Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To investigate the expression of placenta expressed transcript 1(Plet1)in ovarian tissue of the letrozole-induced model rats of polycystic ovary syndrome(PCOS)and its effect on the proliferation of rat ovarian granulosa cells,and to clarify the possible mechanism by which Plet1 may contribute to the pathogenesis of PCOS.Methods:The ovarian tissue samples from the rats collected in previous studies were used and divided into control and PCOS groups.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the expression levels of Plet1 mRNA and protein in ovarian tissue of the rat in two groups.Additionally,twenty-four rats underwent vaginal smear cytology were divided into four groups by estrous cycle phase:proestrus,estrus,metestrus and diestrus.RT-qPCR was used to detect the expression level of Plet1 mRNA in ovarian tissue of the rats in various groups,and immunohistochemistry(IHC)method was used to detect the location of Plet1 expression in the rat ovarian tissue in various groups.The rat ovarian granulosa cells were transfected and divided into control group,si-Plet1-rat-266 group,si-Plet1-rat-383 group,and si-Plet1-rat-554 group.Cell counting kit-8(CCK-8)method was used to assess the cell proliferation activities of rat ovarian granulosa cells in various groups,and RT-qPCR method was used to detect the expression levels of cyclin-d epend ent kinase 6(CDK6)and P53 mRNA in rat ovarian granulosa cells in various groups.Results:The RT-qPCR results revealed that Plet1 mRNA was expressed in the ovaries of normal rats,while no statistically significant difference was observed across estrous cycle phases(P＞0.05).The immunohistochemistry results showed that the expression of Plet1 protein was mainly localized in ovarian granulosa cells and luteal cells in the rat ovarian tissue.Compared with control group,the expression levels of Plet1 mRNA and protein in ovarian tissue of the rats in PCOS group were significantly decreased(P＜0.05).The RT-qPCR results showed that compared with control group,the expression level of Plet1 mRNA in ovarian granulosa cells in si-Plet1-rat-383 group was decreased(P＜0.01),exhibiting the most pronounced reduction.Compared with control group,the proliferation activity of rat ovarian granulosa cells in si-Plet1-rat-383 group was decreased(P＜0.05).Compared with control group,the expression levels of CDK6 and P53 mRNA in rat ovarian granulosa cells in si-Plet1-rat-383 group were significantly decreased(P＜0.05 or P＜0.01).Conclusion:Plet1 protein is predominantly expressed and localized in granulosa cells and luteal cells in normal rat ovarian tissue.Its expression is downregulated in the ovarian tissue of PCOS model rats,and interference with Plet1 gene expression may inhibit the proliferation of rat ovarian granulosa cells.

Tumor microenvironment(TME)includes inflammatory,metabolic,and immune microenvironment,which interact in a complex network,influencing tumorigenesis,progression,and metastasis.Clinical studies on traditional Chinese medicine(TCM)have found that dampness pathogen plays a significant role in gastrointestinal precancerous lesions,tumorigenesis,and metastasis.It disrupts the gastrointestinal tumor's inflammatory,metabolic,and immune microenvironments,promoting tumor development through various mechanisms.Based on the theory of dampness pathogen,it is proposed to eliminate dampness combined with detoxification to regulate tumor inflammatory microenvironment;invigorate qi,warm yang,and remove dampness to regulate metabolic microenvironment;and strengthen the spleen,support vital energy,and dispel dampness to improve immunosuppressive microenvironment.Treating gastrointestinal tumors from the perspective of dampness pathogen theory can offer new insights and focus areas for clinical diagnosis and treatment,as well as directions for research into the molecular mechanisms of compound Chinese herbal formulas.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Tumor microenvironment(TME)includes inflammatory,metabolic,and immune microenvironment,which interact in a complex network,influencing tumorigenesis,progression,and metastasis.Clinical studies on traditional Chinese medicine(TCM)have found that dampness pathogen plays a significant role in gastrointestinal precancerous lesions,tumorigenesis,and metastasis.It disrupts the gastrointestinal tumor's inflammatory,metabolic,and immune microenvironments,promoting tumor development through various mechanisms.Based on the theory of dampness pathogen,it is proposed to eliminate dampness combined with detoxification to regulate tumor inflammatory microenvironment;invigorate qi,warm yang,and remove dampness to regulate metabolic microenvironment;and strengthen the spleen,support vital energy,and dispel dampness to improve immunosuppressive microenvironment.Treating gastrointestinal tumors from the perspective of dampness pathogen theory can offer new insights and focus areas for clinical diagnosis and treatment,as well as directions for research into the molecular mechanisms of compound Chinese herbal formulas.

Cancer is a prevalent and challenging disease that is difficult to treat.Western medicine recognizes the disruption of the immune and inflammatory microenvironment as a crucial factor in the development and progression of cancer.According to traditional Chinese medicine,cancer falls into the categories of"accumulation"and"abnormal masses".Based on the attributes of cold and heat in the overall and local conditions as well as the characteristic of the struggle between the vital qi and pathogenic factors at different stages of this disease,this article proposes the concept of"body coldness and tumor heat"to describe the pathogenesis of cancer formation and progression.This pathogenesis aligns with the disruption of the immune and inflammatory microenvironment in modern medical oncology.The article suggests a treatment approach that focuses on balancing cold and heat,nourishing and protecting yang qi,warming the kidneys,and strengthening the spleen to address the"coldness of the entire body".This approach also involves promoting qi circulation,eliminating dampness,phlegm,and stasis,and detoxifying and dispersing nodules to address the"heat in the tumor locally".By addressing deficiencies,eliminating pathogenic factors,and promoting circulation to alleviate stagnation,the aim is to restore the balance of yin and yang and improve the complex state of"coldness of the entire body"and"heat in the tumor locally".These interventions can ameliorate the disorder in the microenvironment and enhance clinical efficacy.

Objective:To investigate the feasibility of oblique overlap anastomosis plus single flap valvuloplasty (OSF) for reconstruction after laparoscopic proximal gastrectomy.Methods:The C-shaped seromuscular flap (2.5 × 3.5 cm), which was 2 cm from the top of the remnant stomach, was extracorporeally created on the anterior wall of the remnant stomach. The stomach was opened approximately 1.0 cm above the lower edge of the mucosal flap. Four supporting stitches were sutured around the hole and the right wall of the esophageal stump was incised with a support suture to prevent the linear stapler from entering the submucosa. Liner stapler was inclined to the left side of the esophagus at an angle of about 30 degrees to the longitudinal axis of the esophagus for oblique anastomosis between the dorsal side of the esophagus and the anterior stomach and then esophagogastrostomy was performed with the length of anastomosis was 4 cm. Entry hole was suture with 3 stitches and then the linear stapler was used for closing the entry hole. Finally, the seromuscular flap was closed using barbed sutures.Results:Clinical data of 11 patients with Siewert type II esophagogastric junction adenocarcinoma who underwent radical gastrectomy and reconstruction by OSF between January 2022 and May 2023 were retrospectively collected. There were 7 males and 4 females. The average age was (69.9±7.8) years, the BMI was (21.7±7.2) kg/m 2 and the tumor size was (2.1±0.6) cm. OSF reconstruction was successfully completed in all 11 patients. The median operative time was 275 (270-428) minutes, the time for OSF reconstruction was 112 (80-140) minutes, and the blood loss was 50 (20-400) ml. The pathological stage was 0-I in 7 cases and II-III in 4 cases. The patients were fed on the 4th day (4-7 days) and discharged from hospital on the 7th day (6-9 days) after surgery. No patient had gastroesophageal reflux symptoms of grade B and above, and no patient took anti-reflux medicine. Conclusions:OSF is a safe and feasible treatment for Siewert type II esophagogastric junction adenocarcinoma.

Objective:To summarize the clinical characteristics and first aid measures of children with drowning，and to provide scientific basis for the treatment and prevention of drowning in children.Methods:The clinical data of drowning children admitted to the Children's Medical Center of the First Affiliated Hospital of Hunan Normal University（Hunan Provincial People's Hospital）from January 2011 to December 2021 were retrospectively summarized. Baseline characteristics，prehospital emergency care and prognosis of the included children were analyzed.According to the time span, drowning children were divided into two stages, the first stage (2011-2016) and the second stage (2017-2021). According to cerebral performance category assessment scale,drowning children with cardiac arrest were divided into two groups: a group with good neurological prognosis and a group with poor neurological prognosis. The baseline characteristics,pre-hospital emergency care, and prognosis of drowning children during different periods and with different prognosis were analyzed.Results:A total of 53 children were enrolled during the study period，with 24 cases in the first phase（2011-2016）and 29 cases in the second phase（2017-2021）.Boys accounted for 73.6%（39/53）of the cases, the age ranged from 1 month and 24 days to 14 years old，with 1-4 years old being the most common，accounting for 58.5%（31/53）, and the season in which drowning occurred was more common in the summer（39.6%, 21/53）.Six cases (11.3%) had significant neurological sequelae, and the mortality rate was 3.8%（2/53）.There was a decrease in the proportion of drowning with water control in the second stage compared to the first stage（37.5% vs. 13.79%, P=0.046）.Thirty-two（60.4%）children experienced on-site cardiopulmonary resuscitation(CPR) after drowning，with 24 cases in the group with good neurological prognosis and 8 cases in the group with poor neurological prognosis.Children in the poor neurological prognosis group required CPR for a long duration [10.00（1.50, 25.00）min]，had lower body temperature，Glasgow Coma Score，pH and higher blood glucose levels on admission（all P < 0.05）. Conclusion:Drowning is most common in preschool children，common in boys，and drowning prevention measures for young children deserve focused attention. Children found to be in cardiac arrest at the time of drowning have a long duration of drowning and CPR，which predicts a poor neurological prognosis，and timely and effective on-site CPR is the key to reducing the drowning rate.

Objective:To investigate the feasibility of oblique overlap anastomosis plus single flap valvuloplasty (OSF) for reconstruction after laparoscopic proximal gastrectomy.Methods:The C-shaped seromuscular flap (2.5 × 3.5 cm), which was 2 cm from the top of the remnant stomach, was extracorporeally created on the anterior wall of the remnant stomach. The stomach was opened approximately 1.0 cm above the lower edge of the mucosal flap. Four supporting stitches were sutured around the hole and the right wall of the esophageal stump was incised with a support suture to prevent the linear stapler from entering the submucosa. Liner stapler was inclined to the left side of the esophagus at an angle of about 30 degrees to the longitudinal axis of the esophagus for oblique anastomosis between the dorsal side of the esophagus and the anterior stomach and then esophagogastrostomy was performed with the length of anastomosis was 4 cm. Entry hole was suture with 3 stitches and then the linear stapler was used for closing the entry hole. Finally, the seromuscular flap was closed using barbed sutures.Results:Clinical data of 11 patients with Siewert type II esophagogastric junction adenocarcinoma who underwent radical gastrectomy and reconstruction by OSF between January 2022 and May 2023 were retrospectively collected. There were 7 males and 4 females. The average age was (69.9±7.8) years, the BMI was (21.7±7.2) kg/m 2 and the tumor size was (2.1±0.6) cm. OSF reconstruction was successfully completed in all 11 patients. The median operative time was 275 (270-428) minutes, the time for OSF reconstruction was 112 (80-140) minutes, and the blood loss was 50 (20-400) ml. The pathological stage was 0-I in 7 cases and II-III in 4 cases. The patients were fed on the 4th day (4-7 days) and discharged from hospital on the 7th day (6-9 days) after surgery. No patient had gastroesophageal reflux symptoms of grade B and above, and no patient took anti-reflux medicine. Conclusions:OSF is a safe and feasible treatment for Siewert type II esophagogastric junction adenocarcinoma.

Objective:To investigate the predictive value of heparin binding protein(HBP) combined with pediatric sequential organ failure assessment(pSOFA) in children with sepsis.Methods:Children with sepsis admitted to PICU of Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University) from January 2021 to June 2022 were selected as study group,while those who underwent elective surgery for inguinal hernia and assessment of precocious puberty and short stature during the same period were selected as control group.All children with sepsis were divided into sepsis group and septic shock group according to their severity as well as survival group and death group according to prognosis.The study group was monitored for HBP on the 1st,3rd,and 7th day of admission,while the control group was monitored for HBP on the 1st day of admission.Patients in the sepsis group received pSOFA scores immediately after admission.The laboratory results and HBP concentrations were compared between groups，and a joint model was established in combination with pSOFA to observe its predictive performance in sepsis prognosis.Results:A total of 50 children with sepsis were included in study group，including 45 children with sepsis and five children with septic shock.There were 27 males and 23 females，aged 1 month～13 years（median age two years）.There were 7 deaths in this study，including two patients with sepsis and five patients with septic shock.The HBP concentration in the study group was significantly higher than that in the control group on the 1st day，and the HBP concentration in the group gradually decreased with the prolongation of hospital stay.The concentration of HBP on the first day of septic shock group was higher than that of sepsis group，and the difference was statistically significant（ P<0.001）.The concentration of HBP on the 1st day in the sepsis death group was significantly higher than that in the sepsis survival group（ P=0.023）.The receivor operator characteristic curve analysis showed that HBP and pSOFA had good predictive value for the death of children with sepsis，and the joint model of HBP and pSOFA（75.1×pSOFA-0.1×HBP）had the best predictive performance for the death of children with sepsis，but there was no significant difference with the pSOFA. Conclusion:The HBP level significantly increases in children with sepsis，and gradually decreases with the length of hospital stay，and HBP has great value in predicting the outcome of death in children with sepsis，and the combination of pSOFA could improve its predictive ability of death,but not better than pSOFA.