Realizing Synthetic Dimensions and Artificial Magnetic Flux in a Trapped-Ion Quantum Simulator.

Synthetic dimension is a potent tool in quantum simulation of topological phases of matter. Here we propose and demonstrate a scheme to simulate an anisotropic Harper-Hofstadter model with controllable magnetic flux on a two-leg ladder using the spin and motional states of a single trapped ion. We verify the successful simulation of this model by comparing the measured dynamics with theoretical predictions under various coupling strength and magnetic flux, and we observe the chiral motion of wave packets on the ladder as evidence of the topological chiral edge modes. We develop a quench path to adiabatically prepare the ground states for varying magnetic flux and coupling strength, and we measure the chiral current on the ladder for the prepared ground states, which allows us to probe the quantum phase transition between the Meissner phase and the vortex phase. Our work demonstrates the trapped ion as a powerful quantum simulation platform for topological quantum matter.

[Investigation of the population diversity of intermediate host snails and crabs of Paragonimus along Jiulong River, Zhangjiang River and Dongxi River basins in southern Fujian Province].

OBJECTIVE: To investigate the population distribution of intermediate host snails and crabs of Paragonimus along the Jiulongjiang River, Zhangjiang River, and Dongxi River basins in Bopingling Mountain, southern Fujian Province, so as to provide baseline data for researches on parasitic disease prevention and control and enlargement of samples in the parasitic resource bank. METHODS: A total of 23 villages in 8 counties (districts) along the Jiulong River, Zhangjiang River, and Dongxi River basins in Zhangzhou City, Fujian Province were selected as survey sites during the period from November 2020 through March 2023, and snail and freshwater crabs were sampled from 1 to 3 streams and ditches neighboring residential areas in each village. Morphological identification of snails was performed according to the external morphological characteristics of collected snail shells, and the unidentified snail species sampled from the natural foci of paragonimiasis in Yunxiao County were subjected to se-quence analysis of the mitochondrial cytochrome oxidase 1 (CO1) gene. The crab species was identified by observing the morphological characteristics of the terminal segment of the first pleopod of male crabs, and Paragonimus cercariae and metacercariae were detected in collected snails. RESULTS: The shells of the unidentified snails sampled from the natural foci of paragonimiasis in Yunxiao County were approximately 50 mm in height and 18 mm in width, thick and solid, long tower cone-shaped, and had 8 to 10 whorls. CO1 gene sequence analysis identified the snail species as Sulcospira hainanensis. A total of 6 freshwater snail species belonging to 5 genera within 3 families, identified 23 survey sites, including Semisulcospira libertina, Paludomus zhangchouensis and S. hainanensis that belonged to the Family Pleurceridae, Tricula fujianensis and T. huaanensis that belonged to the subfamily Triculinae, Family Pomatiopsidae, and Melanoides tuberculata (Family Thiaridae), and 11 species of freshwater crabs belonging to 5 genera within 2 families were identified, including Sinopotamon genus of S. jianglense, S. pinheense, and S. zhangzhouense, Huananpotamon genus of H. planopodum and H. zhangzhouense, Nanhaipotamon genus of N. huaanense and N. longhaiense, and Minpotamon genus of M. nasicum and M. auritum that belonged to the Family Potamidae, and Somanniathelphusa genus of S. huaanensis and S. zhangpuensis (Family Parathelphusidae). In addition, the prevalence of P. westermani cercariae infections was 0.08% (2/2 317) in P. zhangchouensis from Danyan Village in Changtai District and 0.09% (1/1 039) in S. hainanensis from Jinkeng Village in Yunxiao County, and the prevalence of P. westermani metacercariae infections was 25.81% (8/31) in S. jianglense from Danyan Village in Changtai District, and 26.31% (5/19) in S. zhangzhouense from Jinkeng Village in Yunxiao County, respectively. CONCLUSIONS: There is a population diversity in the intermediate host snails and crabs along the Jiulongjiang River, Zhangjiang River, and Dongxi River basins in Bopingling Mountain, southern Fujian Province, and P. zhangzhouensis and S. hainanensis are, for the first time, confirmed as the first intermediate hosts of P. westermani.

Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.

BACKGROUND: Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, but their existence and relative frequency in clinical disease are unclear, as is how to target resistance. PATIENTS AND METHODS: Longitudinal mutation and methylation profiling of circulating tumour (ct)DNA was carried out in 47 patients with metastatic BRCA1-, BRCA2- or PALB2-mutant breast cancer treated with HRD-targeted therapy who developed progressive disease-18 patients had primary resistance and 29 exhibited response followed by resistance. ctDNA isolated at multiple time points in the patient treatment course (before, on-treatment and at progression) was sequenced using a novel >750-gene intron/exon targeted sequencing panel. Where available, matched tumour biopsies were whole exome and RNA sequenced and also used to assess nuclear RAD51. RESULTS: BRCA1/2 reversion mutations were present in 60% of patients and were the most prevalent form of resistance. In 10 cases, reversions were detected in ctDNA before clinical progression. Two new reversion-based mechanisms were identified: (i) intragenic BRCA1/2 deletions with intronic breakpoints; and (ii) intragenic BRCA1/2 secondary mutations that formed novel splice acceptor sites, the latter being confirmed by in vitro minigene reporter assays. When seen before commencing subsequent treatment, reversions were associated with significantly shorter time to progression. Tumours with reversions retained HRD mutational signatures but had functional homologous recombination based on RAD51 status. Although less frequent than reversions, nonreversion mechanisms [loss-of-function (LoF) mutations in TP53BP1, RIF1 or PAXIP1] were evident in patients with acquired resistance and occasionally coexisted with reversions, challenging the notion that singular resistance mechanisms emerge in each patient. CONCLUSIONS: These observations map the prevalence of candidate drivers of resistance across time in a clinical setting, information with implications for clinical management and trial design in HRD breast cancers.

[Surgical plan selection and efficacy analysis in 32 cases of laryngotracheal stenosis].

Objective: To explore the optimization of surgical procedures for laryngotracheal stenosis and its effect analysis. Methods: The data of 32 patients with acquired laryngotracheal stenosis who received surgical treatment from October 2015 to December 2021 were analyzed retrospectively. The age ranged from 19 to 72 years, with an average of (34.0±9.0) years. The medical history ranged from 1 to 32 months (median 3 months). As for etiology, there were 30 cases of iatrogenic laryngotracheal stenosis, including 20 cases of tracheal intubation and 10 cases of tracheotomy (7 cases of percutaneous tracheotomy and 3 cases of traditional tracheotomy). There were 1 case of laryngotracheal trauma and 1 case of airway Penicillium marneffei infection. According to Myer-Cotton grading system, grade Ⅳ stenosis was found in 14 cases, including 12 cases involving trachea and 2 cases involving trachea and subglottic area.There were 18 cases of grade Ⅲ, all of which involved the cervical trachea 5 cases failed in operation in other hospitals. According to stenosis grading, course of disease, primary disease control and the patient's general condition, the surgical plan was determined individually. The operations of end-to-end anastomosis, circumferential tracheal partial resection, T-tube placement and CO2 laser tracheal scar resection were performed respectively. The recovery of airway function and perioperative complications were observed one year after operation. Results: End-to-end anastomosis was performed in 16 cases, and partial circumferential tracheal resection in 2 cases, and tracheal granulation (scar) resection by CO2 laser in 2 cases and T-tube insertion in 12 cases. Eighteen cases which performed end-to-end anastomosis, partial resection of circumferential trachea in and 2 cases which performed laser tracheal scar resection were all recovered airway function at one stage. After 1 year, 19 cases were cured and 1 case was effective. Of 12 patients with T tube implantation, 11 cases were successfully extubated after 6-12 months, 7 cases were cured after 1 year, 2 cases were effective and 3 cases were ineffective. Among the 3 cases of failure, 2 cases were successfully extubated by sleeve resection and end-to-end anastomosis in the second stage, and the other case refused to accept other treatment methods and the T-tube was placed again, and the tube was blocked and the patient survived. During the follow-up period, the total cure rate was 87.5%, the effective rate was 9.4%, and the total extubation rate was 96.9%.The most common complication was subcutaneous emphysema, accounting for 78% (25/32), but no serious mediastinal emphysema or pneumothorax occurred. In the T-tube implantation group, granulation tissue grew in different degrees around the neck wound after operation, and improved or disappeared after 6-9 months. Anterior cervical tracheal fistula occurred in 4 cases of T-tube implantation group after extubation, which were cured by sealing the stoma. There were no complications such as severe bleeding or perioperative death. Conclusion: When there were various factors, the optimization of the surgical plan according to the degree of stenosis, the course of disease, the control of primary disease and the general condition was an important guarantee to improve the curative effect of laryngotracheal stenosis.

Shake It Up Baby Now: The Changing Focus on TWIST1 and Epithelial to Mesenchymal Transition in Cancer and Other Diseases.

TWIST1 is a transcription factor that is necessary for healthy neural crest migration, mesoderm development, and gastrulation. It functions as a key regulator of epithelial-to-mesenchymal transition (EMT), a process by which cells lose their polarity and gain the ability to migrate. EMT is often reactivated in cancers, where it is strongly associated with tumor cell invasion and metastasis. Early work on TWIST1 in adult tissues focused on its transcriptional targets and how EMT gave rise to metastatic cells. In recent years, the roles of TWIST1 and other EMT factors in cancer have expanded greatly as our understanding of tumor progression has advanced. TWIST1 and related factors are frequently tied to cancer cell stemness and changes in therapeutic responses and thus are now being viewed as attractive therapeutic targets. In this review, we highlight non-metastatic roles for TWIST1 and related EMT factors in cancer and other disorders, discuss recent findings in the areas of therapeutic resistance and stemness in cancer, and comment on the potential to target EMT for therapy. Further research into EMT will inform novel treatment combinations and strategies for advanced cancers and other diseases.

[Association between different treatment timings and adverse neonatal outcomes in pregnant women with syphilis during pregnancy].

Objective: To analyze the association between different treatment timings and adverse neonatal outcomes (premature birth, death, congenital syphilis) in syphilis-infected pregnant women. Methods: The National Management Information System for Prevention of HIV, Syphilis and HBV Mother-to-Child Transmission was used to collect information on the detection and treatment of syphilis-infected pregnant women and their newborns in Guangdong Province from October 2011 to December 2021. According to the gestational weeks of syphilis-infected pregnant women receiving penicillin treatment for the first time, they were divided into four groups: treatment in the first trimester, treatment in the second trimester, treatment in the third trimester, and no treatment during pregnancy. Multivariate logistic regression was used to analyze the association between different treatment timings and adverse neonatal outcomes in syphilis-infected pregnant women. Results: A total of 22 483 syphilis-infected pregnant women were included. The number of pregnant women who started treatment in the first trimester, second trimester, and third trimester and did not receive treatment during pregnancy were 4 549 (20.23%), 8 719 (38.78%), 2 235 (9.94%) and 6 980 (31.05%), respectively. Compared with pregnant women who started treatment in the first trimester, pregnant women who did not receive anti-syphilis treatment during pregnancy had increased risks of neonatal preterm birth (OR=1.42, 95%CI: 1.24-1.62), death (OR=4.27, 95%CI: 1.64-14.69) and congenital syphilis (OR=12.26, 95%CI: 6.35-27.45). At the same time, the risk of congenital syphilis in the newborns of pregnant women who started anti-syphilis treatment in the second trimester (OR=2.68, 95%CI: 1.34-6.16) and third trimester (OR=6.27, 95%CI: 2.99-14.80) also increased. Conclusion: Early initiation of anti-syphilis treatment during pregnancy in patients with syphilis can improve neonatal outcomes.

Meat taxes in Europe can be designed to avoid overburdening low-income consumers.

Consumption taxes on meat have recently been under consideration in several European countries as part of their effort to achieve more sustainable food systems. Yet a major concern is that these taxes might burden low-income households disproportionately. Here we compare different meat tax designs and revenue recycling schemes in terms of their distributional impacts in a large sample of European countries. We find that across all selected tax designs, uncompensated meat taxes are slightly regressive. However, the effect on inequality is mild and can be reversed through revenue recycling via uniform lump-sum transfers in most cases. Using meat tax revenues towards lowering value-added taxes on fruit and vegetable products dampens but does not fully offset the regressive effect. Variation in the distributional impact can be explained by cross-country heterogeneity in consumption patterns, design choices between unit-based and ad valorem taxation and differentiation according to greenhouse gas intensities.

[Analysis of the serum bile acid profile to facilitate diagnosis and differential diagnosis of NA(+)-taurocholate cotransporting polypeptide deficiency].

Objective: This study focuses on Na(+)-taurocholate cotransporting polypeptide (NTCP) deficiency to analyze and investigate the value of the serum bile acid profile for facilitating the diagnosis and differential diagnosis. Methods: Clinical data of 66 patients with cholestatic liver diseases (CLDs) diagnosed and treated in the Department of Pediatrics of the First Affiliated Hospital of Jinan University from early April 2015 to the end of December 2021 were collected, including 32 cases of NTCP deficiency (16 adults and 16 children), 16 cases of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), 8 cases of Alagille syndrome, and 10 cases of biliary atresia. At the same time, adult and pediatric healthy control groups (15 cases each) were established. The serum bile acid components of the study subjects were qualitatively and quantitatively analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry. The data were plotted and compared using statistical SPSS 19.0 and GraphPad Prism 5.0 software. The clinical and bile acid profiles of children with NTCP deficiency and corresponding healthy controls, as well as differences between NTCP deficiency and other CLDs, were compared using statistical methods such as t-tests, Wilcoxon rank sum tests, and Kruskal-Wallis H tests. Results: Compared with the healthy control, the levels of total conjugated bile acids, total primary bile acids, total secondary bile acids, glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were increased in NTCP deficiency patients (P < 0.05). Compared with adults with NTCP deficiency, the levels of total conjugated bile acids and total primary bile acids were significantly increased in children with NTCP deficiency (P < 0.05). The serum levels of taurochenodeoxycholic acid, glycolithocholate, taurohyocholate, and tauro-α-muricholic acid were significantly increased in children with NTCP deficiency, but the bile acid levels such as glycodeoxycholic acid, glycolithocholate, and lithocholic acid were decreased (P < 0.05). The serum levels of secondary bile acids such as lithocholic acid, deoxycholic acid, and hyodeoxycholic acid were significantly higher in children with NTCP deficiency than those in other CLD groups such as NICCD, Alagille syndrome, and biliary atresia (P < 0.05). Total primary bile acids/total secondary bile acids, total conjugated bile acids/total unconjugated bile acids, taurocholic acid, serum taurodeoxycholic acid, and glycodeoxycholic acid effectively distinguished children with NTCP deficiency from other non-NTCP deficiency CLDs. Conclusion: This study confirms that serum bile acid profile analysis has an important reference value for facilitating the diagnosis and differential diagnosis of NTCP deficiency. Furthermore, it deepens the scientific understanding of the changing characteristics of serum bile acid profiles in patients with CLDs such as NTCP deficiency, provides a metabolomic basis for in-depth understanding of its pathogenesis, and provides clues and ideas for subsequent in-depth research.

[Brief introduction on compilation and editions of Yang ke xuan cui].

Yang ke xuan cui («¼) is a surgical work compiled by Chen Wenzhi () of the Ming Dynasty. There are few of research on the completion and author of the book. Based on the evidences in the local chronicles, the prefaces and postscripts of the book, it has been verified that the book was originally completed no later than 1591, and Chen Wenzhi passed away no later than 1623. After investigating the 6 editions collected by 8 institutions, a collection of 11 books in total, by comparing the characteristics and circulation relationship of each edition, two systems of circulation were sorted out: block-printed edition of Xu Xi () and review edition of Xu Dachun ().

[Progress in the application of artificial intelligence in gastric cancer imaging].

Gastric cancer is a common malignant tumor of digestive tract, and its prognosis varies greatly with different stages of the tumor. In recent years, more and more evidence shows that artificial intelligence (AI) technology has excellent performance in imaging diagnostic applications, with remarkable diagnostic effects and broad prospects. AI not only improves the accuracy of diagnosis and staging of gastric cancer, but also has great application value in pathological assessment, adjuvant therapy and prognosis prediction. This article systematically reviews domestic and foreign literature to explore the application progress of AI in gastric cancer imaging.

[Prognostic value of a predictive model comprising preoperative inflammatory response and nutritional indexes in patients with gastric cancer].

Objective: To investigate the prognostic value of preoperative inflammatory and nutritional condition detection in the postoperative survival, and establish a prognostic model for predicting the survival of patients with gastric cancer. Methods: The clinicopathological data of 1123 patients with gastric cancer who had undergone radical gastrectomy in Tianjin Medical University Cancer Institute & Hospital from January 2005 to December 2014 were retrospectively analyzed. Patients with history of other malignancy, with history of gastrectomy, who had received preoperative treatment, who died during the initial hospital stay or first postoperative month, and missing clinical and pathological information were excluded. Cox univariate and multivariate analyses were used to identify independent clinicopathological factors associated with the survival of these gastric cancer patients. Cox univariate analysis was used to identify preoperative inflammatory and nutritional indexes related to the survival of patients with gastric cancer after radical gastrectomy. Moreover, the Cox proportional regression model for multivariate survival analysis (forward stepwise regression method based on maximum likelihood estimation) was used. The independent clinicopathological factors that affect survival were incorporated into the following three new prognostic models: (1) an inflammatory model: significant preoperative inflammatory indexes identified through clinical and univariate analysis; (2) a nutritional model: significant preoperative nutritional indexes identified through clinical and univariate analysis; and (3) combined inflammatory/nutritional model: significant preoperative inflammatory and nutritional indexes identified through clinical and univariate analysis. A model that comprised only pT and pN stages in tumor TNM staging was used as a control model. The integrated area under the receiver operating characteristic curve (iAUC) and C-index were used to evaluate the discrimination of the model. Model fitting was evaluated by Akaike information criterion analysis. Calibration curves were used to assess agreement between the predicted probabilities and actual probabilities at 3-year or 5-year overall survival (OS). Results: The study cohort comprised 1 123 patients with gastric cancer. The mean age was 58.9±11.6 years, and 783 were males. According to univariate analysis, age, surgical procedure, extent of lymph node dissection, tumor location, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and nerve invasion were associated with 5-year OS after radical gastrectomy for gastric cancer (all P<0.050). Multivariate analysis further identified age (HR: 1.18, 95%CI: 1.03-1.36, P=0.019), maximum tumor size (HR: 1.19, 95%CI: 1.03-1.38, P=0.022), number of examined lymph nodes (HR: 0.79, 95%CI: 0.68-0.92, P=0.003), pT stage (HR: 1.40, 95%CI: 1.26-1.55, P<0.001) and pN stage (HR: 1.28, 95%CI: 1.21-1.35, P<0.001) as independent prognostic factors for OS of gastric cancer patients. Additionally, according to univariate survival analysis, the preoperative inflammatory markers of neutrophil count, percentage of neutrophils, neutrophil/lymphocyte ratio, platelet/neutrophil ratio and preoperative nutritional indicators of serum albumin and body mass index were potential prognostic factors for gastric cancer (all P<0.05). On the basis of the above results, three models for prediction of prognosis were constructed. Variables included in the three models are as follows. (1) Inflammatory model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, and neutrophil-lymphocyte ratio; (2) nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and serum albumin; and (3) combined inflammatory/nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, neutrophil-lymphocyte ratio, and serum albumin. We found that the predictive accuracy of the combined inflammatory/nutritional model, which incorporates both inflammatory indicators and nutrition indicators (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.698),was superior to that of the inflammation model (iAUC: 0.662, 95% CI: 0.673-0.706;C-index: 0.675), nutritional model (iAUC: 0.666, 95% CI: 0.642-0.698, C-index: 0.672), and TNM staging control model (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.658). Furthermore, the combined inflammatory/nutritional model had better fitting performance (AIC: 10 762) than the inflammatory model (AIC: 10 834), nutritional model (AIC: 10 810), and TNM staging control model (AIC: 10 974). Conclusions: Preoperative percentage of neutrophils, NLR, and BMI have predictive value for the prognosis of gastric cancer patients. The inflammatory / nutritional model can be used to predict the survival and prognosis of gastric cancer patients on an individualized basis.

Transforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib.

Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy, largely due to metastasis and drug resistant recurrences. Fifteen percent of ovarian tumors carry mutations in BRCA1 or BRCA2, rendering them vulnerable to treatment with PARP inhibitors such as olaparib. Recent studies have shown that TGFß can induce "BRCAness" in BRCA wild-type cancer cells. Given that TGFß is a known driver of epithelial to mesenchymal transition (EMT), and the connection between EMT and metastatic spread in EOC and other cancers, we asked if TGFß and EMT alter the susceptibility of EOC to PARP inhibition. Epithelial EOC cells were transiently treated with soluble TGFß, and their clonogenic potential, expression, and function of EMT and DNA repair genes, and response to PARP inhibitors compared with untreated controls. A second epithelial cell line was compared to its mesenchymal derivative for EMT and DNA repair gene expression and drug responses. We found that TGFß and EMT resulted in the downregulation of genes responsible for homologous recombination (HR) and sensitized cells to olaparib. HR efficiency was reduced in a dose-dependent manner. Furthermore, mesenchymal cells displayed sensitivity to olaparib, cisplatin, and the DNA-PK inhibitor Nu-7441. Therefore, the treatment of disseminated, mesenchymal tumors may represent an opportunity to expand the clinical utility of PARP inhibitors and similar agents.

Association between sarcopenia and prediabetes among non-elderly US adults.

AIM: To explore the specific association between sarcopenia and prediabetes based on large population samples. METHODS: A total of 16,116 U.S. adults aged 20-59 with dual energy X-ray absorptiometry (DXA) was identified from the National Health and Nutrition Examination Surveys (NHANES). Sarcopenia was defined according to appendicular skeletal muscle mass (ASM) adjusted for body mass index (BMI). Multivariable binary logistic regression models were used to ascertain odds ratios (ORs) for developing prediabetes. Stratified analyses were also performed. RESULTS: Prevalence of prediabetes was higher in the sarcopenia group (n = 1055) compared with the non-sarcopenia group (n = 15,061) (45.50% vs 28.74%, P < 0.001). Sarcopenia was strongly associated with an increased risk of prediabetes after full adjustment (OR = 1.21, 95CI%: 1.05, 1.39, P = 0.009). In the stratified analysis, this association remained significant independent of obesity, triglycerides, and low-density lipoprotein cholesterol levels. When sarcopenia subjects combined with obesity especially central obesity, the risk of prediabetes was the highest (OR = 2.63, 95CI%: 2.22, 3.11, P < 0.001). Furthermore, a greater proportion of any of impaired glucose tolerance (IGT) individuals was observed in the sarcopenia group compared to the non-sarcopenia group among prediabetes population (41.72% vs 24.06%, P < 0.001). CONCLUSIONS: Sarcopenia was positively associated with prevalent prediabetes especially IGT in the non-elderly. Moreover, synergistic interactions between the sarcopenia and obesity could greatly increase the risk of prediabetes.

[Safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant chemotherapy combined with immunotherapy].

Objective: To investigate the safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy. Methods: Between November 2020 and April 2021, patients with locally advanced gastric cancer who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology were prospectively enrolled in this study. Inclusion criteria were: (1) patients who signed the informed consent form voluntarily before participating in the study; (2) age ranging from 18 to 75 years; (3) patients staged preoperatively as cT3-4N+M0 by the TNM staging system; (4) Eastern Collaborative Oncology Group score of 0-1; (5) estimated survival of more than 6 months, with the possibility of performing R0 resection for curative purposes; (6) sufficient organ and bone marrow function within 7 days before enrollment; and (7) complete gastric D2 radical surgery. Exclusion criteria were: (1) history of anti-PD-1 or PD-L1 antibody therapy and chemotherapy; (2) treatment with corticosteroids or other immunosuppre- ssants within 14 days before enrollment; (3) active period of autoimmune disease or interstitial pneumonia; (4) history of other malignant tumors; (5) surgery performed within 28 days before enrollment; and (6) allergy to the drug ingredients of the study. Follow-up was conducted by outpatient and telephone methods. During preoperative SOX chemotherapy combined with PD-1 inhibitor immunotherapy, follow-up was conducted every 3 weeks to understand the occurrence of adverse reactions of the patients; follow-up was conducted once after 1 month of surgical treatment to understand the adverse reactions and survival of patients. Observation indicators were: (1) condition of enrolled patients; (2) reassessment after preoperative therapy and operation received (3) postoperative conditions and pathological results. Evaluation criteria were: (1) tumor staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system; (2) tumor regression grading (TRG) of pathological results were evaluated with reference to AJCC standards; (3) treatment-related adverse reactions were evaluated according to version 5.0 of the Common Terminology Criteria for Adverse Events; (4) tumor response was evaluated by CT before and after treatment with RECIST V1.1 criteria; and (5) Clavien-Dindo complication grading system was used for postoperative complications assessment. Results: A total of 30 eligible patients were included. There were 25 males and 5 females with a median age of 60.5 (35-74) years. The primary tumor was located in the gastroesophageal junction in 12 cases, in the upper stomach in 8, in the middle stomach in 7, and in the lower stomach in 3. The preoperative clinical stage of 30 cases was III. Twenty-one patients experienced adverse reactions during neoadjuvant chemotherapy combined with immunotherapy, including four cases of CTCAE grade 3-4 adverse reactions resulting in bone marrow suppression and thoracic aortic thrombosis. All cases of adverse reactions were alleviated or disappeared after active symptomatic treatment. Among the 30 patients who underwent surgery, the time from chemotherapy combined with immunotherapy to surgery was 28 (23-49) days. All 30 patients underwent laparoscopic radical gastrectomy, of which 20 patients underwent laparoscopic-assisted radical gastric cancer resection; 10 patients underwent total gastrectomy for gastric cancer, combined with splenectomy in 1 case and cholecystectomy in 1 case. The surgery time was (239.9±67.0) min, intraoperative blood loss was 84 (10-400) ml, and the length of the incision was 7 (3-12) cm. The degree of adenocarcinoma was poorly differentiated in 18 cases, moderately differentiated in 12 cases, nerve invasion in 11 cases, and vascular invasion in 6 cases. The number lymph nodes that underwent dissection was 30 (17-58). The first of gas passage, the first postoperative defecation time, the postoperative liquid diet time, and the postoperative hospitalization time of 30 patients was 3 (2-6) d, 3 (2-13) d, 5 (3-12) d, and 10 (7-27) d, respectively. Postoperative complications occurred in 23 of 30 patients, including 7 cases of complications of Clavien-Dindo grade IIIa or above. Six patients improved after treatment and were discharged from hospital, while 1 patient died 27 days after surgery due to granulocyte deficiency, anemia, bilateral lung infection, and respiratory distress syndrome. The remaining 29 patients had no surgery-related morbidity or mortality within 30 days of discharge. Postoperative pathological examination showed TRG grades 0, 1, 2, and 3 in 8, 9, 4, and 9 cases, respectively, and the number of postoperative pathological TNM stages 0, I, II, and III was 8, 7, 8, and 7 cases, respectively. The pCR rate was 25.0% (8/32). Conclusion: Laparoscopic surgery after neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy for locally advanced gastric cancer is safe and feasible, with satisfactory short-term efficacy. Early detection and timely treatment of related complications are important.

[Clinical features and predictors of early neurological deterioration in acute isolated pontine infarction].

Objective: To investigate the clinical and imaging characteristics of early neurological deterioration (END) in acute isolated pontine infarction (AIPI) and analyze the predictive factors of END. Methods: Patients with AIPI who were confirmed by magnetic resonance imaging (MRI) in Zhengzhou University People's Hospital from January 2020 to December 2021were collected and divided into END group and non-END group (NEND group). General data and imaging characteristics of the patients were compared between the two groups, the neurological function of patients was evaluated by using the modified Rankin scale (mRS) at 1 and 3 months after stroke. Multivariate binary logistic regression model was used to analyze the risk factors of END after isolated pontine infarction, and the receiver operating characteristic curve(ROC) curve was drawn. Z-test was used to compare the area under the curve to determine the best predictor of END. Results: A total of 113 patients with AIPI were enrolled, including 72 males and 41 females, aged (62±11) years, with 40 cases in the END group and 73 cases in the NEND group. The incidence of END in AIPI was 35.4% (40/113). The National Institutes of Health Stroke Scale (NIHSS) score in the END group (5.15±1.88) was higher than that in the NEND group (4.10±1.63), and the infarcts size in the END group [(2.15±0.39) mm2] was larger than that in the NEND group [(1.61±0.46) mm2] (P=0.002 and P<0.001, respectively). Multivariate binary logistic regression analysis showed that NIHSS score on admission (OR=1.393, 95%CI: 1.017-1.909, P=0.039), infarct size (OR=11.539, 95%CI: 3.574-37.255, P<0.001) were associated with END. Comparing the area of ROC curve, infarct size [area under curve (AUC)=0.787, with a sensitivity of 0.750 and specificity of 0.545] and NIHSS score on admission (AUC=0.688, with a sensitivity of 0.700 and specificity of 0.589) showed no significant difference in the value of predicting END (P=0.056). Conclusion: Patients with AIPI had higher NIHSS score and larger infarct size on admission, and both of them exhibit good predictive performance for END.

Phenylacetylglutamine as a novel biomarker of type 2 diabetes with distal symmetric polyneuropathy by metabolomics.

PURPOSE: Type 2 diabetes mellitus (T2DM) with distal symmetric polyneuropathy (DSPN) is a disease involving the nervous system caused by metabolic disorder, while the metabolic spectrum and key metabolites remain poorly defined. METHODS: Plasma samples of 30 healthy controls, 30 T2DM patients, and 60 DSPN patients were subjected to nontargeted metabolomics. Potential biomarkers of DSPN were screened based on univariate and multivariate statistical analyses, ROC curve analysis, and logistic regression. Finally, another 22 patients with T2DM who developed DSPN after follow-up were selected for validation of the new biomarker based on target metabolomics. RESULTS: Compared with the control group and the T2DM group, 6 metabolites showed differences in the DSPN group (P < 0.05; FDR < 0.1; VIP > 1) and a rising step trend was observed. Among them, phenylacetylglutamine (PAG) and sorbitol displayed an excellent discriminatory ability and associated with disease severity. The verification results demonstrated that when T2DM progressed to DSPN, the phenylacetylglutamine content increased significantly (P = 0.004). CONCLUSION: The discovered and verified endogenous metabolite PAG may be a novel potential biomarker of DSPN and involved in the disease pathogenesis.

[A multicenter, double-blind, randomized controlled clinical trial comparing ergometrine with oxytocin and oxytocin alone for prevention of postpartum hemorrhage at cesarean section].

Objective: To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS). Methods: This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration. Results: (1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant (P<0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P<0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P>0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups (P>0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant (P<0.05), but the blood pressure of the two groups were in the normal range. Conclusion: The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.