Tumor microenvironment(TME)is the living environment of tumor cells.The immune cells contained in TME are reprogrammed into tumor-promoting states due to various factors.Inhibiting this reprogramming effect of TME is an innovative strategy for treating tumors.As an essential factor in spindle assembly,TPX2 is considered to be a gene that promotes cancer cell proliferation and plays a role in cell response to replication stress.Highly expressed TPX2 in tumor cells promotes tumor growth through a variety of pathways,and these pathways can promote the tumor-promoting activity of immune cells in TME.Therefore,TPX2 may be a regulatory gene of TME.This paper discusses the possible mechanism of TPX2 involved in the regulation of TME by discussing the pathway medi-ated by TPX2 and the regulation of immune cells infiltrated in TME,and provides ideas for subsequent research directions.

Tumor microenvironment(TME)is the living environment of tumor cells.The immune cells contained in TME are reprogrammed into tumor-promoting states due to various factors.Inhibiting this reprogramming effect of TME is an innovative strategy for treating tumors.As an essential factor in spindle assembly,TPX2 is considered to be a gene that promotes cancer cell proliferation and plays a role in cell response to replication stress.Highly expressed TPX2 in tumor cells promotes tumor growth through a variety of pathways,and these pathways can promote the tumor-promoting activity of immune cells in TME.Therefore,TPX2 may be a regulatory gene of TME.This paper discusses the possible mechanism of TPX2 involved in the regulation of TME by discussing the pathway medi-ated by TPX2 and the regulation of immune cells infiltrated in TME,and provides ideas for subsequent research directions.

Objective:To explore the long-term efficacy of laparoscopic fundoplication for proton pump inhibitor dependent gastroesophageal reflux disease (GERD).Method:Clinical data of proton pump inhibitor dependent GERD patients who underwent fundoplication at the Rocket Force Characteristic Medical Center from Jan to Jun 2012 were analyzed, including GERD symptom score, subjective symptom relief rate, PPI discontinuation rate and surgical satisfaction, as well as recurrence and complications.Result:A total of 160 GERD patients were included in this study, with 64% of patients having respiratory symptoms. Nissen and Toupet fundoplication were performed in 43 and 117 cases, respectively, with a follow-up time of (127±3) months. The postoperative GERD symptom scores of the patients were significantly lower than before treatment (all P<0.001); The subjective relief of overall symptoms in the digestive tract and airway problem was 90% (80%, 100%) and 100%, respectively. The PPI discontinuation rate was 86%, and the overall satisfaction rate of the treatment was 92%, and the satisfaction rate of patients with respiratory symptoms was 89%. 7% of patients experienced varying degrees of symptomatic recurrence, 4% of patients re-underwent endoscopic treatment and/or laparoscopic fundoplication due to symptom recurrence. The incidence of long-term postoperative dysphagia, bloating, belching, increased exhaust, abdominal pain, diarrhea, and constipation were 11.3%, 16.9%, 0, 1.3%, 0, 2.5%, and 5.6%, respectively. Conclusions:Laparoscopic fundoplication has good long-term efficacy in the treatment of GERD. A small number of patients may experience postoperative recurrence, as well as complications such as dysphagia and gas-bloat syndrome. Most recurrent patients can achieve good therapeutic effect by redoing endoscopic treatment or redoing surgery.

Objective:To evaluate the efficacy and safety of micropulse transscleral cyclophotocoagulation (MP-TSCPC) for refractory glaucoma.Methods:A prospective multicenter observational case series study was conducted.A total of 63 refractory glaucoma patients (67 eyes) who underwent MP-TSCPC treatment were enrolled at Zhongshan Ophthalmic Center, Sun Yat-sen University, Chengdu First People's Hospital (Chengdu Integrated TCM& Western Medicine Hospital), and Changsha Aier Eye Hospital from August 2022 to April 2023.Among these cases, there were 40 eyes (59.7%) with unreduced intraocular pressure (IOP) after glaucoma surgery, 4 eyes (6.0%) with secondary glaucoma after vitrectomy, 2 eyes (3.0%) with secondary glaucoma after keratoplasty, 8 eyes (11.9%) with neovascular glaucoma, 3 eyes (4.5%) with secondary glaucoma due to iridocorneal endothelial syndrome, 6 eyes (9.0%) with primary open-angle glaucoma and 4 eyes (6.0%) with primary angle-closure glaucoma.Best corrected visual acuity (BCVA) was measured using the ETDRS chart and the IOP was measured using the Goldmann applanation tonometry before and 6 months after the surgery.The usage of anti-glaucoma medications before and after surgery and postoperative complications were recorded.Surgical success rate was calculated and surgical success was defined as an IOP reduction of more than 20% from baseline or a reduction in the number of ocular hypotensive medications with no change in IOP.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2022KYPJ225).Written informed consent was obtained from each subject.Results:There was a statistically significant overall difference in IOP at different time points before and after surgery ( F=60.10, P<0.001), and the IOP at different time points after surgery was significantly lower than that before surgery, with statistically significant differences (all at P<0.001).IOP reduction at 6 months after surgery was (43.7±20.7)%.The number of anti-glaucoma medications used postoperatively was 2(0, 3) types, which was significantly less than the 3(2, 3) types used preoperatively ( Z=-2.70, P=0.007).The 6-month postoperative BCVA (LogMAR) was 1.40(0.52, 2.70), which showed no significant change compared to the preoperative 1.40(0.70, 2.70) ( Z=-0.10, P=0.952).The surgical success rate was 83.6%(56/67) at 6 months postoperatively.Postoperative complications included mydriasis (11/67), conjunctival hemorrhage (11/67), mild anterior chamber inflammation (1/67), mild ciliary body detachment (3/67), local choroidal detachment (1/67), and cystoid macular edema (1/67), all of which were reversible after treatment. Conclusions:MP-TSCPC appears to be a safe and effective treatment option for refractory glaucoma.

This paper discussed how to set the limit of impurities in the quality standard when the impurities in small-molecular innovative drugs were metabolites.Firstly,through the analysis and interpretation of each relevant guideline,in combination with the review cases of FDA and EMA,found out the conditions for qualification of im-purity,and then establ ish the acceptable limit of impurities based on the test results of multiple batches,the incre-ments of production process and storage process.

Objective:To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease.Method:This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result:Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged ( M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) ( κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) ( κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn′t affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions:Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

Objective:To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease.Method:This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result:Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged ( M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) ( κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) ( κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn′t affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions:Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

Objective:To summarize and analyze the results of gene detection and clinical characteristics of children with unknown etiology in pediatric intensive care unit (PICU).Methods:The clinical data from children with unknown clinical diagnosis and completed the whole exon sequencing who were admitted to PICU at Hunan Children's Hospital from September 20,2014 to December 30,2018 were collected .According to the results of gene detection,patients were divided into positive gene test group and regative gene test group,and the clinical characteristics between two groups were compared.Results:A total of 58 cases were included,and 119 samples were sent for the whole exone sequencing (including samples from both children and their families).Pathogenic mutations were identified in 34 cases (58.6%),with 39 pathogenic genes detected.Three pathogenic genes were detected in one patient (1.7%),two pathogenic genes were detected in each of the three patients (5.2%),and one pathogenic gene was detected in each of the 30 patients (51.7%).Among the 39 pathogenic genes,18 genes(46.2%) were autosomal dominant,15 genes(38.5%) were autosomal recessive,four genes(10.3%) were X-linked recessive,and two genes(5.1%) were copy number variants .The proportion of congenital heart disease in positive gene test group was higher than that in negative gene test group（32.4% vs.8.3%，χ 2=4.668， P=0.031）,while there was no statistical difference in other clinical features（ P>0.05）.There was no significant difference in clinical characteristics between the positive gene test group and the negative gene test group among the death children ( P>0.05）.Among 58 cases,39 cases (67.2%) resulted in death,and the positive rate of genetic disease diagnosis of the dead children was 66.7%(26/39).The mortality rate of children with positive genetic test was 76.5%(26/34),22 cases (84.7%) died directly from genetic diseases,and four cases died indirectly. Conclusion:Genetic diseases are one of the important causes of death among children in PICU.The clinical characteristics of children with genetic diseases in PICU are complex and diverse,lacking specificity.The whole exon sequencing presents a high diagnosis rate in severe and fatal PICU patients.It is recommended that children with unknown etiology in PICU should undergo genetic testing,especially those with congenital heart disease,in order to help make a clear diagnosis and guide treatment.

Objective:To summarize and analyze the results of gene detection and clinical characteristics of children with unknown etiology in pediatric intensive care unit (PICU).Methods:The clinical data from children with unknown clinical diagnosis and completed the whole exon sequencing who were admitted to PICU at Hunan Children's Hospital from September 20,2014 to December 30,2018 were collected .According to the results of gene detection,patients were divided into positive gene test group and regative gene test group,and the clinical characteristics between two groups were compared.Results:A total of 58 cases were included,and 119 samples were sent for the whole exone sequencing (including samples from both children and their families).Pathogenic mutations were identified in 34 cases (58.6%),with 39 pathogenic genes detected.Three pathogenic genes were detected in one patient (1.7%),two pathogenic genes were detected in each of the three patients (5.2%),and one pathogenic gene was detected in each of the 30 patients (51.7%).Among the 39 pathogenic genes,18 genes(46.2%) were autosomal dominant,15 genes(38.5%) were autosomal recessive,four genes(10.3%) were X-linked recessive,and two genes(5.1%) were copy number variants .The proportion of congenital heart disease in positive gene test group was higher than that in negative gene test group（32.4% vs.8.3%，χ 2=4.668， P=0.031）,while there was no statistical difference in other clinical features（ P>0.05）.There was no significant difference in clinical characteristics between the positive gene test group and the negative gene test group among the death children ( P>0.05）.Among 58 cases,39 cases (67.2%) resulted in death,and the positive rate of genetic disease diagnosis of the dead children was 66.7%(26/39).The mortality rate of children with positive genetic test was 76.5%(26/34),22 cases (84.7%) died directly from genetic diseases,and four cases died indirectly. Conclusion:Genetic diseases are one of the important causes of death among children in PICU.The clinical characteristics of children with genetic diseases in PICU are complex and diverse,lacking specificity.The whole exon sequencing presents a high diagnosis rate in severe and fatal PICU patients.It is recommended that children with unknown etiology in PICU should undergo genetic testing,especially those with congenital heart disease,in order to help make a clear diagnosis and guide treatment.

Objective:To compare the application effect among Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scale, Medical Outcomes Study 36-item Short Form (SF-36) scale and "Assessment for Therapeutic Efficacy on Kashin-Beck Disease" (WS/T 79-2011) standard in the evaluation of therapeutic effect of patients with Kashin-Beck disease, which could provide basis for the treatment evaluation of patients with Kashin-Beck disease.Methods:A total of 213 patients with Kashin-Beck disease in Gansu Province were investigated. WOMAC scale, SF-36 scale and standard of WS/T 79-2011 were used to analyze the quality of life of patients before and after treatment. The reliability, construct validity, content validity, discriminant validity of WOMAC and SF-36 scales were compared. Correlation between WOMAC, SF-36 scales and standard of WS/T 79-2011 were evaluated.Results:Both WOMAC and SF-36 scales had good construct validity and content validity (construct validity showed WOMAC and SF-36 scales contained 1 and 2 common factors, respectively; content validity showed WOMAC and SF-36 scales contained 3 and 8 common factors, respectively). The reliability and discriminant validity of WOMAC scale were better than those of SF-36 seale (reliability showed WOMAC reliability coefficient ≥0.934, the reliability coefficient of SF-36 scale was ranged from 0.386 to 0.999. Discriminant validity showed there were differences in 3 dimensions of the WOMAC scale before and after treatment, while there were differences in 6 out of 8 dimensions of the SF-36 scale). The correlation coefficients between WOMAC scale and standard of WS/T 79-2011 ranged from 0.175 to 0.437, the correlation coefficients between SF-36 scale and standard of WS/T 79-2011 ranged from - 0.434 to - 0.099 ( P < 0.05). Conclusion:The reliability, discriminant validity and correlation with the standard of WS/T 79-2011 of WOMAC scale are better than those of SF-36 scale in efficacy evaluation of patients with Kashin-Beck disease.