BACKGROUND:Coptis chinensis can clear heat,dry dampness,relieve fire,and detoxify.Coptis chinensis and its components have a significant protective effect on cerebral ischemia.The action mechanism of anti-cerebral ischemia of Coptidis Rhizoma Alkaloids was explored based on network pharmacology and transcriptome sequencing. OBJECTIVE:Based on the study of the protective effects of Coptidis Rhizoma Alkaloids on cerebral ischemia of rats,the action mechanism of Coptidis Rhizoma Alkaloids intervention in cerebral ischemia was investigated by using network pharmacology and transcriptome sequencing technology. METHODS:The SD rats were randomly divided into sham operation group,ischemia/reperfusion group,positive drug group,and Coptidis Rhizoma Alkaloids group.The ischemia/reperfusion model of middle cerebral artery occlusion was prepared by modified thread method in the latter three groups.No thread was inserted and the other operations were the same in the sham operation group.TTC staining,Longa 5 neurological deficient score,hematoxylin and eosin staining,and Nissl staining were used to evaluate the protective effect of Coptidis Rhizoma Alkaloids on ischemia/reperfusion model rats.Transcriptome sequencing was performed on the brain tissues of rats in sham operation group,ischemia/reperfusion group,and Coptidis Rhizoma Alkaloids group.Differentially expressed genes,gene Ontology analysis,Kyoto encyclopedia of genes and genomes analysis,and Correlation Analysis of Transcriptomics and Network Pharmacology were used to elucidate the effect of Coptidis Rhizoma Alkaloids on cerebral ischemia.Finally,ELISA and immunofluorescence staining were used to verify the key targets of Coptidis Rhizoma Alkaloids in the intervention of cerebral ischemia. RESULTS AND CONCLUSION:(1)Coptidis Rhizoma Alkaloids treatment decreased the Longa 5 neurological deficit scores and cerebral infarction area of ischemia/reperfusion model rats,increased the number of neurons and Nissl bodies.(2)Differentially expressed gene after Coptidis Rhizoma Alkaloids treatment analyzed by functional enrichment analysis of gene ontology includes biological processes such as inflammatory reaction and positive regulation of mitogen-activated protein kinase cascade.The enrichment analysis of Kyoto gene and genome encyclopedia analysis pathway mainly involves interleukin-17 signaling pathway,neuroactive ligand-receptor interaction,cyclic adenosine-3′,5′-mconophosphate signaling pathway and so on.(3)Analysis of transcriptomics showed that the main genes regulated by Coptidis Rhizoma Alkaloids were prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.(4)Network pharmacology analysis revealed that nine components in Coptidis Rhizoma Alkaloids may exert their effects by associating with 87 targets related to prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.(5)ELISA and immunofluorescence staining results further confirmed that Coptidis Rhizoma Alkaloids regulated the expression of prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.(6)It is concluded that Coptidis Rhizoma Alkaloids treatment can significantly improve the injury in ischemia/reperfusion model rats,possibly by regulating prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.

Objective To investigate the value of the peripheral blood neutrophil to lymphocyte ratio(NLR)before nimotuzumab combined with neoadjuvant chemotherapy in predicting the short-term efficacy of neoadjuvant therapy for advanced oral squamous cell carcinoma(OSCC).Methods With the approval of the Ethics Committee and the in-formed consent of the patients,59 patients with stage Ⅲ and Ⅳ OSCC who were admitted to the Oral and Maxillofacial Surgery Department of the First Hospital of Shanxi Medical University from September 2020 to June 2023 were en-rolled.All the patients had complete clinical data,were pathologically diagnosed with squamous cell carcinoma,and re-ceived preoperative and received preoperative nimotuzumab+TP(docetaxel+cisplatin)neoadjuvant chemotherapy.The clinical data were analyzed,and the neutrophil and lymphocyte counts in peripheral blood were collected before and after nimotuzumab combined with neoadjuvant chemotherapy.The NLR was calculated,and the threshold value was calculated using the receiver operating characteristic(ROC)curve.Patients were divided into a high NLR group and a low NLR group according to the NLR threshold before nimotuzumab combined with neoadjuvant chemotherapy with TP.The clinical efficacy after nimotuzumab combined with neoadjuvant chemotherapy with TP was evaluated according to the evaluation criteria for solid tumor efficacy,and the correlation between the NLR and recent neoadjuvant therapy effi-cacy was analyzed.Immunohistochemical staining was used to detect the expression of epidermal growth factor receptor(EGFR)in OSCC tissues before and after nimotuzumab combined with neoadjuvant chemotherapy with TP and to ana-lyze whether the expression of EGFR differed among the different NLR groups.Results A total of 59 patients with ad-vanced OSCC were included.According to the ROC curve,the NLR threshold was 2.377,and the patients were divided into a＜2.377 group(low NLR group),with 24 patients,and a＞2.377 group(high NLR group),with 35 patients.The short-term neoadjuvant therapy effect was significantly greater in the lower NLR group than in the higher NLR group(P＜0.05);EGFR expression in both the low NLR group and the high NLR group decreased after nimotuzumab com-bined with neoadjuvant chemotherapy with TP,and the decrease in the low NLR group was significantly greater than that in the high NLR group(P＜0.05).Conclusion A low NLR before nimotuzumab combined with neoadjuvant che-motherapy with TP is associated with better neoadjuvant therapy outcomes,and such patients are more likely to benefit from preoperative nimotuzumab combined with neoadjuvant chemotherapy.

ObjectiveTo reveal the molecular mechanism of Angong Niuhuangwan（AGNH） in improving traumatic brain injury（TBI） based on single cell sequencing. MethodSeventy-five male SD rats were randomly divided into the sham group， model group， piracetam group（3.6 g·kg^-1）， AGNH low- and high-dose groups（0.09， 0.27 g·kg^-1）， with 15 rats in each group. In addition to the sham group， the other 4 groups used the modified Feeney free-fall impact method to prepare TBI model， and the drugs were administered by gavage immediately after modeling， 24 hours later， the modified neurological deficit score（mNSS） was performed， and brain tissue was isolated to determine the degree of cerebral edema. Hematoxylin-eosin（HE） staining was used to observe the injury degree in the cortex， CA1 region and CA3 region of brain tissue. The expression levels of cyclooxygenase-2（COX-2）， interferon regulatory factor 1（IRF1）， Janus kinase 2（JAK2） and suppressor of cytokine signaling 3（SOCS3） were observed by immunofluorescence（IF） staining. The levels of interleukin（IL）-6， IL-18， IL-1β， IL-17A， tumor necrosis factor-α（TNF-α）， Caspase-1 and nucleotide binding oligomerization domain（NOD）-like receptor heat protein domain associated protein 3（NLRP3） inflammasome were determined by enzyme-linked immunosorbent assay（ELISA）. The regulation of AGNH on each cell population was analyzed by single cell sequencing， and differentially expressed genes were analyzed by Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG）， which led to construct microglia differentially expressed gene network to search for the key targets， and validated by ELISA and IF. ResultCompared with the sham group， the mNSS and brain water content were significantly increased in the model group（P<0.01）. Compared with the model group， mNSS and brain water content in the low and high dose AGNH groups were decreased（P<0.05，P<0.01）. HE staining results showed that compared with the sham group， the cells in the cerebral cortex and hippocampus of rats in the model group were seriously lost， and the cells were arranged loosely（P<0.01）. Compared with the model group， AGNH could significantly increase the density of neurons in the CA1 and CA3 regions of the cerebral cortex and hippocampus， making the arrangement more compact， as well as improved cell morphology（P<0.05，P<0.01）. ELISA and IF staining showed that AGNH could reduce the levels of Caspase-1， IL-17A， TNF-α， NLRP3 and COX-2 in brain tissue of TBI rats（P<0.05， P<0.01）. A total of 13 cell subsets were identified by single cell sequencing， among which microglia played an important role in neuroimmunity. The results of GO enrichment analysis of differentially expressed genes in microglia showed that AGNH improved TBI in response to inflammation and TNF-α. KEGG enriched IL-17 signaling pathway， TNF signaling pathway， Toll-like receptor signaling pathway， etc. The results of network analysis showed that the key targets of AGNH in regulating TBI might be IL-6， IL-1β， JAK2， SOCS3， IRF1. IF and ELISA verification results showed that compared with the sham group， SOCS3 expression in microglia was decreased in the model group， and the expressions of IL-6， IL-1β， JAK2 and IRF1 were increased（P<0.01）. Compared with the model group， AGNH could increase the expression of SOCS3， decrease the expression of IL-6， IL-1β， JAK2， IRF1 （P<0.05， P<0.01）. ConclusionAGNH can reduce the degree of brain edema and brain injury， decrease the expression of inflammatory factors， and inhibit the expression of NLRP3 and its downstream Caspase-1 in TBI rats， which may act on the targets of IL-6， IL-1β， JAK2， IRF1 and SOCS3 in microglia.

Objective:To investigate the application effect of problem-based learning (PBL) combined with scenario simulation in nursing teaching of needlestick injuries.Methods:A total of 123 undergraduates majoring in nursing were selected as research subjects from the classes of 2020 and 2021 in a medical university. The 60 undergraduates in the class of 2020 were established as control group and were given PBL teaching, and the 63 undergraduates in the class of 2021 were established as experimental group and were given PBL combined with scenario simulation. The two groups were compared in terms of theoretical score, skill examination score, and knowledge-attitude-practice (KAP) score of needlestick injury knowledge. SPSS 25.0 was used to perform the t-test, the chi-square test, and the rank sum test. Results:Compared with the control group, the experimental group had significantly higher scores of theoretical examination [(84.43±5.03) vs. (80.30±4.81), P<0.001] and skill examination [(88.40±4.26) vs. (83.55±5.84), P<0.001], as well as significantly higher scores of knowledge [(14.46±1.03) vs. (13.18±1.23), P<0.001], attitude [(52.59±3.09) vs. (48.05±3.06), P<0.001], and practice [(67.37±4.28) vs. (62.17±3.92), P<0.001] in KAP questionnaire. Conclusions:PBL combined with scenario simulation teaching can effectively improve the knowledge of protection against needlestick injuries and related skills in nursing students, enhance their awareness of needlestick injuries, and promote the protective behavior against needlestick injuries.

The accessory parotid gland is a normal salivary gland tissue completely separated from the main parotid gland,which is mostly located in the middle of the face.Any tumor originating from the parotid gland can occur in the accessory parotid gland.Due to the special location of the disease,the diagnosis and treatment of accessory parotid gland tumor is more difficult and more dangerous than that of the parotid gland tumor.This article reviews the anatomy and physiology,clinical diagnosis and treatment of accessory pa-rotid gland tumors,in order to provide guidance for clinical diagnosis and treatment.

Objective To investigate clinical and epidemiological features of pneumocystis jirovecii pneumonia (PJP) in kidney transplant recipients. Methods Clinical data of 68 kidney transplant recipients admitted from July, 2021 to December, 2021 were collected. All patients were divided into the PJP group (n=11), common pulmonary infection group (n=24) and non-pneumonia group (n=33) according to the status of pulmonary infection. The incidence and treatment of PJP after kidney transplantation were analyzed. Basic characteristics and laboratory parameters of the recipients were compared among all groups. The genotyping and transmission map of PJP patients were evaluated. Results Among 64 kidney transplant recipients, 11 cases were definitely diagnosed with PJP. The most common clinical manifestations included elevated body temperature, and dry cough complicated with progressive dyspnea. Chest CT scan showed diffuse interstitial inflammation and ground glass-like lesions of bilateral lungs in all patients. After diagnosis, all patients were orally given with compound sulfamethoxazole for 3-4 weeks. Two patients received non-invasive ventilator-assisted ventilation due to severe lung infection and dyspnea, and the remaining patients were given with nasal cannula oxygenation. One patient experienced elevated serum creatinine level upon discharge, and developed renal allograft failure. The remaining 10 recipients with PJP obtained normal renal allograft function, and no recipient died. Compared with the non-pneumonia group, the rejection rate was higher, the length of hospital stay was longer, the lymphocyte count was less, the lymphocyte proportion was lower, the levels of C-reactive protein, serum creatinine and lactate dehydrogenase were higher, and the levels of serum albumin was lower and CD4⁺T cell count was less in the PJP group (all P < 0.05). Compared with common pulmonary infection group, the lymphocyte count was less, the lymphocyte proportion was lower, the CD4⁺T cell count was less and 1, 3-β-D- glucan (BDG) level was higher in the PJP group (all P < 0.05). No new genotype was detected in 10 of the 12 testing samples. It was considered that PJP mainly depended on two transmission chains and two independent transmission individuals. Conclusions Kidney transplant recipients are prone to pneumocystis jirovecii (PJ) infection due to impaired cellular immune function. The most common clinical manifestations consist of elevated body temperature and dry cough complicated with progressive dyspnea, accompanied by headache and fatigue in partial patients. Chest CT scan shows diffuse interstitial inflammation and ground glass-like lesion of bilateral lungs. PJ may be transmitted through respiratory tract. Small-scale PJP might occur in the follow-up outpatient of kidney transplant recipients. Preventive measures should be delivered in a timely manner.

Objective: To investigate the status of insomnia, Internet addiction, and depressive symptoms among medical students and to analyze the effect of Internet addiction on insomnia and the mediating role of depressive symptoms, in order to provide a basis for the development of targeted interventions and measurements for medical students. Methods: A stratified whole group sampling method was used to select full-time college students from three medical universities in Anhui Province. The Chinese version of Insomnia Severity Index (ISI), Internet Addiction Test (IAT) scale and 9-item Patient Health Questionnaire (PHQ-9) were used to evaluate the symptoms of insomnia, Internet addiction and depressive in students. A multivariate Logistic regression analysis was used to explore the factors influencing insomnia among medical students and to analyze the relationship between insomnia with Internet addiction and depressive symptoms, respectively. Results: The overall rate of Internet addiction was 49.5%, depressive symptoms was 39.5%, insomnia was 18.6%. High academic stress, and the presence of surrounding people diagnosed with COVID-19 were associated with a higher risk of insomnia ( P <0.05). The higher the level of Internet addiction (mild, OR =2.60; moderate/severe, OR =4.21) and depression. (mild, OR =6.35; moderate/severe, OR =19.32), the higher the risk of insomnia. Mediated effect analysis showed that Internet addiction had a direct predictive effect ( β =0.02, P <0.05) on insomnia and also indirectly affected insomnia through depression (indirect effect=0.07，95% CI =0.06-0.08). Conclusion The detected rates of insomnia, Internet addiction and depressive symptoms are high among medical students in Anhui Province, and Internet addiction and depressive symptoms are risk factors for insomnia, which should be given more attention and appropriate interventions when necessary to improve their physical and mental health.

To analyze the endoscopic ultrasonography (EUS) and histopathological features of esophageal epithelial malignant tumors misdiagnosed as esophageal submucosal tumors (SMT), data of patients diagnosed as having esophageal SMT preoperatively but confirmed as esophageal epithelial malignant tumor by pathology after operation in Nanjing Drum Tower Hospital from January 2012 to December 2020 were retrospectively analyzed, and the clinical data including age, gender, size and location of the lesion, origin and echo of the lesion under EUS, endoscopic treatment and postoperative pathology were recorded. Among the 11 patients, there were 9 males and 2 females, aged (65.5±6.2) years. The length diameter of 9 lesions was ≤2 cm, and 8 lesions were located in the middle thoracic esophagus. Among the 11 patients, 10 underwent EUS before operation. The lesions originated from submucosa in 6 cases, muscularis propria in 2 cases and muscularis mucosa in 2 cases. The echo of the lesions was hypoechoic in 9 cases and isoechoic in only 1 case. Of the 11 patients, 3 underwent endoscopic mucosal resection, 6 underwent endoscopic submucosal dissection, and 2 underwent submucosal tunneling endoscopic resection. The histopathological types included 3 cases of moderately to poorly differentiated squamous cell carcinoma, 3 cases of basaloid squamous cell carcinoma, 2 cases of adenoid cystic carcinoma (including 1 case of adenoid cystic carcinoma colliding with squamous cell carcinoma), 2 cases of adenocarcinoma, and 1 case of esophageal sarcomatoid carcinoma with basaloid squamous cell carcinoma. Endoscopic manifestations of submucosal eminence in esophageal epithelial malignant tumors are extremely rare. EUS is helpful for differential diagnosis, and diagnostic treatment can make a definite diagnosis.

Clinical data of 26 patients with proton pump inhibitor dependent gastroesophageal reflux disease (GERD) who underwent anti-reflux mucosectomy (ARMS) in Nanjing Drum Tower Hospital from July 2017 to December 2020 were reviewed, and the GERD questionnaire (GERD-Q) score, the short-form reflux-qual (RQS) score, esophageal motility and 24 h esophageal pH parameters before and after ARMS were compared. With a median follow-up period of 18.4 months (6-27 months), 23 (88.5%) patients reported symptomatic improvement and 15 (57.7%) patients discontinued the use of proton pump inhibitors. After ARMS, the mean scores of GERD-Q (6.23 VS 13.19, P=0.004) and RQS (26.67 VS 10.98, P<0.001) were significantly improved, the mean DeMeester score (10.69 VS 53.15, P<0.001), the mean acid exposure time percentage (3.56% VS 9.92%, P<0.001) and the mean number of acid reflux episodes (36.9 VS 139.9, P=0.001) were lower, and the mean rest pressure at lower esophageal sphincter (LES) (25.19 mmHg VS 13.63 mmHg, P<0.001) and the mean distal contractile integral (1 819.15 mmHg·s·cm VS 1 007.67 mmHg·s·cm, P<0.001) were significantly increased compared with those before surgery. ARMS has significant short-term efficacy in the treatment of proton pump inhibitor dependent GERD, which can effectively improve reflux symptoms and life quality of patients, and strengthen the rest pressure of LES and peristalsis of the esophageal body.

Objective:To establish the normal values of water-perfused high resolution esophageal manometry (HREM)(GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing in Chinese population.Methods:From September 1, 2019 to June 30, 2020, 91 healthy volunteers receiving water-perfused HREM (GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing were selected from 9 hospitals (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; the First Affiliated Hospital of Dalian Medical University; the Second Hospital of Hebei Medical University; the Second Affiliated Hospital, Naval Medical University; the First Affiliated Hospital, Sun Yat-sen University; the First Affiliated Hospital, University of Science and Technology of China; Aviation General Hospital of China Medical University; the Affiliated Hospital of Medical School of Nanjing University and the First People′s Hospital of Yichang). Parameters included the position of the upper and lower edges of the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), the length of the LES and UES, the position of the pressure inversion point (PIP), the resting pressure of UES and LES and swallow-related parameters such as the distal contraction integral (DCI), 4 s integrated relaxation pressure (IRP), distal latency (DL) and UES residual pressure. One-way analysis of variance, post-hoc test and sum rank test were used for statistical analysis.Results:A total of 87 healthy volunteers were enrolled, including 40 males and 47 females, aged (38.5±14.2) years old (ranged from 19 to 65 years old). The position of the upper and lower edges of the LES was (42.7±2.8) and (45.6±2.8) cm, respectively, the length of the LES was (2.9±0.4) cm, and the position of PIP was (43.3±2.8) cm. The position of the upper and lower edges of the UES was (18.1±3.0) and (22.6±2.0) cm, respectively, and the length of the UES was (4.8±1.0) cm. The resting pressure of LES and UES was (17.4±10.7) and (84.1±61.1) mmHg (1 mmHg=0.133 kPa), respectively. The DCI value at solid swallowing was higher than those at water swallowing and semisolid swallowing ((2 512.4±1 448.0) mmHg·s·cm vs. (2 183.2±1 441.2) and (2 150.8±1 244.8) mmHg·s·cm), and the differences were statistically significant ( t=-4.30 and -3.74, both P<0.001). The values of 4 s IRP at semisolid swallowing and solid swallowing were lower than that at water swallowing ((4.6±4.1) and (4.9±3.9) mmHg vs. (5.4±3.9) mmHg), and the differences were statistically significant ( t=3.38 and 2.09, P=0.001 and 0.037). The DL at water swallowing was shorter than those at semisolid swallowing and solid swallowing ((8.5±1.8) s vs. (9.8±2.2) and (10.6±2.8) s), and the DL at semisolid swallowing was shorter than that at solid swallowing, and the differences were statistically significant ( t=-10.21, -13.91 and -4.68, all P<0.001). The UES residual pressure at water swallowing was higher than those at semisolid swallowing and solid swallowing (9.5 mmHg, 6.5 to 12.3 mmHg vs. 8.0 mmHg, 4.5 to 11.7 mmHg and 5.5 mmHg, 2.0 to 9.3 mmHg), and the UES residual pressure at semisolid swallowing was higher than that at solid swallowing, and the differences were statistically significant ( t=3.48, 10.30 and 6.35, all P<0.001). Conclusions:The normal values of water-perfused HREM (GAP-36A) in Chinese population at resting period, water swallowing, semisolid swallowing and solid swallowing can provide a reference basis for clinical diagnosis and treatment for patients receiving water-perfused HREM examination.