Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

OBJECTIVE To compare the antibacterial drugs between the 2021 edition of WHO Model List of Essential Medicines for Children （WHO EMLc） and the 2018 edition of National Essential Medicines List of China （NEML）， and provide reference for the drug selection of Chinese essential medicine list for children.　METHODS By means of descriptive analysis， the similarities and differences in classification methods， special markers， the varieties， dosage forms and specifications were compared between WHO EMLc and NEML.　RESULTS WHO EMLc had strict limits and classifications on the antibacterial drugs， marked the age and weight of children who were restricted to use， and focused on the drug resistances and safety in children. In terms of varieties， there were 51 kinds of antibacterial drugs in NEML and 62 in WHO EMLc； 36 kinds of antibacterial drugs were both included in NEML and WHO EMLc； some antibacterial drugs， such as cloxacillin， procaine penicillin and ceftazidime avibactam， were listed in WHO EMLc but not in NEML. In terms of dosage forms， the dosage forms of antibacterial drugs included in WHO EMLc were more abundant and flexible， such as oral liquids， powder for oral liquids and scored tablets which were not included in NEML， and could improve the compliance of children’s medication and the accuracy of dosage. In terms of specifications， the total numbers of the specifications of antibacterial drugs both included in the two lists were close， but the specifications of some drugs included in NEML were more abundant， and the minimum specifications included in NEML were smaller. Although some of the unique antibacterial drugs included in WHO EMLc were listed in China， they could not be used in children due to the lack of drug data on children in China， such as clofazimine， bedaquinoline and delamanid.　CONCLUSIONS The antibacterial drugs included in NEML can not fully meet the medication needs of children in China. WHO EMLc has certain advantage and rationality as a special list for children. The relevant departments in China can learn from the excellent experience of WHO EMLc， improve the information of pediatric medication of NEML and launch Chinese Essential Medicine List for Children as soon as possible.

COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread across the globe, posing an enormous threat to public health and safety. Traditional Chinese medicine (TCM), in combination with Western medicine (WM), has made important and lasting contributions in the battle against COVID-19. In this review, updated clinical effects and potential mechanisms of TCM, presented in newly recognized three distinct phases of the disease, are summarized and discussed. By integrating the available clinical and preclinical evidence, the efficacies and underlying mechanisms of TCM on COVID-19, including the highly recommended three Chinese patent medicines and three Chinese medicine formulas, are described in a panorama. We hope that this comprehensive review not only provides a reference for health care professionals and the public to recognize the significant contributions of TCM for COVID-19, but also serves as an evidence-based in-depth summary and analysis to facilitate understanding the true scientific value of TCM.

【Objective】 To analyze the clinical characteristics of patients with primary carcinoma of the gallbladder (PGC) who underwent radical intent resection in our center in the last decade and the therapeutic effects of the operation. 【Methods】 A single-institution database of The First Affiliated Hospital of Xi'an Jiaotong University from January 2008 to December 2017 was queried for patients with PGC who had received surgical treatment. The data were studied retrospectively to assess the trend of total admission, radical resection rate, prognosis and clinicopathological characteristics of PGC in the last decade. 【Results】 A total of 2 159 patients with PGC were treated in our institution from 2008 to 2017. Of them, 1072 were surgically treated and 503 underwent radical intent resection. In the past 5 years (2013-2017), the radical resection rate was 26.5% (319 cases of the operation), which was significantly higher than that in 2008-2012 (19.2%) (P<0.001). The overall survival time of the patients who underwent radical resection was 32 months, and the 1-, 3-, and 5-year survival rate was 68.9%, 48.4% and 41.6%, respectively. Compared with the data of 2008-2012, the proportion of the patients with preoperative jaundice decreased in the past 5 years (7.8% vs. 14.7%, P<0.05), that of the patients who underwent D2 lymphadenectomy (74.0% vs. 26.1%, P<0.001) increased significantly (P<0.001), the total number of lymph nodes obtained from the dissection (8.07±5.18 vs. 5.89±3.14, P<0.001) increased significantly (95.6% vs. 89.7%, P<0.05), and the proportion of R0 resection (95.6%) increased significantly (P<0.05). 【Conclusion】 The diagnosis and treatment of radical intent resection of PGC in our hospital have changed significantly in the last decade, mainly reflected in the extension of lymphadenectomy, increase in R0 resection rate and decrease in patients with preoperative jaundice.

Objective To investigate the clinical effects and prognostic factors of radical surgery for primary gallbladder cancer (GBC).Methods The retrospective case-control study was conducted.The clinicopathological data of 305 patients with primary GBC who underwent radical Ro resection in the First Affiliated Hospital of Xi'an Jiaotong University from 2013 to 2017 were collected,including 108 males and 197 females,aged from 30 to 88 years,with a median age of 62 years.According to the different tumor staging,patients underwent corresponding operation and adjuvant treatment based on the postoperative indication of chemotherapy.Observation indicators:(1) results of imaging and laboratory examinations;(2) treatment situations:① surgical situations,② postoperative adjuvant treatment;(3) results of postoperative pathological examination;(4) followup;(5) prognostic factors analysis.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 5,2018,and death was used as the end point.Measurement data with normal distribution were represented as Mean±SD.Measurement data with skewed distribution were described as M (range).Count data were represented as percentage.The survival curve and survival rate were respectively drawn and calculated using the Kaplan-Meier method.The univariate analysis and multivariate analysis were respectively done using the Log-rank test and COX regression model.Results (1) Results of imaging and laboratory examinations:results of imaging examination showed that diagnostic rates of ultrasound,CT and MRI examination were respectively 84.06％ (174/207),85.71％ (168/196) and 63.11％ (65/103).Results of laboratory examination showed that the positive rates of CA19-9,CA125 and carcinoembryonic antigen (CEA) were respectively 55.34％ (145/262),48.06％ (124/258) and 46.15％ (126/273).(2) Treatment situations:① surgical situations:305 patients underwent radical R0 resection for primary GBC,including 145 undergoing liver wedge resection + D2 lymph node dissection,61 undergoing liver wedge resection + D1 lymph node dissection,55 undergoing liver Ⅳ B and Ⅴ segmentectomy + D2 lymph node dissection,11 undergoing liver Ⅳ B and Ⅴ segrnentectomy + D1 lymph node dissection,9 undergoing right hepatectomy + D2 lymph node dissection,5 undergoing liver wedge resection + D2 lymph node dissection + partial colectomy,4 undergoing pancreaticoduodenectomy,3 undergoing simple cholecystectomy in Tis stage,3 undergoing right hepatectomy + D1 lymph node dissection,2 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial colectomy,1 undergoing liver Ⅳ B and Ⅴ segmentectomy + resection and reconstruction of portal vein + D2 lymph node dissection,1 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial resection of the stomach or duodenum,1 undergoing pancreaticoduodenectomy + resection and reconstruction of portal vein,1 undergoing right hepatectomy + pancreaticoduodenectomy,1 undergoing right hepatic lobectomy + partial gastrectomy + D2 lymph node dissection,1 undergoing right hepatic lobectomy + D1 lymph node dissection and 1 undergoing right hepatic trilobectomy + D2 lymph node dissection.Of 94 patients with unsuspected GBC,78 who were diagnosed in the other hospitals received salvage surgery in the authors' center.Twenty-one patients had postoperative surgery-related complications,including 11 with bile leakage,8 with pulmonary infection and 2 with abdominal bleeding.Two patients died in the perioperative period.② Postoperative adjuvant treatment:26 patients underwent postoperative adjuvant chemotherapy.Chemotherapy regimen:gemcitabine + oxaliplatin were used in 12 patients,gemcitabine + tegafur in 7 patients,gemcitabine + cisplatin in 6 patients,oxaliplatin + tegafur in 1 patient.(3) Results of postoperative pathological examination.The postoperative pathological type of 305 patients:257,23,6,5,4,3,3,2,1 and 1 patients were respectively confirmed as pure adenocarcinoma,adenocarcinoma combined with squamous cell carcinoma,adenocarcinoma combined with neuroendocrine carcinoma,mucinous adenocarcinoma,neuroendocrine carcinoma,adenocarcinoma combined with mucinous carcinoma,squamous cell carcinoma,sarcomatoid carcinoma,adenocarcinoma combined with sarcomatoid carcinoma,adenocarcinoma combined with signet-ring cell carcinoma.Degree of tumor differentiation:highdifferentiated,moderate-differentiated and low-differentiated tumors were detected in 37,130 and 121 patients,respectively,17 with unknown differentiated degree.Of 305 patients,16 and 32 patients had respectively vascular invasion and nerve invasion.The number of lymph node dissected of 305 patients was 8±5,with positive lymph node of 0 (range,0-9),including 121 with lymphatic metastasis (26 with jumping lymphatic metastasis).TNM staging of 305 patients:stage 0,Ⅰ,Ⅱ,ⅢA,ⅢB,ⅣA and ⅣB were detected in 7,18,13,137,57,11 and 62 patients,respectively.(4) Follow-up:245 of 305 patients were followed up for 18.0 months (range,6.0-70.0 months).The survival time,1-and 3-year survival rates were respectively 29.5 months (range,0.5-69.9 months),71.6％ and 45.8％.One hundred and twenty-two patients died during the follow-up.(5) Prognostic factors analysis:the results of univariate analysis showed that preoperative level of bilirubin,pathological type,degree of tumor differentiation,liver invasion,vascular invasion,nerve invasion,T staging,N staging and postoperative chemotherapy were factors affecting prognosis of patients with primary GBC (x2 =10.26,3.96,45.89,34.64,12.75,27.05,35.09,39.44,4.40,P＜0.05).The results of multivariate analysis showed that low-differentiated tumor,liver invasion and N2 staging were independent risk factors affecting prognosis of patients with primary GBC [odds ratio (OR)=1.90,1.71,1.46,95％ confidence interval (CI):1.34-2.70,1.15-2.52,1.17-1.82,P＜0.05],and postoperative chemotherapy was a protective factor affecting prognosis of patients with primary GBC (OR=0.35,95％ CI:0.15-0.82,P＜0.05).Conclusions For patients with primary GBC undergoing radical resection,D2 lymph node dissection should be performed routinely.The low-differentiated tumor,liver invasion and N2 staging are independent risk factors affecting prognosis of patients,and postoperative chemotherapy is a protective factor.

Objective     To compare the efficacy of the single tube (ST) and double tube (DT) for closed thoracic drainage after lobectomy. Methods     The PubMed, Medline, EMbase, Web of Science, CNKI, Wanfang Database, VIP database and CBMdisc from inception to March 30, 2018 were searched by computer to identify randomized controlled trial (RCT) about ST and DT drainage after lobectomy. Based on inclusion and exclusion criteria the literature was screened. Meta-analysis was performed using RevMan 5.3 software. Results     Twelve RCTs were enrolled in this meta-analysis, including 1 442 patients. Compared with the patients using DT after lobectomy, the patients using ST had significantly less postoperative pain (MD=–0.64, 95%CI –0.71 to –0.56, P<0.000 01) and shorter duration of drainage (MD=–0.62, 95%CI –0.78 to –0.46, P<0.000 01) and hospital stay (MD=–0.55, 95%CI –0.80 to –0.29, P<0.000 1). Besides, there was no significant difference in postoperative complications (RR=1.11, 95%CI 0.83 to 1.49, P=0.49), air leaks (RD=0.03, 95%CI –0.02 to 0.08, P=0.19) and the redrainage rate (RR=0.89, 95%CI 0.51 to 1.54, P=0.67). Conclusion    ST drainage after lobectomy is effective, which reduces postoperative pain and duration of hospital stay and drainage, and moreover, does not increase the postoperative complications and redrainage rate.

Objective: To examine the value and clinical application of convolutional neural network in pathological diagnosis of metastatic lymph nodes of gastric cancer. Methods: Totally 124 patients with advanced gastric cancer who underwent radical gastrectomy plus D2 lymphadenectomy at Affiliated Hospital of Qingdao University from July 2016 to December 2018 were selected in the study. According to the chronological order, the first 80 cases were served as learning group. The remaining 44 cases were served as verification group. There were 45 males and 35 females in the study group, with average age of 57.6 years. There were 29 males and 15 females in the validation group, with average age of 9.2 years. The pre-training convolutional neural network architecture Resnet50 was trained and fine-tuned by 21 352 patches with cancer areas and 14 997 patches without cancer areas in the training group. A total of 78 whole-slide image served as a test dataset including positive (n=38) and negative (n=40) lymph nodes. The convolutional neural network computer-aided detection (CNN-CAD) system was used to analyze the ability of convolutional neural network system to screen metastatic lymph nodes at the level of slice by setting threshold, and evaluate the system′s classification accuracy by calculating its sensitivity, specificity, positive predictive value, negative predictive value and area under the receiver operating characteristic curve (AUC). Results: The classification accuracy of CNN-CAD system at slice level was 100%.The AUC for the CNN-CAD system was 0.89. The sensitivity was 0.778, specificity was 0.995, overall accuracy was 0.989. Positive and negative predictive values were 0.822 and 0.994, respectively. The CNN-CAD system achieved the same classification results as pathologists. Conclusions The CNN-CAD system has been constructed to distinguished benign and malignant lymph node slides with high accuracy and specificity. It could achieve the similar classification results as pathologists.

Objective To investigate the efficacy and safety of low-dose rituximab therapy and sequential maintenance for patients with refractory idiopathic thrombocytopenic purpura. Methods Thirty-three patients with refractory idiopathic thrombocytopenic purpura received intravenous rituximab at the dose of 100 mg once a week for 4 consecutive weeks. Complete blood cell count and serum concentrations of immunoglobulin (IgG,IgM and IgA) were monitored regularly. The numbers of CD3+ and CD19+ CD20+ lymphocyte cells were assayed by flow cytometry before and after therapy. Twenty-five patients with responses(complete response and response) were divided into maintained group (12 patients) and control group (13 patients) by random digits table method. The patients in maintained group were treated with rituximab 100 mg every 6 months. The efficacy of maintenance therapy was evaluated through long-term follow-up. Results The complete response(CR) rate, response (R) rate and no response(NR) rate were 48.48%(16/33), 27.27%(9/33) and 24.24% (8/33), respectively. As a result, total effective rate was 75.76% (25/33). There were no significant changes of peripheral blood white blood cell count,hemoglobin,serum immunoglobulin and CD3+lymphocyte counts before and after treatment (P>0.05). However, CD19+ CD20+ cells were almost depleted in patients treated with rituximab: (3.71±2.64)×106/L vs. (279.33±92.78)×106/L, P<0.01. Five patients suffered from allergic response, and 1 patient developed pneumonia and respiratory failure. The relapse rates of maintained group and control group were 1/12 and 4/13, respectively. Conclusions Treatment with low-dose rituximab may be an effective and safe approach in patients with idiopathic thrombocytopenic purpura. Relapse rates can be decreased through maintenance therapy with refractory low-dose rituximab. However, the optimal therapeutic schedule need further investigation.

Objective To learn whether plasmodium genetic attenuated sporozoites (GAS) can induce immunity against lung cancer ,in order to provide new ideas for the study of lung cancer vaccine .Methods Ther study was divided into two groups respec‐tively ,experimental group received intravenous injection of genetically attenuated sporozoites to immunize C57BL/6J mice and con‐trol group injection of phosphate buffer solution (PBS);after 14 days ,we subcutaneously inoculated lewis lung cancer (LLC) cells , calipers was used to measure tumor size .Immunohistochemical staining was detected tumor proliferation ,apoptosis ,and angiogene‐sis .Results There was statistically significant in tumor size .Immunohistochemical staining revealed that attenuated sporozoites in‐fection inhibited LLC eslls proliferation ,angiogenesis ,apoptosis .Conclusion The malaria attenuated sporozoites may provide a no‐vel strategy or therapeutic vaccine vector for anti‐lung cancer immune‐based therapy .

OBJECTIVETo evaluate the feasibility of endoscopic gastrostomy combined with magnetic compression techniques in dogs.

METHODSThe magnetic compression device consisted of a couple of cylindrical magnets with a hole in the center. A 14-French gastric tube was inserted through the hole and fixed on the parent magnets. Four male mongrel dogs were selected randomly for the operation. The daughter magnet was placed into the dog's gastric body by a Zebra Guidewire under endoscopy, then a skin incision was performed on the left upper abdomen, through which the subcutaneous tissues and muscle were isolated up to the peritoneum. The parent magnet was placed on the surface of the peritoneum, which attracted the daughter magnet inside the gastric cavity automatically to compress the gastric wall and peritoneum. A needle was inserted through the gastric tube and punctured the tissue in the hole of the magnets repeatedly to form a fistula. After removing the needle, the gastrostomy was complete. The fistula was observed and its specimen was taken two weeks later under laparotomy.

RESULTSAll the four operations were successfully performed, and the operation time was 11-15 minutes. The stoma was matured immediately, through which early enteral nutrition support was administered. The gastric wall and peritoneum were observed with well healing and no adhesion in the abdominal cavity under laparotomy two weeks after the operation.

CONCLUSIONThe gastrostomy performed by magnetic compression technique combined with endoscopy is convenient, minimally invasive and safe, which may be used in future clinical practice.

Abdomen ; Animals ; Catheterization ; Dogs ; Enteral Nutrition ; Gastroscopy ; Gastrostomy ; Laparotomy ; Magnetics ; Male ; Santonin ; analogs & derivatives ; Stomach ; Surgical Stomas ; Wound Healing