The effects of Shexiang Baoxin pills combined with intracoronary injection of nicorandil on myocardial blood perfusion and short-term prognosis for STEMI patients after PPCI / 药学实践杂志

Objective To observe the effects of Shexiang Baoxin pill combined with intracoronary injection of nicorandil on myocardial perfusion and short-term prognosis after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Methods 151 patients with acute myocardial infarction after PPCI were enrolled in this study. Those patients were admitted to our hospital during January 2017 to January 2018. According to the numerical randomization method, 51 patients were selected as routine treatment group (group A), 50 patients with intracoronary injection of nicorandil (group B) and 50 patients received intracoronary injection of nicorandil plus oral Shexiang Baoxin pills (group C). Intra-operative corrected TIMI frame count (cTFC), postoperative TIMI grade 3 blood flow ratio, 2-hour ECG ST segment fallback >50% index, the incidence of major adverse cardiovascular events (MACE) during hospitalization and the incidence of angina and MACE within 3 months after surgery were evaluated. Results cTFC, 2 hours postoperative ECG ST segment fall >50% index in group B and C were better than group A (P<0.05). The results from group C were better than group B. Group C exhibited better results than group B and C in post-operative angina pectoris 3 months after surgery (P<0.05). Conclusion Shexiang Baoxin pills combined with intra-coronary injection of nicorandil can improve myocardial perfusion and short-term prognosis after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction

Mechanisms of Acupuncture in Improving Alzheimer's Disease Caused by Mitochondrial Damage / 中国结合医学杂志

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases among the elderly and it accounts for nearly 80% of all dementias. The pathogenesis of AD is complicated and enigmatic thus far. The mitochondrial cascade hypothesis assumes that mitochondrial damage may mediate, drive, or contribute to a variety of AD pathologies and may be the main factor in late-onset AD. Currently, there are no widely recognized drugs able to attenuate mitochondrial damage in AD. Notably, increasing evidence supports the efficacy of acupuncture for improving the mitochondrial structure and protecting mitochondrial functions in AD. This review reports the mechanisms by which acupuncture regulates mitochondrial dynamics, energy metabolism, calcium homeostasis and apoptosis. In conclusion, these findings suggest that AD mitochondrial dysfunction represents a reasonable therapeutic target and acupuncture could play a significant role in preventing and treating AD.

Effects of porcine acellular dermal matrix combined with human epidermal stem cells on wound healing of full-thickness skin defect in nude mice / 中华烧伤杂志

Objective: To explore the effects of porcine acellular dermal matrix (ADM) combined with human epidermal stem cells (ESCs) on wound healing of full-thickness skin defect in nude mice. Methods: The morphology of porcine ADM was analyzed by photograph of digital camera, the cell residues in porcine ADM were observed by hematoxylin-eosin (HE) staining, the surface structure of porcine ADM was observed by scanning electron microscope, the secondary structure of porcine ADM was analyzed by infrared spectrometer, the porcine ADM particle size was analyzed by dynamic light scattering particle size analyzer, and the porcine ADM potential was analyzed by nano-particle size potentiometer. The morphology of porcine ADM was observed by inverted fluorescence microscope when it was placed in culture medium for 30 min, 1 d, and 5 d (n=2). The porcine ADM was divided into 5 min group, 10 min group, 20 min group, 30 min group, 60 min group, and 120 min group according to the random number table (the same grouping method below) in static state at normal temperature for the corresponding time to calculate the water absorption by weighing method (n=3). Swiss white mouse embryonic fibroblasts (Fbs) were divided into blank control group (culture medium only), and 50.0 g/L ADM extract group, 37.5 g/L ADM extract group, 25.0 g/L ADM extract group, 12.5 g/L ADM extract group, and 6.5 g/L ADM extract group which were added with the corresponding final concentrations of ADM extract respectively. At post culture hour (PCH) 24, 48, and 72, the cell survival rate was detected by cell counting kit 8 and the cytotoxicity was graded (n=5). The erythrocytes of a 6-week-old male Sprague-Dawley male rat were divided into normal saline group, ultra-pure water group, and 5 mg/mL ADM extract group, 10 mg/mL ADM extract group, and 15 mg/mL ADM extract group which were treated with the corresponding final concentrations of porcine ADM extract respectively. After reaction for 3 h, the absorbance value of hemoglobin was detected by microplate reader to represent the blood compatibility of porcine ADM (n=3). ESCs were isolated and cultured from the discarded prepuce of a 6-year-old healthy boy who was treated in the Department of Urology of the First Affiliated Hospital of Army Medical University (the Third Military Medical University) in July 2020, and then identified by flow cytometry. The porcine ADM particles of composite ESC (hereinafter referred to as ESC/ADM) were constructed by mixed culture. After 3 days of culture, the composite effect of ESC/ADM was observed by HE staining and laser scanning confocal microscope. Thirty-six 7-8-week-old male non-thymic nude mice were divided into phosphate buffer solution (PBS) alone group, ADM alone group, ESC alone group, and ESC/ADM group, with 9 mice in each group, and the wound model of full-thickness skin defect was established. Immediately after injury, the wounds were treated with the corresponding reagents at one time. On post injury day (PID) 1, 7, 11, and 15, the wound healing was observed and the wound healing rate was counted (n=3). On PID 7, the epithelialization of wounds was observed by HE staining and the length of un-epithelialized wound was measured (with this and the following sample numbers of 4). On PID 11, the dermal area and collagen deposition of wounds were observed by Masson staining and the dermal area of wound section was calculated, the number of cells expressing CD49f, a specific marker of ESC, was calculated with immunofluorescence staining, the mRNA expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in ESC after wound transplantation was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Data were statistically analyzed with independent sample t test, one-way analysis of variance, analysis of variance for repeated measurement, and least significant difference t test. Results: The porcine ADM was white particles and composed of reticular structure, with no cells inside, disordered structure, and rough surface. The absorption peak of porcine ADM appeared at the wave numbers of 1 659, 1 549, and 1 239 cm-1, respectively. The main particle size distribution of porcine ADM in solution was 500 to 700 nm, with negative charge on the surface. The morphology of porcine ADM in static state at 30 min and on 1 and 5 d was relatively stable. The water absorption of porcine ADM remained relatively high level in static state from 30 min to 120 min. The cytotoxicity of mouse embryonic Fbs in 6.5 g/L ADM extract group, 12.5 g/L ADM extract group, and 25.0 g/L ADM extract group was grade 1 at PCH 24, and the cytotoxicity of the other groups was 0 grade at each time point. After reaction for 3 h, the absorbance value of hemoglobin of erythrocytes in ultra-pure water group was significantly higher than the values in normal saline group and 15 mg/mL ADM extract group (with t values of 8.14 and 7.96, respectively, P<0.01). After 3 days of culture, the cells of the fourth passage showed pebble-like morphology, with low expression of CD71 and high expression of CD49f, which were identified as ESCs. There was ESC attachment and growth on porcine ADM particles. On PID 1, the wound sizes of nude mice were almost the same in PBS alone group, ADM alone group, ESC alone group, and ESC/ADM group. On PID 7, 11, and 15, the wound contraction of nude mice in each group was observed, especially in ADM alone group, ESC alone group, and ESC/ADM group. On PID 7, the wound healing rates of nude mice in ESC alone group and ESC/ADM group were significantly higher than the rate in PBS alone group (with t values of 2.83 and 4.72 respectively, P<0.05 or P<0.01). On PID 11, the wound healing rate of nude mice in ESC/ADM group was significantly higher than that in PBS alone group (t=4.86, P<0.01). On PID 15, the wound healing rates of nude mice in ADM alone group, ESC alone group, and ESC/ADM group were significantly higher than the rate in PBS alone group (with t values of 2.71, 2.90, and 3.23 respectively, P<0.05). On PID 7, the length of un-epithelialized wound of nude mice in ADM alone group, ESC alone group, and ESC/ADM group was (816±85), (635±66), and (163±32) μm, respectively, which were significantly shorter than (1 199±43) μm in PBS alone group (with t values of 5.69, 10.19, and 27.54 respectively, P<0.01). On PID 11, the dermal areas of wound section of nude mice in ADM alone group, ESC alone group, and ESC/ADM group were significantly larger than the area in PBS alone group (with t values of 27.14, 5.29, and 15.90 respectively, P<0.01); the collagen production of nude mice in ADM alone group and ESC/ADM group was more obvious than that in PBS alone group, and the collagen production of nude mice in ESC alone group and PBS alone group was similar. On PID 11, in the wounds of nude mice in ESC alone group and ESC/ADM group, the cells with positive expression of CD49f were respectively 135±7 and 185±15, and the mRNA expressions of GAPDH were positive; while there were no expressions of CD49f nor mRNA of GAPDH in the wounds of nude mice in PBS alone group and ADM alone group. Conclusions: ESC/ADM particles can promote the wound healing of full-thickness skin defects in nude mice, which may be related to the improved survival rate of ESCs after transplantation and the promotion of dermal structure rearrangement and angiogenesis by ADM.

Determination of acetochlor and its metabolites in urine using liquid chromatography-tandem mass spectrometry / 中华劳动卫生职业病杂志

Objective: A method for the determination of acetochlor and its metabolites in urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established. Methods: After cleaned-up by a HLB extraction cartridges, the urine was eluted with 1% acetic acid acetonitrile solution. The target compounds were separated by ACQUITY UPLC®HSS T3 Column (2.1 mm×100 mm×1.8 μm) by using 1% formic acid solution and acetonitrile as mobile phase with gradient elution program, and analyzed in positive electrospray ionization mode by liquid chromatography tandem mass spectrometry. Results: All the target compounds showed good linear relationships in the range of 1-50 μg/L, and the correlation coefficients (r) were higher than 0.997. The recoveries rates at three different spiked levels for all target compounds in blank matrices were 107.6%-129.1%, and the relative standard deviations (RSD) were 1.5%-9.9% (n=6) . The limits of detection and quantitation of the method were 0.04-0.11 μg/L and 0.15-0.42 μg/L, respectively, and target substances were detected in all urine samples from occupational exposure workers to acetochlor. Conclusion: This method is suitable for rapid screening and analysis of acetochlor and metabolites in urine with the advantages of accuracy, rapidity, simplicity, high sensitivity and good specificity.

Causes and countermeasures of the rapidly rising burden on cervical cancer in Chinese women / 中华流行病学杂志

The world is entering a new era of accelerated elimination of cervical cancer, while the age-standardized incidence, and mortality of cervical cancer in China are rising rapidly. This article summarizes and describes the current situation and trends of the burden of cervical cancer in China, reviews and analyzes the comprehensive prevention practice of cervical cancer, focusing on critical reasons for the increasing burden of cervical cancer, from the perspectives of sociology, behavior, and epidemiology in the population. Countermeasures are proposed to provide guidance and theoretical reference for the precise prevention of cervical cancer to eliminate cervical cancer.

Summary of tools for assessment of public health emergency response capability / 中华流行病学杂志

With the progress of globalization, the public health emergencies represented by major infectious diseases have become a major challenge for the public health management in China. The article briefly describes the emergency response capability assessment tools in China, and introduces two emergency response assessment tools with complete content structure and wide application in the world. Then the advantages and disadvantages of the tools are compared and discussed in order to provide reference for improvement of the assessment tools for public health emergency response capability in China.

Protocol-optimizing study of combining Tuina and horse-riding squat exercise for knee osteoarthritis / 针灸推拿医学（英文版）

Objective: To evaluate the efficacy of Tuina (Chinese therapeutic massage) manipulation plus horse-riding squat exercise in treating knee osteoarthritis (KOA) and optimize the combining protocol. Methods: Based on a 2×2 factorial design, 120 eligible KOA patients were randomized into a manipulation group (group A1B2), a manipulation plus horse-riding squat group (group A1B1), a sitting knee-adjustment group (group A2B2 group), and a sitting knee-adjustment plus horse-riding squat group (group A2B1), with 30 cases in each group. The intervention was conducted three times a week, lasting for four weeks. The Western Ontario and McMaster Universities osteoarthritis index (WOMAC) was taken as the major measure for efficacy evaluation (including three component scores, pain, stiffness, and daily function, and total score). Results: The three component scores (pain, stiffness, and daily function) and the total score of WOMAC showed significant differences after the intervention in the four groups (P<0.05). There were significant inter-group differences in the WOMAC stiffness score amongst the four groups after the intervention (P<0.05). In group A1B1, the step length, stride, walking speed, and knee joint flexion angle changed significantly after treatment (P<0.05). After the intervention, the step length changed significantly in group A1B2 (P<0.05), and the walking speed changed significantly in group A2B1 (P<0.05). There were no significant differences in the step length, stride, walking speed, or knee joint flexion angle among the four groups (P>0.05). The extensor peak torque at 180 °/s changed significantly in group A1B2 after treatment (P<0.05). Neither the intra-group nor the inter-group comparisons of the four groups revealed significant differences in the other isokinetic muscle strength parameters (P>0.05). The main effect of manipulation showed significant in affecting the WOMAC pain and total scores (P<0.05). The main effect of horse-riding squat exercise showed significant in affecting the WOMAC pain and stiffness scores (P<0.05). Conclusion: The four treatment protocols all can improve the symptoms of KOA, for instance, relieving pain and stiffness, and enhancing daily function. Group A2B1 produces the most eminent effect in relieving joint stiffness. The main effects of both manipulation and horse-riding squat exercise are significant in reducing pain. Besides, the main effect of horse-riding squat exercise is significant in relieving joint stiffness.

Establish a diagnosis differential model for IgA nephropathy and non-IgA nephropathy by machine learning / 中华检验医学杂志

Objective:To establish a differential diagnosis model for IgA nephropathy and non-IgA nephropathy based on machine learning algorithms.Methods:Retrospective study adopted,from 2019 to 2020,260 patients were referred to the Department of Nephrology at the First Affiliated Hospital of Kunming Medical University, the First People′s Hospital in Yunnan province, and Yan′an Hospital of Kunming city. All patients were diagnosed by renal pathology, 130 cases of primary IgA nephropathy, the 130 cases of non-IgA nephropathy. Collection of materials, including gender and age, 28 clinical data, and routine laboratory test results,the sex ratio of IgA nephropathy group and non-IgA nephropathy group were 59∶71 and 64∶66 respectively, the ages were 37.20 (21.89, 53.78) and 43.30 (27.77, 59.18) years, respectively. 260 patients were divided into a training set (70%, 182 cases) and a test set (30%, 78 cases). Using the decision tree, random forests, support vector machine, extreme gradient boosting to establish a differential diagnosis model for IgA nephropathy and non-IgA nephropathy. Based on the true positive rate, true negative rate, false-positive rate, false-negative rate, accuracy, subjects features work area under the curve(AUC), the precision ratio, recall ratio, and F1 score, comprehensively evaluate the performance of each model, finally, the best performance of the model was chosen. Using SPSS 25.0 to analyze the data, P<0.05 was considered to be statistically significant. Results:The accuracy of the decision tree, support vector machine, random forests and extreme gradient boosting establish differential diagnosis model was 67.95%, 70.51%, 80.77% and 83.33%, respectively; AUC values was 0.74, 0.76, 0.80 and 0.83; Judgment for primary IgA nephropathy F1 score was 0.73, 0.72, 0.80 and 0.83, respectively. The efficiency of the extreme gradient boosting model based on the above evaluation indicators is the highest, its diagnosis of IgA nephropathy of the sensitivity and specificity respectively 89% and 79%. The variable importance from high to low was blood albumin, IgA/C3, serum creatinine, age, urine protein, urine albumin, high-density lipoprotein cholesterol, urea.Conclusion:The differential diagnosis model for IgA nephropathy was established successfully and non-IgA nephropathy and the efficiency performance of the extreme gradient boosting algorithm was the best.

Sleeve gastrectomy and simultaneous repair of hiatal hernia for prevention of gastroesophageal reflux / 中华普通外科杂志

Objective:To evaluate the laparoscopic sleeve gastrectomy combined with hiatal hernia repair surgery for weight loss and antireflux.Methods:This study included 21 obese patients with gastroesophageal reflux who underwent laparoscopic sleeve gastrectomy at the Weight Loss Metabolism Center of the Department of Hepatobiliary and Pancreatic Surgery of Zhejiang Provincial People's Hospital from Dec 2019 to Dec 2020. Patients were divided into simple bariatric surgery group (9 cases) and simultaneous combined surgery group (12 cases).Results:In the combined surgery group, 1 case had postoperative gastric leakage. The postoperative body weight, waist circumference, and BMI indexes of the two groups showed a downward trend ( F=5.154, P=0.013; F=14.319, P<0.001; F=6.725, P=0.004). There was a statistically significant difference in the excess weight loss in both the two groups at 6 months after the operation compared to 1 month after the operation ( t=8.927, P<0.001; t=8.926, P<0.001). There was no statistically significant difference in postoperative lower esophageal sphincter resting pressure and Gerd symptom score in the bariatric surgery group compared with preoperative ( t=-0.891, P=0.507; t=0.629, P=0.298). The postoperative Gerd symptom score of the patients in the combined surgery group was significantly lower than that before the operation, and the resting pressure of the lower esophageal sphincter was significantly higher than that before the operation, ( t=-10.539, P<0.001; t=5.066, P=0.038). Conclusion:Combined surgery have the same weight loss effect as in simple bariatric surgery in obese patients with gastroesophageal reflux, in addition to stronger anti-reflux effect.

PI3K/Akt/mTOR signaling pathway in cutaneous squamous cell carcinoma / 中华皮肤科杂志

The pathogenesis of cutaneous squamous cell carcinoma (cSCC) is complicated, and treatment methods of advanced cSCC remain insufficient. This review summarizes the role of phosphatidylinositol 3-kinase (PI3K) /protein kinase B (Akt) /mammalian target of rapamycin (mTOR) signaling pathway in the pathogenesis of cSCC, as well as progress in the treatment of cSCC targeting this pathway, and provides new ideas for targeted therapy of cSCC.

Clinicopathological and immunophenotypic analysis of 24 cases of transformed mycosis fungoides / 中华皮肤科杂志

Objective:To investigate clinicopathological features and prognosis of transformed mycosis fungoides (TMF) .Methods:A retrospective analysis was performed on clinicopathological data collected from 24 patients with TMF, as well as on flow cytometry results of 16 peripheral blood samples obtained from 11 of the 24 patients, who visited Hospital of Dermatology, Chinese Academy of Medical Sciences between 2014 and 2020.Results:Among the 24 patients, 11 were males and 13 were females. Their average age at diagnosis of TMF was 50.0 years (range: 18 - 77 years), and patients with early-stage TMF (9 cases) and tumor-stage TMF (15 cases) were aged 44.8 and 52.6 years on average, respectively. The average time interval from diagnosis of MF to large cell transformation was 3.7 years, and 8 patients were diagnosed with TMF at the initial visit. Histopathologically, large cells infiltrated in a diffuse pattern in 20 cases, as well as in a multifocal pattern in 4, and the proportion of large cells in 7 cases was greater than 75%. Immunohistochemically, 18 patients showed positive staining for CD30, and the proportion of CD30-positive large cells was greater than 75% in 9; negative staining for CD30 was observed in 6. Flow cytometry of 16 peripheral blood samples showed the presence of cell subsets expressing clonal T cell receptor (TCR) -vβ in 2 of 4 patients with early-stage TMF and 10 of 12 with tumor-stage TMF, and tumor cells with higher forward scatter than normal lymphocytes were detected in 16 samples. During the follow-up, among the patients with early-stage TMF, 3 progressed to tumor-stage TMF 3.3 years on average after large cell transformation, 1 progressed to erythrodermic MF in stage IIIA, and the other 4 still showed an indolent course; among the patients with tumor-stage TMF, 1 progressed to stage-IV TMF, and 5 died 3.3 (1.5 - 6) years after large cell transformation.Conclusion:Large cell transformation may occur in patients with MF in any stage, some patients have poor prognosis, so close follow-up is needed for patients with TMF.

Clinicopathological analysis and literature review of Burkitt-like lymphoma with 11q aberration / 中国综合临床

Objective:To investigate the clinicopathological features,differential diagnosis,treatment and prognosis of Burkitt-like lymphoma with 11q aberration (BLL-11q).Methods:The clinical manifestations,histological morphology,immunophenotype and molecular genetic changes of 2 cases of BLL-11q admitted to the department of pathology of The First People's Hospital of Lianyungang in 2020 and 2021 were analyzed retrospectively,and the relevant literatures were reviewed.Results:Patients were found with right neck masses inadvertently and grew rapidly. They presented with localized disease with Ann Arbor stages IA and IIA. Microscopically, the normal structure of the lymph node disappeared and was replaced by a diffuse proliferation of lymphocytes, with consistent morphology and medium size. And the presence of "star-sky" phenomenon was obvious, the morphological characteristics were similar to Burkitt lymphoma. Immunophenotypically, tumor cells were diffusely positive for CD20, CD79α, PAX5, CD10 and Bcl-6, partly moderately positive for C-MYC and MUM-1, however, CD3, Bcl-2, CD30 and TDT were negative,Ki-67 positive index was more than 95%, and EBER was negative. FISH detection showed that MYC, Bcl-2, and Bcl-6 were negative. Both cases had the 11q23.3 gain and 11q24.3 loss. Both patients were treated with chemotherapy and followed up for 10-22 months,and achieved complete remission and disease-free survival.Conclusion:BLL-11q is a rare germinal center B-cell lymphoma with abnormal long arm of chromosome 11 and lack of MYC gene rearrangement. It should be distinguished from Burkitt lymphoma, diffuse large B-cell lymphoma, B-lymphoblastic lymphoma, large B-cell lymphoma with IRF4 rearrangement and high-grade B-cell lymphoma. On the basis of morphology and immunophenotype, the diagnosis depends on genetic detection. There may be a better prognosis.

The 10-year outcome and prognostic factors of laparoscopic D 2 radical distal gastrectomy for locally advanced gastric cancer: a CLASS multicenter study / 中华消化外科杂志

Objective:To investigate the 10-year outcome and prognostic factors of laparo-scopic D 2 radical distal gastrectomy for locally advanced gastric cancer. Methods:The retrospec-tive cohort study was conducted. The clinicopathological data of 652 patients with locally advanced gastric cancer who were admitted to 16 hospitals from the multicenter database of laparoscopic gastric cancer surgery in the Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group, including 214 cases in the First Affiliated Hospital of Army Medical University, 191 cases in Fujian Medical University Union Hospital, 52 cases in Nanfang Hospital of Southern Medical University, 49 cases in West China Hospital of Sichuan University, 43 cases in Xijing Hospital of Air Force Medical University, 25 cases in Jiangsu Province Hospital of Chinese Medicine, 14 cases in the First Medical Center of the Chinese PLA General Hospital, 12 cases in No.989 Hospital of PLA, 12 cases in the Third Affiliated Hospital of Sun Yat-Sen University, 10 cases in the First Affiliated Hospital of Nanchang University, 9 cases in the First People's Hospital of Foshan, 7 cases in Zhujiang Hospital of Southern Medical University, 7 cases in Fujian Medical University Cancer Hospital, 3 cases in Zhongshan Hospital of Fudan University, 2 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 2 cases in Peking University Cancer Hospital & Institute, from February 2004 to December 2010 were collected. There were 442 males and 210 females, aged (57±12)years. All patients underwent laparoscopic D 2 radical distal gastrectomy. Observation indicators: (1) surgical situations; (2) postoperative pathological examination; (3) postoperative recovery and complications; (4) follow-up; (5) prognostic factors analysis. Follow-up was conducted by outpatient examination and telephone interview to detect the tumor recurrence and metastasis, postoperative survival of patients up to March 2020. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers or percen-tages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was analyzed using the rank sum test. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-Rank test was used for survival analysis. Univariate and multivariate analyses were analyzed using the COX hazard regression model. Results:(1) Surgical situations: among 652 patients, 617 cases underwent D 2 lymph node dissection and 35 cases underwent D 2+ lymph node dissection. There were 348 cases with Billroth Ⅱ anastomosis, 218 cases with Billroth Ⅰ anastomosis, 25 cases with Roux-en-Y anastomosis and 61 cases with other digestive tract reconstruction methods. Twelve patients had combined visceral resection. There were 569 patients with intraoperative blood transfusion and 83 cases without blood transfusion. The operation time of 652 patients was 187(155,240)minutes and volume of intraoperative blood loss was 100(50,150)mL. (2) Postoperative pathological examina-tion: the maximum diameter of tumor was (4.5±2.0)cm of 652 patients. The number of lymph node dissected of 652 patients was 26(19,35), in which the number of lymph node dissected was >15 of 570 cases and ≤15 of 82 cases. The number of metastatic lymph node was 4(1,9). The proximal tumor margin was (4.8±1.6)cm and the distal tumor margin was (4.5±1.5)cm. Among 652 patients, 255 cases were classified as Borrmann type Ⅰ-Ⅱ, 334 cases were classified as Borrmann type Ⅲ-Ⅳ, and 63 cases had missing Borrmann classification data. The degree of tumor differentiation was high or medium in 171 cases, low or undifferentiated in 430 cases, and the tumor differentiation data was missing in 51 cases. There were 123, 253 and 276 cases in pathological stage T2, T3 and T4a, respectively. There were 116, 131, 214 and 191 cases in pathological stage N0, N1, N2 and N3, respectively. There were 260 and 392 cases in pathological TNM stage Ⅱ and Ⅲ, respectively. (3) Postoperative recovery and complications: the time to postoperative first out-of-bed activities, time to postoperative first flatus, time to the initial liquid food intake, duration of postoperative hospital stay of 652 patients were 3(2,4)days, 4(3,5)days, 5(4,6)days, 10(9,13)days, respectively. Among 652 patients, 69 cases had postoperative complications. Clavien-Dindo grade Ⅰ-Ⅱ, grade Ⅲa, grade Ⅲb, and grade Ⅳa complications occurred in 60, 3, 5 and 1 cases, respectively (some patients could have multiple complications). The duodenal stump leakage was the most common surgical complication, with the incidence of 3.07%(20/652). Respiratory complication was the most common systemic complication, with the incidence of 2.91%(19/652). All the 69 patients were recovered and discharged successfully after treatment. (4) Follow-up: 652 patients were followed up for 110-193 months, with a median follow-up time of 124 months. There were 298 cases with postoperative recurrence and metastasis. Of the 255 patients with the time to postoperative recurrence and metastasis ≤5 years, there were 21 cases with distant metastasis, 69 cases with peritoneal metastasis, 37 cases with local recurrence, 52 cases with multiple recurrence and metastasis, 76 cases with recurrence and metastasis at other locations. The above indicators were 5, 9, 10, 4, 15 of the 43 patients with the time to postoperative recurrence and metastasis >5 years. There was no significant difference in the type of recurrence and metastasis between them ( χ2=5.52, P>0.05). Cases in pathological TNM stage Ⅱ and Ⅲ were 62 and 193 of the patients with the time to postoperative recurrence and metastasis ≤5 years, versus 23 and 20 of the patients with the time to postoperative recurrence and metastasis >5 years, showing a significant difference in pathological TNM staging between them ( χ2=15.36, P<0.05). Cases in pathological stage T2, T3, T4a were 42, 95, 118 of the patients with the time to postoperative recurrence and metastasis ≤5 years, versus 9, 21, 13 of the patients with the time to postoperative recurrence and metastasis >5 years, showing no significant difference in pathological T staging between them ( Z=-1.80, P>0.05). Further analysis showed no significant difference in cases in pathological stage T2 or T3 ( χ2=0.52, 2.08, P>0.05) but a significant difference in cases in pathological stage T4a between them ( χ2=3.84, P<0.05). Cases in pathological stage N0, N1, N2, N3 were 19, 44, 85, 107 of the patients with the time to postoperative recurrence and metastasis ≤5 years, versus 12, 5, 18, 8 of the patients with the time to postoperative recurrence and metastasis >5 years, showing a significant difference in pathological N staging between them ( Z=-3.34, P<0.05). Further analysis showed significant differences in cases in pathological stage N0 and N3 ( χ2=16.52, 8.47, P<0.05) but no significant difference in cases in pathological stage N1 or N2 ( χ2=0.85, 1.18, P>0.05). The median overall survival time was 81 months after surgery and 10-year overall survival rate was 46.1% of 652 patients. The 10-year overall survival rates of patients in TNM stage Ⅱ and Ⅲ were 59.6% and 37.5%, respectively, showing a significant difference between them ( χ2=35.29, P<0.05). In further analysis, the 10-year overall survival rates of patients in pathological TNM stage ⅡA, ⅡB, ⅢA, ⅢB and ⅢC were 65.6%, 55.8%, 46.9%, 37.1% and 24.0%, respectively, showing a significant difference between them ( χ2=55.06, P<0.05). The 10-year overall survival rates of patients in patholo-gical stage T2, T3 and T4a were 55.2%, 46.5% and 41.5%, respectively, showing a significant difference between them ( χ2=8.39, P<0.05). The 10-year overall survival rates of patients in patholo-gical stage N0, N1, N2 and N3 were 63.7%, 56.2%, 48.5% and 26.4%, respectively, showing a signifi-cant difference between them ( χ2=54.89, P<0.05). (5) Prognostic factors analysis: results of univariate analysis showed that age, maximum diameter of tumor, degree of tumor differentiation as low or undifferentiated, pathological TNM staging, pathological T staging, pathological stage N2 or N3, post-operative chemotherapy were related factors for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparoscopic D 2 radical distal gastrectomy ( hazard ratio=1.45, 1.64, 1.37, 2.05, 1.30, 1.68, 3.08, 0.56, 95% confidence interval as 1.15-1.84, 1.32-2.03, 1.05-1.77, 1.62-2.59, 1.05-1.61, 1.17-2.42, 2.15-4.41, 0.44-0.70, P<0.05). Results of multivariate analysis showed that maximum diameter of tumor >4 cm, low-differentiated or undifferentiated tumor, pathological TNM stage Ⅲ were independent risk factors for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparoscopic D 2 radical distal gastrectomy ( hazard ratio=1.48,1.44, 1.81, 95% confidence interval as 1.19-1.84, 1.11-1.88, 1.42-2.30, P<0.05) and postoperative chemotherapy was a independent protective factor for the 10-year overall survi-val rate of locally advanced gastric cancer patients undergoing laparoscopic D 2 radical distal gastrec-tomy ( hazard ratio=0.57, 95% confidence interval as 045-0.73, P<0.05). Conclusions:Laparoscopic assisted D 2 radical distal gastrectomy for locally advanced gastric cancer has satisfactory 10-year oncologic outcomes. A high proportion of patients in pathological TNM stage Ⅲ, pathological stage T4a, pathological stage N3 have the time to postoperative recurrence and metastasis ≤5 years, whereas a high proportion of patients in pathological TNM stage Ⅱ or pathological stage N0 have the time to postoperative recurrence and metastasis >5 years. Maximum diameter of tumor >4 cm, low-differentiated or undifferentiated tumor, pathological TNM stage Ⅲ are independent risk factors for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparos-copic D 2 radical distal gastrectomy. Postoperative chemotherapy is a independent protective factor for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparos-copic D 2 radical distal gastrectomy.

Application value of Overlap guiding tube in Overlap esophagojejunostomy of laparoscopic total gastrectomy / 中华消化外科杂志

Objective:To investigate the application value of Overlap guiding tube (OGT) in Overlap esophagojejunostomy of laparoscopic total gastrectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients with gastric cancer who were admitted to Nanfang Hospital of Southern Medical University from June to July in 2021 were collected. There were 3 males and 2 females, aged from 48 to 61 years, with a median age of 54 years. Patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination and telephone interview to detect postoperative anastomotic stenosis and esophageal reflux up to September 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR) or M(range). Count data were represented as absolute numbers. Results:(1) Surgical situations: 5 patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy and D 2 lymph node dissection success-fully, achieving R 0 resection. There was no combined organ resection, intraoperative conversion to laparotomy or combined thoracotomy. There was no intraoperative conversion to other esophagoje-junostomy method either. The tumor diameter, length of surgical incision, the number of lymph nodes dissected, time of esophagojejunal anastomosis, time of digestive reconstruction, operation time, volume of intraoperative blood loss of 5 patients were 3.0(2.8)cm, 5.0(2.0)cm, 47.0(21.0), 21.0(5.0)minutes, 62.0(23.0)minutes, 295.0(75.0)minutes, and 50.0(60.0)mL, respectively. The anvil fork of linear stapler was successfully inserted into esophageal lumen by once operation in 4 cases of 5 patients and by twice operation in 1 case to complete the esophagojejunostomy. (2) Post-operative situations: the time to first out-of-bed activities, time to postoperative first anal flatus, time to postoperative initial liquid diet intake, time to postoperative initial semi-liquid diet intake, time to abdominal drainage tube removal, duration of postoperative hospital stay of 5 patients were 2.0(1.0)days, 3.0(2.0)days, 4.0(3.0)days, 6.0(3.0)days, 7.0(4.0)days, and 9.0(6.0)days, respectively. Results of postoperative pathological examination of 5 patients showed gastric adenocar-cinoma in all the 5 patients, with the TNM staging as stage pT2-4aN0M0. The esophageal surgical margin was negative in all cases, and the length of proximal margin from esophagus was 5.0(4.0)cm. None of the 5 patients developed anastomotic leakage, anastomotic bleeding or anastomotic stenosis. Two cases with mild pneumonia (Clavien-Dindo grade Ⅱ) were cured by conservative treatment such as anti-infection and expectoration promotion. There was no unplanned secondary surgery or perioperative death occurred to the 5 patients. (3) Follow-up: 5 patients were followed up for 3 months. None of the 5 patients developed anastomotic stenosis or esophageal reflux during the follow-up. Conclusion:OGT-assisted Overlap esophagojejunostomy of laparoscopic total gas-trectomy is safe and feasible, with good short-term effects.

Analysis of the effect of inter-spinal distraction fusion and fixation combined with limited decompression on the treatment of lumbar spinal stenosis in elderly patients / 国际外科学杂志

Objective:To analyze the effect of inter-spinal distraction fusion and fixation (ISDFF) combined with limited decompression on the treatment of lumbar spinal stenosis in elderly patients.Methods:A total of 32 elderly patients with lumbar spinal stenosis, aged from 80 to 87 years old (mean age: 82.0±2.0 years) including 10 males and 22 females, in the Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University from January 2016 to January 2020 were enrolled in this retrospective study. Clinical evaluation and imaging measurement were performed before operation, after operation, 6 months and 24 months after operation. SPSS software was used for statistical analysis. Measured data of normal distribution were expressed as means±standard deviation. One way analysis of variance was used for comparison between groups. Paired t-test was used to compare between preoperative and postoperative as well as between preoperative and 24 months′ follow-up. Results:All of the 32 patients had one or more common accompanying diseases, such as hypertension, diabetes, coronary heart disease, and so on. All patients were successfully completed the operation with a total of 32 segments. VAS score was decreased from (6.22±0.91) before operation to (1.94±0.76) at 24 months( t=16.52, P<0.001). ODI score was also demonstrated the similar trend, from (54.17±10.65) preoperatively to (19.91±4.20) at 24 months follow-up( t=15.89, P<0.001). JOA score was significantly increased from (11.69±3.36) before surgery to (23.44±1.66) at the last follow-up ( t=-19.90, P<0.001). In the change of imaging, the intervertebral angle was decreased from preoperation (9.12±4.65) to (6.77±2.70) at 24 months( t=3.53, P=0.001). The posterior disk height was increased from (0.68±0.19) cm to (0.76±0.19) cm at the last follow-up( t=-2.45, P=0.020). Conclusions:As a new type of minimally invasive internal fixator, the ISDFF combined with limited decompression can relieve the pain of elderly patients with lumbar spinal stenosis and improve the quality of life. It is suitable for the treatment of elderly patients with lumbar spinal stenosis.

Hygienic economic evaluation of inter-spinal distraction fusion and fixation for lumbar disc herniation / 国际外科学杂志

Objective:To analyze the clinical efficacy of inter-spinal distraction fusion and fixation and Posterior lumbar interbody fusion in the treatment of lumbar disc herniation with stenosis, and to evaluate the health economics of the two surgical methods.Methods:Retrospectivly analyzed the clinical data of 400 patients with lumbar disc herniation with stenosis, who were enrolled in Beijing Friendship Hospital, Capital Medical University from Jan. 2015 to Jan. 2019, including 190 male cases and 210 female cases, aged from 50 to 87 years old, with the average age of 67.97. All patients were divided into two groups according to different surgical methods. Among them, 200 patients used interspinous process fusion and distraction fixation (ISDFF group), the other 200 cases used posterior lumbar decompression and pedicle internal fixation (PLIF group). All patients completed the follow-up time of more than 1 year after operation. The basic information of patients′ age, gender, total number of days in hospital, intraoperative bleeding, operation time, surgical incision length and other basic information were observed. The Oswestry dysfunction index (ODI), the Japanese Orthopaedic Association Score (JOA) and the visual analog scale (VAS) were used to evaluate the relief of symptoms before and after the two groups of patients. Total medical expenses, anesthesia expenses, surgical expenses and other expenses were analysed. The software of SPSS 20.0 were conducted to analyze data.Results:The patients in the ISDFF group were (70.84±8.93) years old, and the PLIF group was (65.10±10.23) years old ( t=5.98, P=0.008). The operation time in the ISDFF group was (59.21±16.22) min, and the operation time in the PLIF group was (81.31±17.24) min( t=13.20, P<0.001). The bleeding volume of the ISDFF group was (33.24±11.31) mL, and the bleeding volume of the PLIF group was (67.30±17.61) mL ( t=23.02, P<0.001). The length of the surgical incision in the ISDFF group was (8.27±2.53) cm, and the length of the surgical incision in the PLIF group was (11.15±1.91) cm ( t=11.848, P<0.001). The total hospitalization time in the ISDFF group was (15.15±0.54) days, and the total hospitalization time in the PLIF group was (19.86±0.97) days( t=4.26, P<0.001). There was no significant difference in preoperative ODI, JOA and VAS between the two groups ( P>0.05). Symptoms of postoperative patients were significantly improved compared with preoperative. There were statistical differences in ODI, JOA and VAS between the two groups before and after operation ( P<0.05). However, ODI, JOA and VAS were no statistical difference between the two groups after operation. Complications occurred in 5 cases of the two groups of patients, including two cases of superficial infection in the PLIF group, two cases of dural tear in the PLIF group, one case of spinous process fracture in the ISDFF group. The total hospitalization fee for ISDFF was (57 450±8 670) (yuan), and the total hospitalization fee for PLIF was (75 770±1 640) (yuan), with statistical differences ( t=9.92, P<0.001). The cost of ISDFF operation was 1864±38.19 (yuan), and the cost of PLIF operation was 2352±41.39 (yuan) ( t=8.65, P<0.001). ISDFF antibacterial drug usage fee was 635.5±64.69 (yuan), PLIF antibacterial drug usage fee was 1449±307.1 (yuan) ( t=2.59, P<0.001). The one-time medical material cost during the ISDFF operation was (38 990±300) (yuan), and the one-time medical material cost during the PLIF operation was (52 110±150) (yuan) ( t=5.88, P<0.001). The excellent and good rate of ISDFF group was 92%, and that of PLIF group was 86%. In this study, the total cost of hospitalization was used as an indicator to measure the cost, and further cost-effectiveness evaluation was made. For every good patient, the cost of the ISDFF group was 62 450 yuan, and the cost of the PLIF group was 88, 100 yuan. Conclusions:ISDFF is beneficial to reduce the cost of medical insurance in China, which is in line with the direction of national reform to reduce medical expenditure. It is a surgical method worthy of wide promotion and has a good application prospect.

Clinical characteristics and risk factors of neonatal adrenal hemorrhage / 国际儿科学杂志

Objective:To explore the clinical characteristics and risk factors of neonatal adrenal hemorrhage(NAH), and to improve the understanding, diagnosis and treatment of this disease.Methods:In this study, a retrospective nested case-control study was used to collect clinical data of neonates diagnosed with NAH from January 2011 to December 2021 in the Department of Neonatology, Shengjing Hospital of China Medical University, and telephone follow-up were conducted for them.NAH infants with manifestations of neonatal hyperbilirubinemia were selected as the case group, and the random number table method was used to select the neonatal hyperbilirubinemia infants with NAH excluded by imaging in the same period at a ratio of 1: 2 as the control group.Characteristics of the clinical data of the two groups were compared and analyzed by Logistic regression to explore the risk factors of NAH.Results:During the study period, a total of 31 cases of NAH were diagnosed, with an average gestational age of(37.6±2.2) weeks, including 19 males, 25 full-term infants, 6 cases with macrosomia, 30 cases with natural labor, 29 cases with hyperbilirubinemia, 8 cases with birth injury, 7 cases with asphyxia, 9 cases with bilirubin encephalopathy, 12 cases with sepsis, 13 cases with intracranial hemorrhage, 17 cases with anemia, 9 cases with respiratory disease, 5 cases with hyperkalemia, 6 cases with hyponatremia.The results of NAH ultrasonography showed that 8 cases of hematoma had medium and low echoes, 6 cases of mixed echoes, and 17 cases of liquid flocculent echoes with or without punctate echoes.Color Doppler flow imaging results showed no blood flow signal.There were 26 cases on the right side, 4 cases on the left side, and 1 case on both sides.A total of 26 cases were followed up.Ultrasonography showed that most haematomas were absorbed within 1 to 3 months and disappeared within 6 months.Twenty-nine cases were included in the case group and 58 cases in the control group.Univariate analysis showed that age, birth weight, macrosomia, mode of delivery, bilirubin encephalopathy, neonatal sepsis, abdominal distension, anemia, asphyxia, total bilirubin, indirect bilirubin, Hb and CRP were significantly higher than those in the control group( P<0.05). Multivariate logistic regression analysis showed that macrosomia( OR=7.415, 95% CI=1.342~40.956, P=0.022) and asphyxia( OR=12.075, 95% CI=1.293~112.736, P=0.029) were independent risk factors of NAH. Conclusion:NAH is common in naturally born full-term infants, with a lack of specific clinical manifestations.Unexplained persistent hyperbilirubinemia may be its first symptom, often accompanied by anemia and ion disturbance.A few infants may have adrenal insufficiency.Macrosomia and asphyxia may be the risk factors for the occurrence of NAH.

A targeted covalent inhibitor of p97 with proteome-wide selectivity

A resurging interest in targeted covalent inhibitors (TCIs) focus on compounds capable of irreversibly reacting with nucleophilic amino acids in a druggable target. p97 is an emerging protein target for cancer therapy, viral infections and neurodegenerative diseases. Extensive efforts were devoted to the development of p97 inhibitors. The most promising inhibitor of p97 was in phase 1 clinical trials, but failed due to the off-target-induced toxicity, suggesting the selective inhibitors of p97 are highly needed. We report herein a new type of TCIs (i.e., FL-18) that showed proteome-wide selectivity towards p97. Equipped with a Michael acceptor and a basic imidazole, FL-18 showed potent inhibition towards U87MG tumor cells, and in proteome-wide profiling, selectively modified endogenous p97 as confirmed by in situ fluorescence scanning, label-free quantitative proteomics and functional validations. FL-18 selectively modified cysteine residues located within the D2 ATP site of p97. This covalent labeling of cysteine residue in p97 was verified by LC‒MS/MS-based site-mapping and site-directed mutagenesis. Further structure-activity relationship (SAR) studies with FL-18 analogs were established. Collectively, FL-18 is the first known small-molecule TCI capable of covalent engagement of p97 with proteome-wide selectivity, thus providing a promising scaffold for cancer therapy.

Ventromedial Thalamus-Projecting DCN Neurons Modulate Associative Sensorimotor Responses in Mice / 神经科学通报·英文版

The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCNVm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCNVm neurons' function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.

The Effect of Morphine On Tumor Growth of Melanoma And The Immunotherapy Efficacy / 中山大学学报(医学科学版)

ObjectiveTo study the effect of morphine on the function of CD8+ T cells， tumor growth of melanoma and immunotherapy efficacy of PD-1. MethodIsolated CD8+ T cells were activated in vitro and stimulated with different concentrations of morphine. Flow cytometry was used to analyze the percentage of activated CD8+ T cell and the secretion of IFN+. Female C57/BL6 mice were inoculated with mouse melanoma tumor cells. On day 7 after inoculation， middle dose of morphine was injected intraperitoneally and the tumor volume was recorded. The tumor growth curve and survival curve of mice were plotted. Female C57/BL6 mice were inoculated with mouse melanoma tumor cells and were intraperitoneally treated with 200ug PD-1 antibody for 3 times continuously. Meanwhile， middle dose of morphine was injected intraperitoneally and tumor volume was measured. The tumor growth curve and survival curve of the mice were plotted. ResultsCompared with control group ， middle and high doses of morphine significantly inhibited the activation of CD8+ T cells and the secretion of IFN+（P<0.05）； middle doses of morphine also promoted tumor growth （P<0.01） and shortened the survival time of tumor bearing mice. Combined treatment with PD-1 antibody， morphine significantly increased tumor growth（P<0.01） and shortened the survival time of bearing tumor mice. ConclusionsMorphine promote tumor growth and antagonize the efficacy of PD-1 immunotherapy. These effects may be related to the inhibition of morphine on the activation and function of CD8+ T cells.