The hypoxic microenvironment and inflammatory state of residual tumors caused by insufficient radio-frequency ablation(iRFA)are major reasons for rapid tumor progression and pose challenges for immu-notherapy.We retrospectively analyzed the clinical data of patients with hepatocellular carcinoma(HCC)treated with RFA and observed that iRFA was associated with poor survival outcomes and progression-free survival.Using an orthotopic HCC mouse model and a colorectal liver metastasis model,we observed that treatment with melatonin after iRFA reduced tumor growth and metastasis and achieved the best out-comes when combined with anti-programmed death-ligand 1(anti-PD-L1)therapy.In mechanism,melatonin inhibited the expression of epithelial-mesenchymal transitions,hypoxia-inducible factor(HIF)-1 α,and PD-L1 in tumor cells after iRFA.Flow cytometry revealed that melatonin reduced the proportion of myeloid-derived suppressor cells and increased the proportion of CD8+T cells.Transcriptomic analysis revealed an upregulation of immune-activated function-related genes in residual tumors.These findings demonstrated that melatonin can reverse hypoxia and iRFA-induced inflammation,thereby overcoming the immunosuppressive tumor microenvironment(TME)and enhancing the efficacy of immunotherapy.

Objective:In this study, we aimed to compare the short-term safety of two digestive tract reconstruction techniques, laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis, following radical resection of Siewert Type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 139 patients who had undergone radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. These included 89 patients treated at the First Affiliated Hospital of Air Force Medical University from November 2021 to July 2023, 36 patients treated at the First Affiliated Hospital of Xi'an Jiaotong University from December 2020 to June 2021, and 14 patients treated at the Yuncheng Central Hospital in Shanxi Province from September 2021 to November 2022. The group consisted of 107 men (77.0%) and 32 women (23.0%) of mean age 62.5±9.3 years. Forty-eight patients underwent laparoscopic total abdominal overlap anastomosis (overlap group), and 91 laparoscopic-assisted end-to-side anastomosis (end-to-side group). Clinical data, surgical information, pathological findings, postoperative recovery, and related complications were compared between the two groups.Results:There were no significant differences in general clinical data between the overlap and end-to-side anastomosis groups (all P>0.05), indicating comparability. There was no significant difference in operation time (267.2±60.1 minutes vs. 262.8±70.6 minutes, t=0.370, P=0.712). However, the intraoperative blood loss in the overlap group (100 [50, 100] mL) was significantly lower compared to the end-to-side group (100[50, 175] mL, Z=2.776, P=0.005). Compared to the end-to-side group, longer distances between the tumor and distal resection margin proximal(1.7±1.0 cm vs. 1.3±0.9 cm, t=2.487, P=0.014) and the tumor and distal resection margin (9.5±2.9 cm vs. 7.9±3.5 cm, t=2.667, P=0.009) were achieved in the overlap group. Compared with the end-to-side group, the overlap group achieved significantly earlier postoperative ambulation (1.0 [1.0, 2.0] days vs. 2.0 [1.0, 3.0] days, Z=3.117, P=0.002), earlier time to first drink (4.7±2.6 days vs. 6.2±3.0 days, t=2.851, P=0.005), and earlier time to first meal (6.0±2.7 days vs. 7.1±3.0 days, t=2.170, P=0.032). However, the hospitalization costs were higher in the overlap group (113, 105.5±37, 766.3) yuan vs. (97, 250.2±27, 746.9) yuan; this difference is significant ( t=2.818, P=0.006). There were no significant differences between the two groups in postoperative hospital stay, total number of lymph nodes cleared, or time to first postoperative flatus (all P>0.05). The incidence of surgery-related complications was 22.9%(11/48) in the overlap group and 19.8% (18/91) in the end-to-side group; this difference is not significant (χ2=0.187, P=0.831). Further comparison of complications using the Clavien-Dindo classification also showed no significant differences ( Z=0.406, P=0.685). Conclusions:Both laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis are feasible for radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. Laparoscopic total abdominal overlap anastomosis achieves longer proximal and distal resection margins and better postoperative recovery; however, end-to-side anastomosis is more cost-effective.

Objective:In this study, we aimed to compare the short-term safety of two digestive tract reconstruction techniques, laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis, following radical resection of Siewert Type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 139 patients who had undergone radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. These included 89 patients treated at the First Affiliated Hospital of Air Force Medical University from November 2021 to July 2023, 36 patients treated at the First Affiliated Hospital of Xi'an Jiaotong University from December 2020 to June 2021, and 14 patients treated at the Yuncheng Central Hospital in Shanxi Province from September 2021 to November 2022. The group consisted of 107 men (77.0%) and 32 women (23.0%) of mean age 62.5±9.3 years. Forty-eight patients underwent laparoscopic total abdominal overlap anastomosis (overlap group), and 91 laparoscopic-assisted end-to-side anastomosis (end-to-side group). Clinical data, surgical information, pathological findings, postoperative recovery, and related complications were compared between the two groups.Results:There were no significant differences in general clinical data between the overlap and end-to-side anastomosis groups (all P>0.05), indicating comparability. There was no significant difference in operation time (267.2±60.1 minutes vs. 262.8±70.6 minutes, t=0.370, P=0.712). However, the intraoperative blood loss in the overlap group (100 [50, 100] mL) was significantly lower compared to the end-to-side group (100[50, 175] mL, Z=2.776, P=0.005). Compared to the end-to-side group, longer distances between the tumor and distal resection margin proximal(1.7±1.0 cm vs. 1.3±0.9 cm, t=2.487, P=0.014) and the tumor and distal resection margin (9.5±2.9 cm vs. 7.9±3.5 cm, t=2.667, P=0.009) were achieved in the overlap group. Compared with the end-to-side group, the overlap group achieved significantly earlier postoperative ambulation (1.0 [1.0, 2.0] days vs. 2.0 [1.0, 3.0] days, Z=3.117, P=0.002), earlier time to first drink (4.7±2.6 days vs. 6.2±3.0 days, t=2.851, P=0.005), and earlier time to first meal (6.0±2.7 days vs. 7.1±3.0 days, t=2.170, P=0.032). However, the hospitalization costs were higher in the overlap group (113, 105.5±37, 766.3) yuan vs. (97, 250.2±27, 746.9) yuan; this difference is significant ( t=2.818, P=0.006). There were no significant differences between the two groups in postoperative hospital stay, total number of lymph nodes cleared, or time to first postoperative flatus (all P>0.05). The incidence of surgery-related complications was 22.9%(11/48) in the overlap group and 19.8% (18/91) in the end-to-side group; this difference is not significant (χ2=0.187, P=0.831). Further comparison of complications using the Clavien-Dindo classification also showed no significant differences ( Z=0.406, P=0.685). Conclusions:Both laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis are feasible for radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. Laparoscopic total abdominal overlap anastomosis achieves longer proximal and distal resection margins and better postoperative recovery; however, end-to-side anastomosis is more cost-effective.

Odontoblasts are primarily responsible for synthesizing and secreting extracellular matrix proteins,which are crucial for dentinogenesis.Our previous single-cell profile and RNAscope for odontoblast lineage revealed that cyclic adenosine monophosphate responsive element-binding protein 3 like 1(Creb3l1)was specifically enriched in the terminal differentiated odontoblasts.In this study,deletion of Creb3l1 in the Wnt1+lineage led to insufficient root elongation and dentin deposition.Assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)and RNA sequencing were performed to revealed that in CREB3L1-deficient mouse dental papilla cells(mDPCs),the genes near the closed chromatin regions were mainly associated with mesenchymal development and the downregulated genes were primarily related to biological processes including cell differentiation,protein biosynthesis and transport,all of which were evidenced by a diminished ability of odontoblastic differentiation,a significant reduction in intracellular proteins,and an even greater decline in extracellular supernatant proteins.Dentin matrix protein 1(Dmp1),dentin sialophosphoprotein(Dspp),and transmembrane protein 30B(Tmem30b)were identified as direct transcriptional regulatory targets.TMEM30B was intensively expressed in the differentiated odontoblasts,and exhibited a significant decline in both CREB3L1-deficient odontoblasts in vivo and in vitro.Deletion of Tmem30b impaired the ability of odontoblastic differentiation,protein synthesis,and protein secretion in mDPCs.Moreover,overexpressing TMEM30B in CREB3L1-deficient mDPCs partially rescued the extracellular proteins secretion.Collectively,our findings suggest that CREB3L1 participates in dentinogenesis and facilitates odontoblastic differentiation by directly enhancing the transcription of Dmp1,Dspp,and other differentiation-related genes and indirectly promoting protein secretion partially via TMEM30B.

Odontoblasts are primarily responsible for synthesizing and secreting extracellular matrix proteins,which are crucial for dentinogenesis.Our previous single-cell profile and RNAscope for odontoblast lineage revealed that cyclic adenosine monophosphate responsive element-binding protein 3 like 1(Creb3l1)was specifically enriched in the terminal differentiated odontoblasts.In this study,deletion of Creb3l1 in the Wnt1+lineage led to insufficient root elongation and dentin deposition.Assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)and RNA sequencing were performed to revealed that in CREB3L1-deficient mouse dental papilla cells(mDPCs),the genes near the closed chromatin regions were mainly associated with mesenchymal development and the downregulated genes were primarily related to biological processes including cell differentiation,protein biosynthesis and transport,all of which were evidenced by a diminished ability of odontoblastic differentiation,a significant reduction in intracellular proteins,and an even greater decline in extracellular supernatant proteins.Dentin matrix protein 1(Dmp1),dentin sialophosphoprotein(Dspp),and transmembrane protein 30B(Tmem30b)were identified as direct transcriptional regulatory targets.TMEM30B was intensively expressed in the differentiated odontoblasts,and exhibited a significant decline in both CREB3L1-deficient odontoblasts in vivo and in vitro.Deletion of Tmem30b impaired the ability of odontoblastic differentiation,protein synthesis,and protein secretion in mDPCs.Moreover,overexpressing TMEM30B in CREB3L1-deficient mDPCs partially rescued the extracellular proteins secretion.Collectively,our findings suggest that CREB3L1 participates in dentinogenesis and facilitates odontoblastic differentiation by directly enhancing the transcription of Dmp1,Dspp,and other differentiation-related genes and indirectly promoting protein secretion partially via TMEM30B.

Objective:To monitor the epidemiological characteristics of viral etiology in children with influenza-like illness and to guide the prevention and management of acute respiratory tract infections in childhood.Methods:Nasopharyngeal swabs were collected from the outpatient children seeking medical care in Children′s Hospital of Fudan University, Shanghai for influenza-like illness between January 2015 and December 2018. Multiplex real-time polymerase chain reaction was performed to detect respiratory syncytial virus (RSV), influenza virus (Flu), adenovirus (ADV), parainfluenza virus (PIV, type Ⅰ to type Ⅳ) and enterovirus (EV), and the epidemiological data were analyzed. Chi-square test was used for statistical analysis.Results:A total of 2 271 patients with influenza-like illness were enrolled, age range from two months to 182 months old, 1 280 cases(56.4%) were positive for the target respiratory viruses tested on respiratory samples. The detection rates of FluA, FluB, PIV, EV, ADV, RSV were 15.1%(343/2 271), 12.5%(284/2 271), 8.4%(191/2 271), 7.8%(177/2 271), 5.1%(116/2 271) and 6.7%(152/2 271), respectively.The detection rates of influenza virus were statistically different among the age groups ( χ2=39.33, P<0.05), which showed an increasing trend with the increasing ages. The detection rate of RSV was 9.7%(35/361) in infant group from zero to 12 months old, which was higher than other age groups. Usually, FluA had two epidemic peaks during the winter and summer seasons, the epidemics of FluB and RSV peaked during the winter season, and EV and PIV were more prevalent in the summer season. Conclusions:Influenza virus remains the most common viral pathogen responsible for childhood influenza-like illness in Shanghai.Influenza virus has high incidence in winter.Widely influenza vaccination is highly recommended for the effective prevention the influenza outbreaks.Continuous monitoring the epidemic trend of viral respiratory infections is imperative for the prevention and control of diseases.

Objective To evaluate the clinical value of prenatal ultrasound in the diagnosis of congenital anal atresia.Methods A retrospective analysis was studied from January 2013 to December 2015 which analyzed abnormal sonographic features by prenatal ultrasound screening in 13 cases of anal atresia.Results 13 cases of anal atresia were confirmed after abortion,miscarriage or birth which were not probed target ring signby prenatal ultrasound screening.That included 2 simple atresia cases and 11 cases associated with other malformations and abnormalities including 8 cases with bowel dilatation and 3 cases with intestine visible echogenic meconium. Conclusion Prenatal ultrasound screening for fetal congenital anal atresia can be detected.But for lacking of specific diagnostic standard,the detection rate of anal atresia remains very low.

OBJECTIVETo compare the survival rate of proximal gastrectomy and total gastrectomy in the treatment of esophagogastric junction (EGJ) adenocarcinoma (Siewert II( types), and to provide reference for clinical choice.

METHODSA total of 533 patients with Siewet II( type EGJ adenocarcinoma were screened. All the patients underwent radical operations and were pathologically diagnosed as Siewet II( type EGJ adenocarcinoma in Xijing Hospital of Digestive Diseases from May 2008 to March 2014. These patients all had complete followed-up data. Finally, 234 patients were enrolled into the retrospective study, and divided into proximal gastrectomy group(117 patients) and total gastrectomy group (117 patients) based on the matching of age, sex, tumor size, TNM staging, and differentiation. The survival rate was compared between the two groups.

RESULTSIn proximal gastrectomy and total gastrectomy group, the overall 3-year survival rate was 65.6% and 62.6% respectively, and the overall 5-year survival rate was 53.8% and 44.5% respectively. No significant difference was found between the two groups (P=0.768). In subgroup analyses of 3-year survival rate between proximal gastrectomy group and total gastrectomy group, the results were as follows: 72.8% and 80.4% respectively (P=0.423) for tumor diameter ≤4 cm, 57.9% and 46.5% (P=0.239) for tumor diameter >4 cm, 83.3% and 83.3% (P=0.998) for high differentiated EGJ adenocarcinoma, 68.2% and 53.3% (P=0.270) for moderate differentiated EGJ adenocarcinoma, 56.1% and 69.6% (P=0.280) for poorly differentiated EGJ adenocarcinoma, 64.8% and 56.0% (P=0.451) for mucinous EGJ adenocarcinoma, 80.0% and 76.9% (P=0.912) for T1-2 stage EGJ adenocarcinoma, 64.3% and 60.4% (P=0.610) for T3 stage, 50.0% and 62.5% (P=0.953) for T4a stage, 92.3% and 100% (P=0.380) for stage I( EGJ adenocarcinoma, 79.6% and 66.3%(P=0.172) for stage II(, 42.6% and 49.5% (P=0.626) for stage I I(. All above differences between the two groups were not significant(all P>0.05).

CONCLUSIONProximal gastrectomy and total gastrectomy are comparable in terms of 3-year and 5-year survival rates.

Adenocarcinoma ; diagnosis ; surgery ; Esophageal Neoplasms ; diagnosis ; surgery ; Esophagogastric Junction ; pathology ; surgery ; Gastrectomy ; Humans ; Neoplasm Staging ; Retrospective Studies ; Stomach Neoplasms ; diagnosis ; surgery ; Survival Rate

OBJECTIVETo investigate the survival benefit of cytoreductive surgery in gastric cancer patients with peritoneal metastasis.

METHODSClinicopathological data of 151 advanced gastric adenocarcinoma patients with extensive peritoneal metastasis who were identified by surgical exploration between May 2008 and April 2015 in Xijing Hospital of Digestive Diseases were analyzed retrospectively. Of all the patients, 32 cases were treated by cytoreductive surgery with local radical tumor resection and regional lymph node cleaning, combined with fluorouracil-based adjuvant chemotherapy after surgery (cytoreductive surgery combined with chemotherapy group); 39 caseswere only treated by cytoreductive surgery group(cytoreductive surgery group);23 caseswere treated bysurgical exploration combined with fluorouracil-based adjuvant chemotherapy after surgery(surgical exploration combined with chemotherapy group) and 57 cases were only treated bysurgical exploration (surgical exploration group). The overall survival of four groups were analyzed and compared.

RESULTSAmong the 151 patients, 148 (98.0%) patients were followed up. The median follow up time was 7.2 months (range 1.4-61.2). The median survival of cytoreductive surgery combined with chemotherapy group, cytoreductive surgery group, surgical exploration combined with chemotherapy group and surgical exploration group was 11.9(95% CI: 8.8-15.1) months, 7.1(95% CI: 3.2-11.1) months, 8.2(95% CI:4.6-11.8) and 5.4(95% CI:4.4-6.4) months, respectively(P < 0.01).

CONCLUSIONSCytoreductive surgery can prolong the survival of gastric adenocarcinoma patients with extensive peritoneal metastasis. Cytoreductive surgery combined with chemotherapy may provide more benefit for patients, and can be used as a choice of treatment in these patients.

Adenocarcinoma ; Antineoplastic Combined Chemotherapy Protocols ; Chemotherapy, Adjuvant ; Cytoreduction Surgical Procedures ; Humans ; Lymph Nodes ; Peritoneal Neoplasms ; secondary ; Retrospective Studies ; Stomach Neoplasms

OBJECTIVETo compare the long-term survival and postoperative complications of distal gastric cancer patients between Billroth I((BI() and Billroth II((BII() reconstruction.

METHODSClinicopathological data of 992 patients with distal gastric cancer who underwent D2 curative gastrectomy in our department from May 2008 to April 2015 were recorded, including 207 patients of BI( reconstruction and 785 of BII( reconstruction, were retrospectively analyzed. Patients presenting a previous history of cancer, gastric resection or cytotoxic chemotherapy, and those presenting liver or intraperitoneal tumor dissemination or unresectable infiltration into contiguous organs were excluded. Patients in BI( and BII( group were selected using gmatch methods based on age (±10 years), gender, tumor size (±1 cm), differentiated degree and depth of invasion in order to reduce the selection bias of clinicopathological characteristics. The final number of patients matched was 191 respectively.

RESULTSCompared with BII( group, the BI( group had a significantly shorter operation time (181.7 min vs. 220.7 min, P=0.000) and a shorter postoperative hospitalization stay (7.6 days vs. 8.1 days, P=0.046). The postoperative complications including anastomotic leakage, wound dehiscence, wound infection, intraperitoneal hemorrhage, intestinal obstruction, duodenal stump fistula, pulmonary infection and fever had no significant difference(P>0.05). Three-year survival between two groups was comparable (82.9% vs. 78.7%, P=0.379).

CONCLUSIONSCompared with BII(, BI( reconstruction is more suitable for patients with distal gastric cancer.

Gastrectomy ; Gastroenterostomy ; Humans ; Postoperative Complications ; Postoperative Period ; Retrospective Studies ; Stomach Neoplasms ; surgery