OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Objective:To investigate the clinical characteristics of omphalocele, and to assess the risk factors associated with adverse outcomes.Methods:A retrospective cohort study was conducted. Clinical data of 224 patients diagnosed with omphalocele, who were hospitalized at Children′s Hospital, Zhejiang University School of Medicine from January 2013 to December 2022, were collected. Based on their discharge outcomes, the patients were classified into 2 groups: favorable outcomes and unfavorable outcomes. Chi-square test or continuity correction χ2 test or Fisher exact probability method, and Mann-Whitney U test were used for intergroup comparisons. Logistic regression analysis was performed to identify risk factors associated with adverse outcomes in omphalocele. Results:Among the 224 patients with omphalocele, 126 were male. A total of 208 patients (92.9%) had favorable outcomes, while 16 patients (7.1%) had unfavorable outcomes. In the unfavorable outcomes group, 14 patients had giant omphaloceles, while 100 patients had giant omphaloceles in the favorable outcomes group. The rates of herniation of more than two intra-abdominal organs in the hernial sac, congenital heart defects, patent ductus arteriosus, pulmonary hypertension, sepsis and infection of the hernial sac, were all higher in the unfavorable outcomes group compared to the favorable outcomes group (all P<0.05). Patients with unfavorable outcomes had longer mechanical ventilation time, duration of oxygen use, duration of parenteral nutrition, hospital stays, and higher rates of parenteral nutrition-associated cholestasis compared to those with favorable outcomes (all P<0.01). Multivariate Logistic regression analysis indicated that pulmonary hypertension ( OR=9.39, 95% CI 1.20-73.32), sepsis ( OR=8.59, 95% CI 1.32-55.86), and congenital heart defects ( OR=6.55, 95% CI 1.11-38.73) were all independent risk factors for adverse outcomes in omphalocele (all P<0.05). Conclusions:Infants with omphalocele are prone to complications such as cardiovascular malformations, infections, and pulmonary hypertension. Adverse outcomes in omphalocele are associated with pulmonary hypertension, sepsis, and congenital heart defects.

Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%, mainly including lung adenocarcinoma (LUAD). Tumor microenvironment (TME) has become a new research focus in the treatment of lung cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. The various cellular components exert a different role in apoptosis, metastasis, or proliferation of lung cancer cells through different pathways, thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods. This review summarizes the research progress on different cellular components with cell-cell interactions in the TME of LUAD, along with their corresponding drug candidates, suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.
Humans ; Tumor Microenvironment/drug effects* ; Adenocarcinoma of Lung/drug therapy* ; Lung Neoplasms/pathology* ; Adenocarcinoma/metabolism* ; Animals ; Apoptosis/physiology*

Chimeric antigen receptor-modified T(CAR-T)cell therapy,as a new type of cellular immunotherapy,has shown good clinical efficacy in the treatment of malignant hematological tumors,especially B-cell acute lympho-blastic leukemia.However,there are problems such as antigen loss and immune evasion in single-target selection,so multi-target therapy strategies are gradually gaining attention.Multi-target CAR-T can effectively avoid antigen escape caused by a single target by targeting multiple tumor-associated antigens at the same time,reduce the risk of recurrence,and is expected to improve the therapeutic effect.This paper primarily discusses the structural types of multi-target CAR-T cell therapy and its clinical trial applications in the treatment of B-cell acute lymphoblastic leu-kemia(B-ALL),aiming to provide future references for the treatment of B-ALL.

OBJECTIVE: To explore the clinical characteristics and genetic variant in a premature infant with Netherton syndrome (NS). METHODS: A neonate with NS caused by variants of SPINK5 gene diagnosed at the Children's Hospital Affiliated to Zhejiang University School of Medicine in March 2020 was selected as the study subject. Clinical data and family history were collected. Peripheral blood samples (2 mL each) were obtained from the child and her parents for whole-exome sequencing (WES). Candidate variants were subjected to pathogenicity classification and deleteriousness evaluation. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-IRB-0251-P-01). RESULTS: The infant was born prematurely at 35⁺³ weeks due to "premature rupture of membranes for 4 hours" and exhibited generalized skin peeling, with meconium-stained amniotic fluid resembling bean curd residue. The condition improved with supportive treatments such as anti-infection and moisturizing therapy, though periodic hair loss had persisted. No similar case was reported by family history. WES has revealed a heterozygous c.1130delG (p.G377Efs*127) variant in exon 14 of the SPINK5 gene, which was inherited from her mother, and deletion of exons 1 ~ 33 of the SPINK5 gene, which was inherited from her father. CONCLUSION This case of NS presented with intrauterine onset in a preterm infant, which has not been previously reported. The identification of c.1130delG (p.G377Efs*127) variant has expanded the mutation spectrum of the SPINK5 gene.
Humans ; Serine Peptidase Inhibitor Kazal-Type 5/genetics* ; Netherton Syndrome/genetics* ; Female ; Infant, Newborn ; Infant, Premature ; Mutation ; Exome Sequencing ; Male

Objective:To evaluate the relationship between pelvimetric parameters and surgical difficulty in robot-assisted total mesorectal excision (TME) performed by experienced colorectal surgeons, and to build a nomogram model.Methods:This was a retrospective observational study. The inclusion criteria were as follows: (1) tumor within 10 cm of the anal verge; (2) cancer confirmed by pathological examination of the postoperative specimen; (3) preoperative complete magnetic resonance imaging (MRI) data available; (4) depth of tumor invasion T1-3; (5) circumferential resection margin assessed as negative by MRI; and (6) R0 resection achieved. The exclusion criteria comprised (1) history of pelvic fractures; (2) history of pelvic surgery; and (3) emergency required because of tumor-related intestinal obstruction and/or perforation. Application of above criteria yielded 82 patients who had undergone robot-assisted total mesorectal excision of mid and low rectal cancer in the Department of Colorectal Surgery of the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2022 (modeling group). Additionally, data of 35 patients with mid and low rectal cancer who had undergone robotic-assisted TME at the same center in 2023 January–August were collected for validation of the model (validation group). The following 13 pelvic parameters were studied: pelvic inlet diameter, pelvic outlet diameter, pubic tubercle height, sacral height, sacral depth, interspinous distance, inter-tuberosity distance, lateral mesorectal span, anterior-posterior mesorectal span, anterior mesorectal thickness, posterior mesorectal thickness, rectal area, and mesorectal area. Operating time was used as an indicator of the degree of surgical difficulty, this being defined as the time from the start of skin incision to the end of abdominal closure. Variables related to the duration of surgery were subjected to univariate and multivariate logistic regression analyses to identify factors associated with the difficulty of TME, after which a nomogram for predicting the difficulty of the procedure was established. We constructed receiver operating characteristic and calibration curves to validate the predictive power of nomogram. Furthermore, data from the validation group were used for external validation of the model.Results:The model group comprised 82 patients, including 54 men and 28 women of median age 61.0 years. The median body mass index (BMI) was 23.7 kg/m 2, median distance between the tumor and anal verge 6.1 cm, and median tumor diameter 4.5 cm. Fourteen of these patients had received preoperative adjuvant therapy and 12 had a history of abdominal surgery. There were 35 patients (24 men and 11 women) of median age 64.0 years in the validation group. Their median BMI was 23.7 kg/m 2 and median distance between the tumor and anal verge 6.3 cm. Multivariable analyses of the model group showed that BMI (OR=1.227, 95%CI: 1.240–1.469, P=0.026), distance between the tumor and anal verge (OR=0.733, 95%CI: 0.562–0.955, P=0.022), and interspinous distance (OR=0.468, 95%CI: 0.270–0.812, P=0.007) were independent predictors of surgical difficulty. We then built and validated a predictive nomogram based on the above three variables (AUC=0.804, 95%CI: 0.707–0.900). Calibration curves showed that the S:P in this model was 0.987 and the C-index 0.804. Area under the receiver operating characteristic curve of the predictive model in the validation dataset was 0.767 (95%CI: 0.606–0.928). Conclusion:MRI-based measurements of pelvic parameters are associated with difficulty of performing robot-assisted TME for mid and low rectal cancer. Our nomogram model constructed based on measurements of pelvic parameters has a good predictive ability.

Objective:To evaluate the relationship between pelvimetric parameters and surgical difficulty in robot-assisted total mesorectal excision (TME) performed by experienced colorectal surgeons, and to build a nomogram model.Methods:This was a retrospective observational study. The inclusion criteria were as follows: (1) tumor within 10 cm of the anal verge; (2) cancer confirmed by pathological examination of the postoperative specimen; (3) preoperative complete magnetic resonance imaging (MRI) data available; (4) depth of tumor invasion T1-3; (5) circumferential resection margin assessed as negative by MRI; and (6) R0 resection achieved. The exclusion criteria comprised (1) history of pelvic fractures; (2) history of pelvic surgery; and (3) emergency required because of tumor-related intestinal obstruction and/or perforation. Application of above criteria yielded 82 patients who had undergone robot-assisted total mesorectal excision of mid and low rectal cancer in the Department of Colorectal Surgery of the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2022 (modeling group). Additionally, data of 35 patients with mid and low rectal cancer who had undergone robotic-assisted TME at the same center in 2023 January–August were collected for validation of the model (validation group). The following 13 pelvic parameters were studied: pelvic inlet diameter, pelvic outlet diameter, pubic tubercle height, sacral height, sacral depth, interspinous distance, inter-tuberosity distance, lateral mesorectal span, anterior-posterior mesorectal span, anterior mesorectal thickness, posterior mesorectal thickness, rectal area, and mesorectal area. Operating time was used as an indicator of the degree of surgical difficulty, this being defined as the time from the start of skin incision to the end of abdominal closure. Variables related to the duration of surgery were subjected to univariate and multivariate logistic regression analyses to identify factors associated with the difficulty of TME, after which a nomogram for predicting the difficulty of the procedure was established. We constructed receiver operating characteristic and calibration curves to validate the predictive power of nomogram. Furthermore, data from the validation group were used for external validation of the model.Results:The model group comprised 82 patients, including 54 men and 28 women of median age 61.0 years. The median body mass index (BMI) was 23.7 kg/m 2, median distance between the tumor and anal verge 6.1 cm, and median tumor diameter 4.5 cm. Fourteen of these patients had received preoperative adjuvant therapy and 12 had a history of abdominal surgery. There were 35 patients (24 men and 11 women) of median age 64.0 years in the validation group. Their median BMI was 23.7 kg/m 2 and median distance between the tumor and anal verge 6.3 cm. Multivariable analyses of the model group showed that BMI (OR=1.227, 95%CI: 1.240–1.469, P=0.026), distance between the tumor and anal verge (OR=0.733, 95%CI: 0.562–0.955, P=0.022), and interspinous distance (OR=0.468, 95%CI: 0.270–0.812, P=0.007) were independent predictors of surgical difficulty. We then built and validated a predictive nomogram based on the above three variables (AUC=0.804, 95%CI: 0.707–0.900). Calibration curves showed that the S:P in this model was 0.987 and the C-index 0.804. Area under the receiver operating characteristic curve of the predictive model in the validation dataset was 0.767 (95%CI: 0.606–0.928). Conclusion:MRI-based measurements of pelvic parameters are associated with difficulty of performing robot-assisted TME for mid and low rectal cancer. Our nomogram model constructed based on measurements of pelvic parameters has a good predictive ability.

In order to further strengthen the training and management of clinical teachers, broaden the career development channels of clinical teachers, and truly stimulate their teaching enthusiasm and initiative, this study further classifies clinical teachers according to the principle of the Snell model, focuses on the training of educational clinicians, and explores the training mechanism of teaching talents in line with the actual development needs of hospitals affiliated to universities from the aspects of selection, training, incentive, and assessment. The results of practice show that related practices have a good effect, and the mean number of teaching achievements was 1.98 for the 56 educational physicians, which was 3.9 times that for non-educational physicians. The per capita teaching achievements of educational physicians tended to increase every year compared with those of non-educational physicians. The training path for educational physicians provides useful experience for the construction of clinical teaching team and the high-quality development of education and teaching, and at the same time, it is necessary to further strengthen the dynamic adjustment of talent echelon, the improvement of operating mechanism, and the introduction of new technology.

Objective:To determine the median effective dose (ED 50) of ciprofol inhibiting responses to insertion of laryngeal mask airway in the patients when combined with alfentanil. Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients of either sex, aged 40-64 yr, with body mass index of 20-30 kg/m 2, undergoing elective general anesthesia, were enrolled. Midazolam 0.025 mg/kg was intravenously injected for anesthesia induction, the baseline mean arterial pressure and heart rate were recorded 5 min later, and the average value of three times was considered as the baseline value. Ciprofol and alfentanil 10 μg/kg were intravenously injected in sequence, rocuronium 0.6 mg/kg was intravenously injected when BIS value < 60, 2 min later a laryngeal mask airway was placed, and mechanical ventilation was performed. Positive response was defined as increase in the maximum mean arterial blood pressure or heart rate more than or equal to 20% of the baseline value within 3 min after placement of the laryngeal mask airway or as the occurrence of body movement, bucking, frowning, mouth and face twitching, tearing, laryngospasm or the BIS value failing to drop below 60. The study was performed by the Dixon′s up-and-down method. The initial dose of ciprofol was 0.4 mg/kg, and the ratio between the two successive doses was 1.1. If a positive response occurred, the dose was increased in the next patient, otherwise the dose was reduced. The ED 50 and 95% confidence interval of ciprofol inhibiting responses to insertion of laryngeal mask airway were calculated by the probit method. Results:The ED 50(95% confidence interval) of ciprofol inhibiting responses to insertion of laryngeal mask airway was 0.291(0.231-0.318) mg/kg when combined with alfentanil 10 μg/kg. Conclusions:The ED 50 of ciprofol inhibiting responses to insertion of laryngeal mask airway is 0.291 mg/kg in the patients when combined with alfentanil 10 μg/kg.