The ataxia telangiectasia mutated(ATM)gene is an important tumor suppressor gene and a key effector gene in regulating the repair of double-strand DNA breaks.It plays an indispensable role in maintaining genetic stability,facilitating cell cycle arrest,and modulating cell apoptosis.When the ATM gene mutates,it fails to effectively induce the phosphorylation of downstream targets,leading to impaired DNA repair mechanisms,genetic instability,and chromosomal structural abnormalities,ultimately promoting abnormal proliferation of tumor cells.Analysis of next-generation sequencing(NGS)datas reveals a relatively high mutation rate of the ATM gene in bladder cancer cells.Relevant studies have shown that ATM gene regulates the proliferation,invasion,and metastasis of bladder cancer cells through the signaling pathways such as nuclear transcription factor-κB(NF-κB)and Interferon-γ(IFNγ).Mutanted ATM gene can enhance patients'sensitivity to radiotherapy and chemotherapy,and boost the efficacy of immunotherapy,resulting in a generally better prognosis for patients with ATM gene mutation.This finding marks ATM gene as a potential therapeutic target and predictive prognosis biomarker for bladder cancer patients.Therefore,this article will comprehensively review the research on the ATM gene in bladder cancer from 3 aspects:the structural characteristics of the ATM gene and its tumor-suppressing and tumor-promoting functions,the mechanism of action of the ATM gene in the occurrence and development of bladder cancer,and the impact of the ATM gene on the treatment and prognosis of bladder cancer patients.Additionally,the future research directions of the ATM gene was prospected,with the aim of providing new targets for the drug treatment of bladder cancer,and bringing new hope for the treatment of bladder cancer patients.

Ferroptosis is a form of iron dependent cell death,which is closely related to the progress and prognosis of bladder cancer(BCa).Among them,erroptosis related genes(FRGs)play an important role in the biological effects of BCa,such as participating in regulating the proliferation,migration,metastasis,drug resistance,immune regulation,and therapeutic efficacy of BCa cells.In addition,FRGs are also important biomarkers for predicting the prognosis of tumor patients.However,the specific mechanism of action of FRGs in BCa remains elusive.How to use FRGs to predict the prognosis of BCa and guide the treatment of BCa is still in the exploratory stage.Therefore,exploring the regulatory and predictive role of FRGs in BCa is particularly important for the diagnosis and treatment of BCa.This article aims to systematically elucidate the role of FRGs in the occurrence,development,treatment,and prognosis of BCa.To provide theoretical reference for further exploring the treatment of refractory and drug-resistant BCa patients,and constructing prognostic risk prediction models.

The ataxia telangiectasia mutated(ATM)gene is an important tumor suppressor gene and a key effector gene in regulating the repair of double-strand DNA breaks.It plays an indispensable role in maintaining genetic stability,facilitating cell cycle arrest,and modulating cell apoptosis.When the ATM gene mutates,it fails to effectively induce the phosphorylation of downstream targets,leading to impaired DNA repair mechanisms,genetic instability,and chromosomal structural abnormalities,ultimately promoting abnormal proliferation of tumor cells.Analysis of next-generation sequencing(NGS)datas reveals a relatively high mutation rate of the ATM gene in bladder cancer cells.Relevant studies have shown that ATM gene regulates the proliferation,invasion,and metastasis of bladder cancer cells through the signaling pathways such as nuclear transcription factor-κB(NF-κB)and Interferon-γ(IFNγ).Mutanted ATM gene can enhance patients'sensitivity to radiotherapy and chemotherapy,and boost the efficacy of immunotherapy,resulting in a generally better prognosis for patients with ATM gene mutation.This finding marks ATM gene as a potential therapeutic target and predictive prognosis biomarker for bladder cancer patients.Therefore,this article will comprehensively review the research on the ATM gene in bladder cancer from 3 aspects:the structural characteristics of the ATM gene and its tumor-suppressing and tumor-promoting functions,the mechanism of action of the ATM gene in the occurrence and development of bladder cancer,and the impact of the ATM gene on the treatment and prognosis of bladder cancer patients.Additionally,the future research directions of the ATM gene was prospected,with the aim of providing new targets for the drug treatment of bladder cancer,and bringing new hope for the treatment of bladder cancer patients.

Ferroptosis is a form of iron dependent cell death,which is closely related to the progress and prognosis of bladder cancer(BCa).Among them,erroptosis related genes(FRGs)play an important role in the biological effects of BCa,such as participating in regulating the proliferation,migration,metastasis,drug resistance,immune regulation,and therapeutic efficacy of BCa cells.In addition,FRGs are also important biomarkers for predicting the prognosis of tumor patients.However,the specific mechanism of action of FRGs in BCa remains elusive.How to use FRGs to predict the prognosis of BCa and guide the treatment of BCa is still in the exploratory stage.Therefore,exploring the regulatory and predictive role of FRGs in BCa is particularly important for the diagnosis and treatment of BCa.This article aims to systematically elucidate the role of FRGs in the occurrence,development,treatment,and prognosis of BCa.To provide theoretical reference for further exploring the treatment of refractory and drug-resistant BCa patients,and constructing prognostic risk prediction models.

BACKGROUND: Implantation of bone marrow mesenchymal stem cells (BMSCs) is a potential alternative for promoting bone defects healing or osseointegration in osteoporosis. However, the reactive oxygen species (ROS) accumulated and excessive inflammation in the osteoporotic microenvironment could weaken the self-replication and multi-directional differentiation of transplanted BMSCs. METHODS: In this study, to improve the hostile microenvironment in osteoporosis, Poloxamer 407 and hyaluronic acid (HA) was crosslinked to synthetize a thermos-responsive and injectable hydrogel to load MnO2 nanoparticles as a protective carrier (MnO2 @Pol/HA hydrogel) for delivering BMSCs. RESULTS: The resulting MnO2 @Pol/HA hydrogel processed excellent biocompatibility and durable retention time, and can eliminate accumulated ROS effectively, thereby protecting BMSCs from ROS-mediated inhibition of cell viability, including survival, proliferation, and osteogenic differentiation. In osteoporotic bone defects, implanting of this BMSCs incorporated MnO2 @Pol/HA hydrogel significantly eliminated ROS level in bone marrow and bone tissue, induced macrophages polarization from M1 to M2 phenotype, decreased the expression of pro-inflammatory cytokines (e.g., TNFa, IL-1b, and IL-6) and osteogenic related factors (e.g., TGF-b and PDGF). CONCLUSION This hydrogel-based BMSCs protected delivery strategy indicated better bone repair effect than BMSCs delivering or MnO2 @Pol/HA hydrogel implantation singly, which providing a potential alternative strategy for enhancing osteoporotic bone defects healing.

Objective:To investigate the strategy and feasibility of surgery for iatrogenic perforation of colorectum following colonoscopic examination or treatment.Methods:A retrospectively descriptive study was conducted. Twenty-one patients aged from 35 to 84 years old from the Department of General Surgery of the First Affiliated Hospital of Nanjing Medical University between Jan. 2015 and Dec. 2020 were enrolled in this study. There were 15 male and 6 female patients with a median age of 64 years.Observation indicators included patient demographics, including sex, age, comorbidity, abdominal surgical history; findings and outcomes of colonoscopy, including purpose of colonoscopy, time to the diagnosis of perforation; findings and outcomes of surgical treatment, including perforation site, perforation size, surgical methods, postoperative complications.Results:Eight patients were found with diagnostic colonoscopic perforation, 13 patients with therapeutic perforation (2 patients with endoscopic mucosal resection, 7 patients with endoscopic submucosal dissection and 4 patients with stent placement). Thirteen perforation occurred during the procedure of colonoscopy. Eleven patients with perforation occurred in the sigmoid colon, 3 in the ascending colon, 3 in the rectum, 2 in the descending colon, 1 in the cecum and 1 in the hepatic flexure. The perforation size ranged from 0.3 cm to 10.0 cm with a high likelihood of a bigger perforation occurred in diagnostic colonoscopy than therapeutic colonoscopy. Seven patients received primary surgical repair with 3 patients receiving diversion. Four patients received direct colostomy in the perforation site. Six patients received segmental colectomy or radical resection with primary anastomosis, among them 2 patients received defunctioning ileostomy. Four patients received resection with the Hartmann procedure. Nine patients were performed with laparoscopic surgery with 3 patients converted to open surgery. Six patients developed postoperative complications, including 1 bowel leakage, 2 wound infection, 1 wound infection accompanied with abdominal infection, 1 kidney infection. One patient with hepatic flexure perforation after stent placement died from septic shock after the Hartmann procedure.Conclusion:With proper indication, the performance of optimal surgical treatment will save lives of patients with colonoscopic perforation.

Objective:To investigate the clinical value of stylized laparoscopic hemicolec-tomy for left colon cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 174 patients who underwent laparoscopic hemicolectomy for left colon cancer in the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2020 were collected. There were 106 males and 68 females, aged 59(range, 17?86)years. All patients underwent stylized laparoscopic hemicolectomy for left colon cancer. Observation indicators: (1) surgical situations; (2) postoperative complications; (3) postoperative histopathological examinations; (4) follow-up. Follow-up was conducted using outpatient examination or telephone interview to detect tumor recurrence and metastasis and survival of patients up to October 2021. Follow-up was performed once every 3 months within postoperative 2 years, once every 6 months within postoperative 2 to 5 years and once a year after postoperative 5 years, with the end point as tumor recurrence and metastasis or death of patients. Measurement data with normal distribution were represented as Mean±SD and measurement data with skewed distribution were represented as M(range) or M( Q1, Q3). Count data were described as absolute numbers or percentages. Kaplan-Meier method was used to draw survival curve and calculate survival rate. Results:(1) Surgical situations. All the 174 patients underwent stylized laparoscopic hemicolectomy for left colon cancer successfully, including 6 cases receiving preoperative enteral stent placement due to bowel obstruc-tion, 3 cases receiving defunctioning ileostomy and 1 case receiving Hartmann procedure. The operation time, volume of intraoperative blood loss, time to postoperative initial defecation and duration of postoperative hospital stay of the 174 patients were 97(80,106)minutes, 45(25,60)mL, 5(3,6)days and 7(6,8)days, respectively. (2) Postoperative complications. Twelve of the 174 patients had complications, including 4 cases with incision infection or fat liquefaction, 3 cases with anastomotic leakage, 2 cases with incomplete bowel obstruction, 1 case with abdominal hemo-rrhage, 1 case with chylous leakage and 1 case with pulmonary infection. The 2 cases with anastomotic leakage underwent ileostomy. The patient with abdominal hemorrhage underwent laparotomy to stop bleeding. One elder patient died of postoperative pulmonary infection. The other patients with complications recovered with conservative treatment. (3) Postoperative histopatho-logical examinations. Of the 174 patients, there were 27 cases in stage Ⅰ of TNM staging, 68 cases in stage Ⅱ, 77 cases in stage Ⅲ and 2 cases in stage Ⅳ. There were 9 cases with well differentiated tumor, 107 cases with moderately differentiated tumor and 58 cases with poorly differentiated tumor. The number of lymph node detected, the number of positive lymph node and tumor diameter of the 174 patients were 19(15,23), 0(0,2) and 4(3,5)cm, respectively. Of the 174 patients, there were 79 cases with lymph node metastases, 21 cases with cancerous nodules, 35 cases with vascular invasion and 29 cases with nerve invasion. (4) Follow-up. Of the 174 patients, 157 cases were followed up for 27(range, 1?70)months. Of the 157 patients who conducted follow-up, 20 cases had tumor metastasis, including 9 cases with multiple metastasis, 5 cases with liver metastasis, 4 cases with lung metastasis, 1 case with bone metastasis and 1 case with spleen metastasis. The 5-year overall survival rate and tumor free survival rate of the 157 patients were 90.9% and 80.8%, respectively.Conclusion:The stylized laparoscopic hemicolectomy for left colon cancer is safe and feasible.

Objective:To investigate the efficacy and adverse effects of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing neutropenia in patients undergoing sequential adjuvant radiotherapy after postoperative chemotherapy for breast cancer.Methods:A total of 43 female patients with breast cancer from January 2017 to January 2019 in Shandong Cancer Hospital and Institute were analyzed prospectively. Twenty-one patients in the experimental group were given 6 mg of PEG-rhG-CSF subcutaneously 1-3 days before radiotherapy. In the control group, 22 patients were enrolled without PEG-rhG-CSF utilization. The lowest absolute neutrophil count (ANC), the number of days of radiotherapy interruption due to neutropenia, the number of recombinant human granulocyte colony-stimulating factor (rhG-CSF) used during radiotherapy and the occurrence of drug-induced skeletal muscle pain in the two groups were statistically analyzed.Results:No neutropenia fever was observed in the two groups during radiotherapy. In the experimental group, there was no case of grade Ⅲ neutropenia; while in the control group, there were 3 cases of grade Ⅲ neutropenia. The median value of the lowest ANC in the experimental group was 1.56×10 9/L, higher than that in the control group (1.37×10 9/L), with a statistically significant difference ( Z=-2.261, P=0.023). The median number of rhG-CSF used in the experimental group was 1, which was smaller than 2 in the control group, and the difference was statistically significant ( Z=-2.498, P=0.012). The median numbers of days of radiotherapy interruption due to neutropenia were 0 and 3 in the experimental group and the control group, with a statistically significant difference ( Z=-3.117, P=0.001). One case (4.8%) of drug-induced skeletal muscle pain was found in the experimental group and 5 cases (22.7%) in the control group, with no statistically significant difference ( χ2=1.586, P=0.208). Conclusion:PEG-rhG-CSF can effectively prevent neutropenia caused by radiotherapy after postoperative chemotherapy for patients with breast cancer, and can reduce the interruption of radiotherapy and the use of rhG-CSF during radiotherapy, which is helpful to the smooth process of radiotherapy.

Objective To analyze the risk factors for anastomotic leakage after low anterior resection(LAR) for rectal cancer.Methods The retrospective study of 1 336 patients with rectal cancer who underwent LAR from Jan.2013 to Dec.2017 in the Department of Colorectal Surgery,First Affiliated Hospital of Nanjing Medical University was conducted.There were 838 male and 498 female patients.The median age was 62 (53,70) years.Observation indicators:①intraoperative conditions,including the performance of preventive enterostomy,the preservation of left colic artery,the placement of transanal decompression tube;②postoperative conditions,for example,postoperative clinical symptoms and physical examination,postoperative hospital stay.Anastomotic leakage patients were graded according to the grading system of anastomotic leakage following anterior resection of the rectum proposed by the International Study Group of Rectal Cancer in 2010.Measurement data with non-normal distribution were described as median,and comparison between groups was done using Mann-Whitney U test.Ranked data were compared with rank sum test.Comparison of count data between groups were analyzed using the Chi-square test or Fisher exact test.Potential risk factors for anastomotic leakage were further analyzed with multiple logistic regression.Results Anastomotic leakage was noted in 138 (10.4％) of 1 336 patients with 93 patients (7.0％) of Grade B and 46 patients (3.4％) of Grade C respectively.The occurrence of Grade C anastomotic leakage was on the 3th day postoperatively,which was earlier than Grade B anastomotic leakage [5 (3,7) d,Z =2.746,P =0.006].There were significant differences in sex,BMI,placement of transanal decompression tube and tumor location between anastomotic leakage cases and non-anastomotic leakage cases by Chi-squared test (x2 =10.897,9.033,6.343,6.34,Z =-2.380,P ＜0.05).On multiple logistic regression analysis,male sex (OR =1.840,95 ％ CI:1.210-2.799,P =0.004),BMI ≥ 24 kg/m2 (OR =1.573,95 ％ CI:1.088-2.274,P =0.016),placement of transanal decompression tube(OR =2.418,95％ CI:1.196-4.888,P =0.014),middle rectal cancer (OR =1.536,95％ CI:O.836-2.822,P =0.167),low rectal cancer(OR =1.989,95％ CI:1.068-2.822,P =0.03),ultralow rectal cancer (OR =2.908,95％ CI:1.289-6.560,P =0.01) were independent risk factors of anastomotic leakage.Conclusion Male sex,high BMI,placement of transanal decompression tube and low rectal tumor were independent risk factors of anastomotic leakage for patients receiving LAR.

Objective To investigate the clinical effects of laparoscopic left colic artery (LCA) preserving total mesorectal excision (TME) for middle-low rectal cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 339 patients with middle-low rectal cancer who underwent laparoscopic TME in the First Affiliated Hospital of Nanjing Medical University from July 2016 to July 2017 were collected.There were 216 males and 123 females,aged from 35 to 89 years,with an average age of 62 years.No lymph node enlargement was detected at the root of inferior mesenteric artery as evaluated by preoperative examination.Of the 339 patients,173 undergoing laparoscopic TME with preservation of LCA and 166 without preservation of LCA were allocated into observation group and control group,respectively.Observation indicators:(1) surgical situations;(2) postoperative situations;(3) follow-up.Follow-up using outpatient examination and telephone interview was performed to detect complications and survival of patients after hospital discharge up to August 2018.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were described as M (range),and comparison between groups was analyzed using the Mann-Whitney U test.Count data were represented as absolute number or percentage,and comparison between groups was analyzed using the chi-square test or Fisher exact propability.Comparisons of ordinal data were analyzed by Mann-Whitney U test.Results (1) Surgical situations:339 patients underwent laparoscopic TME successfully,without conversion to open surgery or death.The operation time,volume of intraoperative blood loss and number of lymph nodes dissected at the root of inferior mesenteric artery were (77± 15)minutes,(32±22)mL and 3.5± 1.3 in the observation group,(74± 16)minutes,(30±21) mL and 3.6± 1.3 in the control group,respectively,showing no statistically significant difference between the two groups (t =1.730,0.790,-0.378,P＞0.05).There were 21 and 37 patients receiving preventive stoma in the observation group and control group,with a statistically significant difference between the two groups (x2 =6.154,P＜0.05).(2) Postoperative situations:no lymphatic metastasis at the root of inferior mesenteric artery was detected in the observation group or control group.The incidence of anastomotic leakage was 8.55％ (13/152) and 16.28％(21/129) of patients without preventive stoma in the observation group and control group,with a statistically significant difference between the two groups (x2=3.917,P＜0.05).The overall incidence of anastomotic leakage was 7.51％ (13/173) and 12.65％ (21/166),with no statistically significant difference between the two groups (x2 =2.477,P＞0.05).Cases with anastomotic hemorrhage and time to first anal sufflation were 18 and (2.2±0.9) days in the observation group,10 and (2.4±1.0) days in the control group,respectively,showing no statistically significant difference between the two groups (x2 =2.145,t =-1.370,P＞0.05).(3) Follow-up:339 patients were followed up for 13-22 months,with a median time of 14 months.During the follow-up,2 patients had postoperative intestinal obstruction,19 had tumor recurrence or metastasis,and 4 died in the observation group.In the control group,1 patient had postoperative intestinal obstruction,17 had tumor recurrence or metastasis,and 3 died.The other patients in the two groups survived well.Conclusion Laparoscopic TME with preservation of LCA can reduce incidence of anastomotic leakage in patients with middle-low rectal cancer who don't undergo preventive stoma.