Objective To discuss the medication law of Professor Gu Shizhe in the treatment of insomnia based on various data mining techniques.Methods Clinical information of patients of Professor Gu was collected from the hospital management information system of outpatient clinic of Beijing University of Chinese Medicine(BUCM)and BUCM Famous Elderly TCM Inheritance Research Integrated Platform from January 2018 to October 2022.Professor Gu's books,such as Zhi Zhen Zhi Yao,and Gu Jisheng,Gu Shizhe Yi An Yi Hua Jing Cui,and the medical records from CNKI were screened.WPS Office 5.2.1 was used to build a database of medicine data for Professor Gu's TCM prescriptions,and R 4.2.1 was used for descriptive analysis and Apriori association rule analysis.SPSS Statistics 26.0 was used for clustering analysis,combined with theoretical analysis,to extract Professor Gu's medication law and characteristics in the treatment of insomnia.Results A total of 307 prescriptions were included,involving 250 kinds of Chinese materia medica,among which 30 were high-frequency drugs.The top 5 most frequently used were Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle,Fossilizid,Poria,Bupleuri Radix,and Ziziphi Spinosae Semen.The meridians were mainly liver and lung meridian,and the properties were mainly warm and cold,and the tastes were mainly sweet and bitter.Five core drug groups were obtained by clustering analysis,including Xiaochaihu Decoction,Erchen Decoction,Huanglian Wendan Decoction,Suanzaoren Decoction,Xiaoyao Powder and other prescriptions.Conclusion The characteristics of Professor Gu's treatment of insomnia are to reconcile Shaoyang,clear the heart and soothe the mind;pay attention to yin and yang,regulate the liver;pay attention to the liver,gallbladder,spleen and stomach;the main idea of syndrome differentiation is to reconcile Shaoyang,run the Shaoyang cardinal,and at the same time regulate qi and benefit qi and nourishes yin.

Objectives:To analyze the disease burden and changing trends of non-rheumatic valvular heart disease(NRVHD)from 1990 to 2019 in China. Methods:Based on the Global Burden of Disease 2019 database,we collected data related to NRVHD in China from 1990 to 2019,analyzed the crude incidence rate,crude prevalence rate,crude disability-adjusted life year(DALY),and age-scaled rate of NRVHD during this period,and analyzed the corresponding trends.The grey prediction model GM(1,1)was used to predict the disease burden of NRVHD in China from 2020 to 2029. Results:The crude incidence,crude prevalence,and crude DALY rates of NRVHD increased in China from 7.87/100 000,123.21/100 000,and 9.83/100 000 in 1990 to 22.85/100 000,374.16/100 000,and 11.95/100 000 in 2019;the age-standardized incidence rate and the age-standardized prevalence rate increased from 9.22/100 000 and 169.04/100 000 in 1990 to 15.30/100000 and 262.85/100 000 in 2019 respectively,with females being higher than males;the age-standardized DALY rate declined from 13.43/100 000 in 1990 to 9.07/100 000 in 2019,with females being higher than males.Joinpoint regression model analysis showed an increasing trend in the age-standardized incidence rate and age-standardized prevalence rate,and a decreasing trend in the age-standardized DALY rate(annual average percentage change[AAPC]values of 1.86%,1.72%and-1.66%,respectively),trend of change was statistically significant(all P<0.05).The burden of disease for all age groups from 1990 to 2019 showed an overall increasing trend,and the crude incidence rate,crude prevalence rate and crude DALY rate all increased with age,and the elderly group over 60 years old was the main group of disease burden.The results of the grey prediction model showed that by 2029,the age-standardized incidence rate and age-standardized prevalence rate would increase to 18.51/100 000 and 303.26/100 000,respectively,and the age-standardized DALY rate would decrease to 7.42/100 000. Conclusions:From 1990 to 2019,the age-standardized incidence rate and age-standardized prevalence rate of NRVHD in China showed an increasing trend,and the age-standardized DALY rate all showed a decreasing trend.The disease burden of NRVHD in China remains high.Women and the senior population are the main target groups needing special attention in China,and more targeted prevention and treatment strategies are needed for high-risk population.

Objective:To express NY-ESO-1 epitopes using circular RNA (circRNA) and construct circRNA cancer vaccines using a novel lipid-like material C1, and to evaluate the transfection efficiency and T cell activation potential at cellular level.Methods:In vitro transcription was used to synthesize mRNA and circRNA expressing EGFP and NY-ESO-1 epitopes. Then, they were transfected into COS7 cells and the expression of target proteins were detected in vitro. Lipid-like material C1 and commercial transfection agent TransIT-mRNA were used as delivery systems for mRNA NY-ESO-1 and circRNA NY-ESO-1, and their delivery efficiency was compared. Results:The expression of EGFP was observed under fluorescence microscopy after transfection of mRNA EGFP and circRNA EGFP into COS7 cells for 24 h. The secretion of IFN-γ by T cell receptor-engineered T (TCR-T) cells targeting NY-ESO-1/HLA-A2 was stimulated by COS7-A*02: 01 cells transfected with mRNA NY-ESO-1 and circRNA NY-ESO-1. Compared with mRNA NY-ESO-1, circRNA NY-ESO-1 was able to express the target antigen and stimulate the target cells to release IFN-γ more persistently. The delivery efficiency of C1 material was better than that of commercial transfection reagents when COS7 cells were transfected in vitro. Conclusions:Compared with the linear mRNA, transfection of COS7-A*02: 01 cells with circRNA can lead to more efficient and durable activation of T cells, suggesting that it could be a more suitable candidate for clinical treatment of tumors in the future. The lipid-like material C1 can effectively deliver linear mRNA and circular RNA molecules. This study provides reference for further research on circRNA tumor vaccines.

Objective:To investigate the influencing of inferior mediastinum and esophageal hiatus lymph node metastasis by submucosal different venous divisions of esophagogastric junction (EGJ) invaded in Siewert type Ⅱ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective case-control study was conducted. The clinicopathological data of 547 patients with Siewert type Ⅱ AEG who were admitted to Shanxi Cancer Hospital from January 2018 to December 2021 were collected. There were 461 males and 86 females, aged 61 (range, 33?75)years. Observa-tion indicators: (1) lymph node metastasis rate in different groups; (2) influencing factors of inferior mediastinum lymph node metastasis in Siewert type Ⅱ AEG; (3) influencing factors of esophageal hiatus lymph node metastasis in Siewert type Ⅱ AEG. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Mann-Whitney U test. Count data were described as percentages or absolute numbers, and comparison between groups was conducted using the chi-square test. The univariate analysis was conducted using the corresponding statistical methods based on data type. The Logistic regression model was used for multivariate analysis. Results:(1) Lymph node metastasis rate in different groups. The lymph node metastasis rate in No. 1, 2, 3, 4sa, 4sb, 7, 8a, 9, 11,20, 108, 110 of the 547 patients was 17.37%(95/547), 6.76%(37/547), 46.44%(254/547), 1.65%(9/547), 1.10%(6/547), 23.22%(127/547), 4.39%(24/547), 3.11%(17/547), 3.47%(19/547), 3.66%(20/547), 0.55%(3/547), 4.20%(23/547), respectively. Of the 547 patients, there were 456 cases with proximal of AEG invading submucosal palisade venous of EGJ including 4 cases with inferior mediastinum lymph node metastasis and no case with media mediastinum or up media-stinum lymph node metastasis. There were 91 cases with proximal of AEG invading submucosal perforator venous of EGJ including 18 cases with inferior mediastinum lymph node metastasis, 3 cases with media mediastinum lymph node metastasis and no case with up mediastinum lymph node metastasis. (2) Influencing factors of inferior mediastinum lymph node metastasis in Siewert type Ⅱ AEG. Results of multivariate analysis showed that age, tumor invading submucosal perforator venous of EGJ and histological classification were independent influencing factors for inferior media-stinum lymph node metastasis of Siewert type Ⅱ AEG ( odds ratio=0.93, 23.33, 0.31, 95% confidence interval as 0.87?0.99, 4.18?130.28, 0.12?0.78, P<0.05). (3) Influencing factors of esophageal hiatus lymph node metastasis in Siewert type Ⅱ AEG. Tumor invading submucosal perforator venous of EGJ was an independent influencing factor for esophageal hiatus lymph node metastasis of Siewert type Ⅱ AEG ( odds ratio=14.95, 95% confidence interval as 2.46?90.76, P<0.05). Conclusion:Age, tumor invading submucosal perforator venous of EGJ and histological classification are independent influencing factors for inferior mediastinum lymph node metastasis of Siewert type Ⅱ AEG, and tumor invading submucosal perforator venous of EGJ is an independent influencing factor for esophageal hiatus lymph node metastasis.

ObjectiveTo establish the specific chromatogram and thin layer chromatography（TLC） of Qingxin Lianziyin（QXLZY） benchmark samples， in order to clarify the key quality attributes and provide a reference for the quality evaluation of QXLZY. MethodHigh performance liquid chromatography（HPLC） specific chromatogram of QXLZY benchmark samples was developed by using a YMC Hydrosphere C₁₈ column（4.6 mm×250 mm， 5 μm） with the mobile phase of acetonitrile（A）-0.2% formic acid aqueous solution（B） for gradient elution（0-10 min， 5%-20%A； 10-20 min， 20%A； 20-25 min， 20%-24%A； 25-40 min， 24%-30%A； 40-55 min， 30%-50%A； 55-65 min， 50%-100%A； 65-75 min， 100%A； 75-75.1 min， 100%-5%A； 75.1-90 min， 5%A）， and the detection wavelength was 360 nm. Ultra-high performance liquid chromatography-linear ion trap/orbitrap mass spectrometry（UHPLC-LTQ-Orbitrap MS） with electrospray ionization（ESI） was used to identify the components of QXLZY benchmark samples by accurate relative molecular weight and multilevel MS fragment ion information， the detection conditions were positive and negative ion modes and data dependency scanning mode. TLC identification methods for Ophiopogonis Radix， Lycii Cortex， Nelumbinis Semen， Poria， Astragali Radix and Ginseng Radix et Rhizoma in QXLZY were established. ResultA total of 15 characteristic peaks were identified from Glycyrrhizae Radix et Rhizoma， Plantaginis Semen and Scutellariae Radix， and the relative standard deviations of the retention times of 15 characteristic peaks in 15 batches of QXLZY benchmark samples were≤3% with peak 8（baicalin） as the reference peak. A total of 100 compounds， including flavonoids， organic acids， saponins， amino acids and others， were identified in the benchmark samples by UHPLC-LTQ-Orbitrap MS. The established TLC had good separation and was suitable for the identification of Ophiopogonis Radix， Lycii Cortex， Nelumbinis Semen， Poria， Astragali Radix and Ginseng Radix et Rhizoma in QXLZY. ConclusionThe material basis of QXLZY benchmark samples is basically determined by MS designation and source attribution. The established specific chromatogram and TLC of QXLZY are simple， stable and reproducible， which can provide a reference for the development and quality control of QXLZY.

AIM: To investigate the protective effect of "DuZhong-DangGui" (DZ-DG) on the knee tissue of rats with osteoarthritis (OA) and its regulation role on NLPR3 inflammasome. METHODS: Twenty-four SPF male SD rats, eighteen rats were randomly selected to establish OA model by anteri- or cruciate ligament amputation (ACLT) method, and rats were divided into control group, OA model group, DZ-DG group and positive drug group, 6 in each group, treatment for 8 weeks. The peripheral blood were collected, ELISA was used to detect the levels of IL-1β, IL-6, IL-18, and TNF-α; cartilage tissue of knee joint were collected, HE staining was used to observe pathology changes, OARSI staining was used to observe cartilage calcification and preform quantitative OARSI scoring; immunohistochemistry and TUNEL staining were used to detect the contents of Caspase1 and Collagen II and the number of apoptosis in the tissue, respectively, and western blot was used to detect the protein expressions of matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), p53, p21, NLPR3, apoptosis-associated speck-like protein containing a CARD (ASC) and Pro-Caspase-1. RESULTS: Compared to control group, OA model group rats serum levels of IL-1β, IL-6, IL-18, and TNF - α significantly increased (P<0.01), OARSI scores significantly increased (P<0.01), chondrocyte apoptosis was increased (P<0.01), Caspase-1 content and MMP-13, p53, p21, NLPR3, ASC, Pro-Caspase-1 protein expressions significantly increased (P <0.01), while Collagen II content and TIMP-1 protein expression significantly decreased (P<0.01). Compared with the OA model group, DZ-DG group and positive drug group rats serum levels of IL-1β, IL-6, IL -18 and TNF - α significantly decreased (P< 0.05), chondrocyte apoptosis were significantly decreased (P<0.01), Caspase1 content, MMP-13, p53, NLPR3, Pro-Caspase-1 significantly decreased (P< 0.05), Collagen Ⅱ content and TIMP- 1 protein expression (P<0.01); DZ-DG group rats protein expression of p21 and ASC were decreased (P<0.01). CONCLUSION: The DZ-DG have protection role on cartilage of OA rats, its effect may related to mediation of NLPR3/ASC/Pro-Caspase-1 pathway, to decrease of IL-1β, and inhibition of cell apoptosis.

Klebsiella pneumoniae is one of the common pathogens causing hospital-acquired infection. With the wide use of carbapenem in recent years, carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged around the world. Carbapenemase production is the main cause of resistance to carbapenem antibiotics in Klebsiella pneumoniae. More than 70% of Klebsiella pneumoniae strains produce carbapenemase. Ceftazidime/avibactam (CAZ/AVI) can effectively treat CRKP infection, especially those caused by CRKP that can produce Klebsiella pneumoniae carbapenemase (KPC) or oxaclillinase (OXA)-48. However, it has been reported that CAZ/AVI-resistant CRKP strains have emerged. In this paper, the epidemiology, risk factors, resistance mechanism and treatment of CAZ/AVI-resistant CRKP were summarized to provide reference for clinical treatment.

Objective:To explore the method and effect in repairing the defect of fingertip with lateral V-Y advancement flap with one side palmar proper digital artery.Methods:From October 2014 to May 2019, Department of the Hand and Foot Surgery, the Third People's Hospital of Jining(Yanzhou District People's Hospital of Jining City) treated 34 digits of 27 cases with a defect area of 0.5 cm×0.5 cm-1.5 cm×2.0 cm. A lateral V-Y advancement flap with one side palmar proper artery was used to repair the fingertip defect, and the flap size was 1.7 cm×1.0 cm-4.5 cm×1.5 cm. Twenty cases entered long-time follow-up after operation, with 7 cases lost in follow-up, 16 cases were reviewed at outpatient and 4 by WeChat.Results:All the flaps of 34 digits of 27 cases survived. The color of the flaps were close to or completely normal to the surrounding tissue, the texture was soft and the appearance was good. The TPD of the flap was 2.0-6.0 mm. The follow-up time ranged from 22 to 77 months, with an average of 31.45 months. The flexion and extension function of the digits were good with total range of motion(ROM) of the thumb was > 90 °; total active motion (TAM) of the fingers was 260 °-200 °. The fingers of 1 case had hook nail or hook finger deformity. According to the Evaluation Trial Standard of Upper Limb Partial Function of Hand Surgery of Chinese Medical Association, 18 cases were excellent and 2 cases were good.Conclusion:The lateral V-Y advancement flap with one side palmar proper digital artery is easy to operate. The blood supply of the flap is reliable, with good sensation. The flexion and extension of the digits are good, and the appearance and texture of the flap are good.

Objective:To investigate the application value of self-pulling and latter transection (SPLT) technique in double anti-reflux double-tract reconstruction of totally laparoscopic proximal gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 103 patients with Siewert type Ⅱ adenocarcinoma of esophagogastric junction in clinical stage Ⅰ-Ⅱ who were admitted to Shanxi Cancer Hospital from January 2018 to January 2020 were collected. There were 65 males and 38 females, aged from 45 to 79 years, with a median age of 59 years. Of 103 patients, 49 cases undergoing totally laparoscopic proximal gastrectomy with double-tract reconstruction of SPLT were assigned into the SPLT group, 54 cases undergoing totally laparoscopic proximal gastrectomy with conventional double-tract reconstruction were assigned into the traditional group. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination and telephone inter-view to detect postoperative reflux esophagitis of patients up to December 2021. Measurement data with normal distribution were represented as Mean± SD, and the t test was used for comparison between groups. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and the Wilcoxon test was used for comparison between groups. Count data were described as absolute numbers or percentages, and comparison between groups was performed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Results:(1) Intraoperative situations: the operation time, digestive tract reconstruction time, volume of intraoperative blood loss, the number of inferior mediastinal lymph nodes dissected, cases with auxiliary incisions for the SPLT group were (261±48)minutes, (26±4)minutes, (114±42)mL, 8.0(6.5,9.5), 1, respectively. The above indicators were (244±42)minutes, (30±6)minutes, (118±46)mL, 5.5(4.0,8.0), 9 for the traditional group, respectively. There were significant differences in the digestive tract reconstruction time, the number of inferior mediastinal lymph nodes dissected and cases with auxiliary incisions between the two groups ( t=-3.34, Z=-4.05, χ2=4.72, P<0.05). There was no significant difference in the operation time or volume of intraoperative blood loss between the two groups ( t=1.87, -0.47, P>0.05). (2) Postoperative situations: duration of postopera-tive hospital stay and cases with postoperative complications were (11.5±2.7)days and 4 for the SPLT group, versus (12.5±4.3)days and 9 for the traditional group, showing no significant difference between the two groups ( t=-1.47, χ2=1.68, P>0.05). There were 13 of 103 patients with postopera-tive complications, including 5 cases of left pleural effusion, 4 cases of anastomotic leakage, 2 cases of mild pneumonia, 1 case of incision infection, 1 case of chylous leakage. Four patients had anasto-motic leakage at the esophagojejunostomy, the abdominal esophagus of whom was invaded by more than 1 cm. During the operation, mediastinal drainage tubes were placed through the abdominal wall. The 4 patients were cured after enteral and parenteral nutrition support and adequate drainage, and the remaining patients with complications were cured after symptomatic treatment. (3) Follow-up: of 49 patients in the SPLT group, 43 cases were followed up for (18±4)months. During the follow-up, 1 case showed reflux esophagitis by gastroscopy, with the incidence of 2.33%(1/43). Of 54 patients in the traditional group, 53 cases were followed up for (17±4)months. During the follow-up, 4 cases showed reflux esophagitis by gastroscopy, with the incidence of 7.55%(4/53). There was no significant difference in the incidence of reflux esophagitis between the two groups ( χ2=0.47, P>0.05). Conclusions:SPLT technology is feasible for double anti-reflux double-tract reconstruction of proximal gastrectomy. Compared with traditional double-tract reconstruction of totally laparos-copic proximal gastrectomy, SPLT technology can reduce the auxiliary incisions, increase the number of lower mediastinal lymph nodes dissected, and shorten the digestive tract reconstruction time.

Mitochondrial fission regulator 2 (MTFR2) is associated with mitochondrial fission, while few studies have assessed the associations between MTFR2 expression and clinical characteristics or prognosis of esophageal squamous cell carcinoma (ESCC). In this study, we compared the expression of MTFR2 in 6 ESCC tumors and relative normal tissues by immunohistochemistry (IHC). To assess the effect of MTFR2 expression on clinicopathologic characteristics and survival, 115 paraffin embedded ESCC tissue samples were assessed by IHC staining. Furthermore, the association between clinicopathological properties and MTFR2 expression in patients with ESCC was examined. The survival analysis was performed using the Cox regression models. We found that MTFR2 expression was significantly increased in ESCC tumors compared with normal esophageal epithelial cells. IHC analysis of 115 paraffin embedded ESCC tumor specimens of the patients showed that the expression of MTFR2 was significantly associated with clinical stage (P < 0.001), tumor classification (P < 0.001), histological grade (P < 0.001), and other clinicopathological characteristics. Both univariate and multivariate analyses showed that MTFR2 expression was inversely correlated with the survival of ESCC patients. In conclusion, the expression of MTFR2 is significantly associated with clinicopathologic characteristics and prognosis of ESCC. Thus, MTFR2 expression could serve as a potentially important prognostic biomarker and clinical target for patients with ESCC.