SARS-CoV-2感染的研究价值，同时表明2BS细胞株也可作为潜在的SARS-CoV-2体外感染模型。
Humans ; SARS-CoV-2 ; Sargassum/metabolism* ; Diploidy ; Sulfates/metabolism* ; COVID-19 ; Polysaccharides/pharmacology* ; Lung

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.