As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*

Objective:To analyze the clinical data of children with hydrocephalus suffering from subdural effusion/hematoma after shunt(SEHS) with adjustable valves, and to provide reference for postoperative follow-up.Methods:A total of 102 children with hydrocephalus treated with adjustable valves in the Department of Neurosurgery, Wuhan Children′s Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from August 2017 to September 2021 were enrolled and studied retrospectively.There were 16 cases with SEHS, 11 of whom were male and 5 were female.The age ranged from 3 months to 13 years (median: 2.5 years). The age, clinical manifestations, the time of SEHS occurrence, treatment methods(pressure regulation only or combined with drilling and drainage), and prognosis of the patients were analyzed.The pressure adjustment treatment was to increase the by 10-20 mmH 2O (1 mmH 2O=0.009 8 kPa) each time and the patients were followed up 2-4 weeks after the adjustment.If SEHS didn′t improve according to the follow-up results, pressure regulation combined with drilling and drainage was recommended. Results:Of the 16 patients with SEHS, 3 cases were over 3 years old, and the other 13 cases were 3 years old or below.Eleven cases were treated by pressure regulation only, and 5 cases who were all aged ≤3 years received pressure regulation combined with drilling and drainage.Symptoms occurred in 2 patients, including vomiting in 1 case, and head and limb shaking in the other case.Fourteen cases were asymptomatic.The time from shunt operation to the occurrence of SEHS was ≤1 month in 5 cases, who were all cured by pressure regulation only.SEHS occurred in 5 cases >1-3 months after shunt surgery, and 2 cases of them were treated by pressure regulation combined with dri-lling and drainage.Three cases had SEHS>3-6 months after shunt surgery, and 1 case of them was treated by pressure regulation combined with drilling and drainage.SEHS occurred in 3 cases more than 6 months after shunt surgery, and 1 case of them was treated by pressure regulation combined with drilling and drainage.For the patients who received pressure regulation combined with drilling and drainage, the time from shunt operation to the occurrence of SEHS was 1 month and 21 days, 2 months and 7 days, 4.5 months, 7.5 months, and 25.0 months, respectively.The time from the occurrence of SEHS to the last reexamination with no SEHS detected was ≤1 month in 7 cases (all were cured by pressure regulation only); >1-3 months in 5 cases (3 cases were treated by pressure regulation combined with drilling and drainage); more than 3 months in 4 cases (2 cases were treated by pressure regulation combined with drilling and drainage). For the patients who received pressure regulation combined with drilling and drainage, the time from the occurrence of SEHS to the last reexamination with no SEHS detected was 1 month and 14 days, 2.0 months, 3.0 months, 7.0 months and 8.0 months, respectively.Except for 2 cases who experienced pressure regulating valve failure, all other cases were cured.Six cases were unilateral SEHS, and the SEHS volume was about 11 to 75 mL (median: 39.0 mL). Ten cases were bilateral SEHS, and the SEHS volume was about 23-380 mL (median: 158.2 mL). The 6 cases were all cured by pressure regulation, and 5 cases of them had SEHS at the shunt tube insertion side.Conclusions:SEHS in children with hydrocephalus is generally asymptomatic and rarely causes clinical symptoms.SEHS mostly occurs within 6 months after operation, especially within 3 months.SEHS found in 1 month after surgery can be cured by increasing the shunt valve pressure only.Therefore, SEHS can be cured by pressure regulation only by shortening follow-up and identifying SEHS early after shunt operation.This will also reduce the probability that patients require the drilling and drainage operation.

Objective: To observe the clinical efficacy and safety of transhepatic arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in the treatment of colorectal cancer with liver metastasis. Methods: The data of 92 patients with colorectal cancer with liver metastasis admitted to Nanyang First People′s Hospital of Henan Province from January 2014 to January 2016 were retrospectively analyzed. A total of 46 patients treated with TACE were selected as the TACE group, and another 46 patients treated with TACE and RFA were selected as the combined group. The clinical efficacies of the two groups were compared, and the changes of Karnofsky functional status (KPS) scores before and after treatment in the two groups were analyzed. The incidences of complications in the two groups were calculated. Patients in the two groups were followed up, and the progress-free survival (PFS) and overall survival (OS) were calculated. Results: The disease control rate of the combined group was 82.61% (38/46), and that of the TACE group was 63.04% (29/46). The disease control rate of the combined group was higher than that of the TACE group (χ²=4.449, P=0.035). Before treatment, the KPS scores of the combined group and the TACE group were 71.84±4.37, 72.22±4.26, with no statistically significant difference (t=0.423, P=0.673). After treatment, the KPS scores of the two groups were higher than those before treatment, and the KPS score of the combined group was higher than that of the TACE group (79.81±6.15 vs. 75.86±6.02; t=3.108, P=0.003). The incidence of complications was 54.35% (25/46) in the combined group and 41.30% (19/46) in the TACE group. The difference between the two groups was not statistically significant (χ²=1.568, P=0.210). The median PFS and OS in the TACE group were 12.6 and 20.7 months, and those in the combined group were 18.9 and 28.2 months. The PFS and OS of the combined group were longer than those of the TACE group (χ²=72.025, P<0.001; χ²=26.580, P<0.001). Conclusion TACE combined with RFA is effective in the treatment of liver metastasis of colorectal cancer, which can effectively improve the KPS score of patients, prolong the PFS and OS, and do not increase the risk of complications.

Objective: To explore the clinical value of new rapid pathological diagnosis technology in biliary biopsy by endoscopic retrograde cholangiopancreatography (ERCP). Methods: 7 patients with biliary biopsy by ERCP were selected. In the biliary biopsyoperation, a new type of rapid pathological diagnostic technique is used to perform cytological initial diagnosis of the biopsy tissue. According to the results of rapid pathological diagnosis of biliary biopsy operation, we analyzed the clinical value of new rapid pathological diagnosis technology in the biliary biopsy operation. Results: The new rapid pathological diagnosis technology requires little space and no pollution. The diagnosis takes about 2 to 3 minutes and does not affect the normal biopsy operation. 7 patients with biliary biopsy by ERCP under the assistance of this technique, 5 patients (71.4%) confirmed the requirement of biopsy quality and quantity for the first biopsy with the assistance of this technology and 2 patients (28.6%) met the requirements for biopsy quality and quantity after biopsy again. Conclusions Because of the blindness of biliary biopsy by ERCP, the quality and quantity of biopsy tissue are often not guaranteed. The new rapid pathological diagnosis technology can provide real-time pathological diagnosis during biliary biopsy by ERCP and improve the quality and quantity of biliary biopsy tissue, and the cost of this technology is low, which is suitable for popularization and implementation in hospitals at all levels.

After reviewing literature, this paper will briefly introduce the research progress on toxicity-reducing and efficacy-enhancing through compatibility of Radix Aconiti Lateralis Praeparata in recent years. It includes five parts:modern basic study of Radix Aconiti Lateralis Praeparata; research on toxicity-reducing and efficacy-enhancing of complete or separate prescription of Sini Tang; research of the herb-pair in compatible prescription; studying the efficacy of herbal prescription of Radix Aconiti Lateralis Praeparata by utilizing complex biological networks; further research of Radix Aconiti Lateralis Praeparata and its prospect.

OBJECTIVETo determine the incidence, risk factors and clinical outcomes of postoperative delirium in colorectal cancer patients over 60 years.

METHODSConsecutive 382 patients older than 60 years undergoing colorectal cancer surgery at Shenzhen Second People's Hospital from June 2013 to June 2016 were recruited prospectively in this study. These patients were evaluated daily after surgery for 7 days by confusion assessment method. Clinical outcomes were compared between patients with and without postoperative delirium, including postoperative complications, length of hospital stay, and mortality within 30 days. Logistic regression analysis was used to identify independent predictors of postoperative delirium.

RESULTSThere were 230 male and 152 female patients with median age of 67(range 60 to 92) years. Among them, 213 had colon cancer and 169 had rectal cancer. Postoperative delirium developed in 46(12.0%) patients, and most deliriums (78.3%) were diagnosed within 3 days after surgery. Patients with postoperative delirium had more complications [30.4%(14/46) vs. 17.3%(58/336), P=0.032], higher mortality [6.5%(3/46) vs. 1.8%(6/336), P=0.047], and longer postoperative hospital stay (median 14 days vs. 9 days, P=0.008). Univariate analysis revealed that advanced age, male, higher Charlson comorbidity index, higher American Society of Anesthesiologists Classification, lower preoperative blood albumin concentration, history of psychiatric disease, history of cerebrovascular disease, alcohol abuse, emergent operation, and perioperative blood transfusion were significantly related to the development of postoperative delirium. Logistic regression analysis identified that advanced age (OR=1.06, 95%CI: 1.01 to 1.13), history of psychiatric disease (OR=10.89, 95%CI: 2.73 to 41.59) and perioperative blood transfusion (OR=2.37, 95%CI: 1.11 to 7.32) were independent risk factors of postoperative delirium.

CONCLUSIONSPostoperative delirium is relatively common in elderly patients over 60 years undergoing colorectal cancer surgery. The high morbidity of postoperative complication and mortality associated with postoperative delirium warrant implementation of preoperative risk assessment and postoperative screening protocol for postoperative delirium. Comprehensively preventive strategies should be carried out for high-risk patients, e.g. advanced age, history of psychiatric disease, and perioperative blood transfusion.

Irritable bowel syndrome( IBS)is a common functional gastrointestinal disease,relevant investigations on pathogenesis of IBS mainly focus on genetic susceptibility, social psychological stress, visceral hypersensitivity, dysregulation of brain-gut axis,dysbiosis of intestinal flora,and dysimmunity of intestinal mucosa. This article reviewed the correlation between dysbiosis of intestinal microbiota and dysregulation of brain-gut axis in IBS.

Functional gastrointestinal disease is a group of clinical syndrome of non-organic disease. Its various clinical symptoms have a certain specificity and overlap phenomenon, and the mechanism is not clear. TCM believes thatphychological factorsare an important cause. Emotion failurecan effect spleen and stomach functionthrough liver and heart directly or indirectly.At present, the phychological factors and the relationship between functional gastrointestinal disease are getting attentiongradually. It is recognized that the mechanism of phychological factorsmay be related to brain axis dysfunction, mast cell activation, intestinal flora and so on. This article expounded the above-mentioned mechanism and reviewed the detailed TCM intervention measures to functional gastrointestinal disease in recent years.

Objective To investigate the intervention of Pixu Fang 1 (Spleen-deficiency Formula 1) to the protein and mRNA expressions of myosin light chain (MLC) in gastric tissue in rats with functional dyspepsia (FD)-spleen deficiency pattern(SDP).Methods SD rats (n =60,aged 7 d) were randomly divided into normal group (n =10) and FD-SDP model group (n =50).The normal group was orally given 2％ sugar solution and FD-SDP model group was given 0.1％ iodoacetamide sugar solution in a dose of O.2 mL each rat a day for 6 d.The FD-SDP model group was fed with normal forage until rats aged 6 weeks and additionally given modified multiple platform method (MMPM) continuously for 14 d.After modeling,FD-SDP model group was divided randomly into model group (distilled water,10 mL/kg · d),domperidone group (3.125 mg/kg · d),low-dose Pixu Fang 1 group (low-dose group,1.275 g/ kg · d),mid-dose Pixu Fang 1 group (mid-dose group,2.550 g/kg · d) and high-dose Pixu Fang 1 group (high-dose group,5.100 g/kg · d,each n =10),and all groups were given orally corresponding medicinal for 14 d.The protein and mRNA expressions of MLC in gastric tissue were detected by using immunohistochemistry technique,Western blotting and reverse transcription-polymerase chain reaction (RT-PCR).Results Compared with normal group,MLC protein expression decreased in model group detected by immunohistochemistry technique and Western blotting,and MLC mRNA expression decreased in model group detected by RT-PCR (P ＜0.01).Compared with model group,MLC protein expression increased in low-dose group,mid-dose group and high-dose group detected by immunohistochemistry technique (P ＜ 0.05,P ＜ 0.01).MLC protein expression increased in mid-dose group and high-dose group detected by Western blotting (P ＜ 0.O1).MLC mRNA expression increased in high-dose group detected RT-PCR (P ＜ 0.01).Conclusion There are decreases of protein and mRNA expressions of MLC in FD-SDP rats,and Pixu Fang 1 can up-regulate these expressions.

Objective To explore the effect of tonifying kidney with traditional Chinese medicine together with estradiol valerate and clomiphene citrate on serum leptin levels in patients with polycystic ovarian syndrome. Method Two hundred and eight patients with PCOS were randomly divided into observation group (n=104) and control group (n=104). Patients in control group and observation group took estradiol valerate and clomiphene citrate, while patients in observation group took Shiying Minlin soup for three months. Crinosity, body temperature, acne&Skin diseases, and menoxenia were recorded; Leptin (LP) and five hormone including follicle stimulating hormone (FSH),luteinizing hormone (LH), prolactin (PRL), estradiol (E 2) and testosterone (T) are determined using euzymelinked immunosorbent assay. Results Crinosity, body temperature, acne&Skin diseases, and menoxenia were improved;the level of FSH, LH, PRL, E 2, T in both observation and control group decreased and the content in observation group are high than that in control group, while LH,T and E 2 are lower. Conclusion Treatment with tonifying kidney with traditional Chinese medicine on polycystic ovarian syndrome can decrease the level of FSH, LH, PRL, E 2, T and LP. Compared with western medicine, tonifying kidney with traditional Chinese medicine showed advantage in the terms of treatment on polycystic ovarian syndrome.