The surgical management of gastroesophageal reflux disease has evolved significantly with the increased understanding of the physiology of the reflux barrier. Initially, emphasis was on reduction of hiatal hernias and crural closure. With persistence of reflux symptoms, along with the development of esophageal manometry and the discovery of a high-pressure zone, focus evolved to surgical augmentation of the lower esophageal sphincter, including reconstruction of the angle of His, ensuring sufficient intra-abdominal esophageal length, fundoplication, and magnetic sphincter augmentation. More recently, the role of crural closure in antireflux and hiatal hernia repair has again received renewed attention due to the persistence of postoperative complications and recurrences. Rather than simply preventing transthoracic herniation of the fundoplication as was originally thought, crural closure has been documented to have a critical role in re-establishing intra-abdominal esophageal length and maintaining the pressure of LES. The application of mesh provides more options for strengthening crural closure. In this review, this article will discuss the evolution of surgical techniques for gastroesophageal reflux disease over the past century, aiming to better guide the surgical treatment and clinical research of gastroesophageal reflux disease.

Objective To investigate the effect of tumor-infiltrating B cells on the therapeutic efficacy of programmed death ligand-1[PD-(L)1]inhibitors and elucidate the potential mechanisms.Methods Based on immunotherapy cohorts for melanoma patients in public databases,the relationship of B cells with progression-free survival (PFS) and response to immune checkpoint inhibitors treatment was analyzed.TC-1 and B16-OVA cells were implanted subcutaneously and in the liver in 6-8-week-old female C57BL/6 mice to establish tumor xenograft models.The effect of B cell clearance on PD-(L)1 therapy was compared.Flow cytometry was performed on the 15th day of TC-1 tumor microenvironment (TME)to confirm the number,function and phenotypic changes of T cells.Flow cytometry and quantitative real-time polymerase chain reaction (qPCR)were used to detect B cell surface molecules and cytokines.Results Based on ERP105482 data from the ICBatlas public database,high CD19 expression in the tumors was associated with longer PFS in melanoma patients (753 vs 95 d,HR=0.3,95％CI:0.13～0.65,P=0.003).B cells were significantly enriched in immunotherapy-responsive patients (P=0.01).In a mouse TC-1 liver-loaded tumor model,PD-(L)1 antibody treatment reduced tumor mass (P<0.01),whereas B-cell clearance attenuated the therapeutic efficacy.B cells enhanced PD-(L)1 antibody treatment by promoting T cell infiltration and function,and the treatment resulted in changes in B cell subsets,as evidenced by an increase in PD-1 low-expressing subsets (P<0.01).Conclusion After PD-(L)1 treatment,a decrease in PD-1 expression on B cell subsets might be one of the potential mechanisms by which B cells enhance the efficacy of PD-(L)1 therapy.

Objective:To evaluate the relationship between preoperative serum albumin concentrations and postoperative delirium (POD) in the patients undergoing total knee/hip arthroplasty.Methods:Five hundred patients of both sexes, aged 50-90 yr, with body mass index of 50-80 kg, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective total knee or hip replacement under combined spinal-epidural anesthesia in our hospital from December 2021 to December 2022, were selected. Cerebrospinal fluid (CSF) samples were collected after successful subarachnoid puncture for determination of amyloid-beta 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) concentrations using enzyme-linked immunosorbent assay. Confusion Assessment Method and Memorial Delirium Assessment Scale were used to evaluate the occurrence and severity of POD at 1-7 days after surgery (or before discharge), and the patients were divided into POD group and non-POD group (NPOD group). Logistic regression analysis was used to identify the risk factors for POD. The accuracy of plasma albumin concentration and CSF biomarker concentration in predicting POD was evaluated by the receiver operating characteristic (ROC) curve, and the mediating effect of CSF biomarker was analyzed.Results:A total of 343 patients were finally enrolled in the study, and the incidence of POD was 23.3%. There were statistically significant differences in age, preoperative plasma albumin concentration and Memorial Delirium Assessment Scale score in POD group as compared with NPOD group ( P<0.05). Before and after adjusting for confounding factors, decreased plasma albumin and increased concentrations of P-tau and T-tau in CSF before operation were the risk factors for POD, and increased concentrations of Aβ42, Aβ42/P-tau and Aβ42/T-tau ratio in CSF were protective factors for POD. The area under the ROC curve of preoperative plasma albumin concentrations in predicting POD was 0.668, and the area under the ROC curve of preoperative plasma albumin concentrations combined with CSF biomarker concentrations in predicting POD was 0.810 ( P<0.05). The direct effect of plasma albumin on POD was -0.009 869 2, the total effect was 0.029 443 7, and the mediating effect of P-tau accounted for 33.53% of the total effect. Conclusions:Decreased preoperative plasma albumin concentration is a risk factor for POD, and P-Tau in CSF serves as a key mediator in the relationship between serum albumin concentrations and postoperative delirium in the patients undergoing total knee/hip arthroplasty.

Objective:To investigate the correlation between gamma-glutamyl transferase/high-density lipoprotein cholesterol ratio (GHR), neutrophil/lymphocyte ratio (NLR) and coronary heart disease (CHD), and evaluated its pathogenic risk and predictive value for CHD.Methods:A total of 694 patients admitted to our hospital from December 2017 to December 2018 for suspected CHD and coronary angiography were selected. According to the results of coronary angiography,the patients were divided into CHD group ( n=527) and non-CHD group ( n=167). The clinical data of all patients were recorded. Gamma-glutamyl transferase (GGT), high-density lipoprotein cholesterol (HDL-C) and other biochemical indicators were recorded. Neutrophils, lymphocyte count and other hematological indicators were recorded. GHR, NLR and Gensini scores of the patients were calculated. Clinical data and GHR, NLR and other indicators were compared between the two groups. Receiver operating characteristic curve (ROC) was used to evaluate the predictive value of GHR, NLR in CHD, and to determine the optimal cut-off value; Logstic regression analysis was used to investigate the risk factors of CHD.Spearman correlation analysis was used to analyze the correlation between serum OPN, OPG and Gensini score in patients with CHD. Results:The GHR and NLR were 32.59(21.05, 48.24) and 3.53(2.18, 8.46) significantly higher in the CHD group than in the non-CHD group 16.56(10.07, 25.21) and 2.20(1.45, 3.28) respectively, with statistically significant differences ( Z=11.094, 9.055, P<0.05). ROC curve analysis showed that the AUC of NLR and MLR in diagnosing CHD was 0.785 and 0.732( P<0.05). When the critical values of GHR and NLR respectively were 19.805 and 2.678, respectively, the diagnostic efficiency of CHD was the highest, and the sensitivity and specificity were 79.30%, 62.90% and 63.80%, 68.30%, and the AUC of GGT in diagnosing CHD was 0.628. When the critical value was 19.500, the sensitivity and specificity were 80.50% and 39.50%, respectively,the AUC of GHR was greater than that of GGT ( Z=12.973, P<0.05). Multivariate Logistic regression analysis showed that Smoking ( OR=2.887, 95% CI:1.850-4.505, P<0.05), hypertension ( OR=2.009, 95% CI: 1.311-3.080, P<0.05), fasting plasma glucose ( OR=1.109, 95% CI:1.034-1.189, P<0.05), age ≥60 years ( OR=1.567, 95% CI:1.179-2.415, P<0.05), NLR ≥2.687 ( OR=3.152, 95% CI:2.066-4.808, P<0.05) and GHR ≥19.805 ( OR=4.768, 95% CI:3.131-7.262, P<0.05) was an independent risk factor for CHD. After gradually adjustment for risk factors such as smoking, hypertensive, fasting plasma glucose, age ≥60 years and NLR ≥2.687, GHR ≥19.805 was still an independent risk factor for coronary heart disease(OR and 95% CI were 4.620 (3.049-7.000), 4.768 (3.131-7.262), 6.567 (4.408-9.810), 4.768 (3.131-7.262), 4.768 (3.131-7.262), respectively; all P<0.001). Spearman correlation analysis showed that GHR and NLR were positively correlated with Gensini score ( r=0.312, 0.394; all P<0.05). Conclusion:GHR and NLR were positively correlated with the severity of coronary artery disease, which is of significance in the diagnosis of coronary heart disease. NLR ≥2.687 and GHR ≥19.805 were independent risk factors for CHD. GHR was superior to GGT and HDL-C alone in the diagnosis of CHD,and has certain clinical application value

Objective To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma(OCCC)tissues and its clinical significance.Methods A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery(SCS),who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1) protein expression in paraffin-embedded tissues. Results The positive rates of EGFR, HER2, AURKA, BRCA1,BRCA2 and PD-L1 in primary and recurrent tumor tissues were respectively 20%(8/40)vs 30%(7/23),22%(9/40)vs 35%(8/23),38%(15/40)vs 35%(8/23),42%(17/40)vs 39%(9/23),20%(8/40)vs 22%(5/23), 25%(10/40)vs 17%(4/23), and there were no significant differences between primary and recurrent OCCC (all P>0.05). χ2-test or Fisher exact analysis revealed that HER2 expression in recurrent tumor tissues had a relationship with chemoresistance (P<0.05), while the expression of other biomarkers showed no significant relationship with chemoresistance (all P>0.05). Further, Kaplan-Meier survival analysis showed that patients with HER2 and AURKA-positive expression had a significantly shorter progression-free survival time in primary OCCC(4 months vs 10 months,log-rank test,P<0.05 for HER2;and 4 months vs 10 months,P<0.05 for AURKA);and a shorter overall survival time after SCS in recurrent OCCC (10 months vs 44 months, P<0.05 for HER2;and 13 months vs 43 months, P<0.05 for AURKA). However,multivariate Cox proportional hazards regression analysis indicated that none of these 6 biomarkers was independent risk factor of progression-free survival time of primary OCCC or overall survival time after SCS for recurrent OCCC (P>0.05). Conclusion HER2 and AURKA could serve as prognostic factors in ovarian clear cell carcinoma.

Background and purpose: Epithelial ovarian carcinoma is the most malignant tumor in female reproductive system because of its resistance to chemotherapy. Fructose-1, 6-bisphosphatase (FBP1) is a rate-limiting enzyme in gluconeogenesis used to catalyze the hydrolysis of fructose-1, 6-bisphosphate to fructose-6-phosphate and inorganic phosphate, thereby inhibiting the effect of glycolysis in tumor cells. This study aimed to investigate the association between the expression of FBP1 and chemosensitivity. Methods: The expression level of FBP1 in ovarian cancer patients was measured by immunohistochemistry. Results: According to the results of immunohistochemistry in 209 ovarian carcinoma specimens, the percentage of positive FBP1 expression was about 49.3% (103/209). Loss of FBP1 was a negative factor of survival (42.6 months vs 62.1 months, P=0.003). Besides, patients who were sensitive to chemotherapy displayed significantly higher scores of FBP1 expression than patients who were resistant to therapy (P=0.007). Conclusion: The rate-limiting enzyme FBP1 in gluconeogenesis can be used as a biomarker for predicting the chemoresistance and prognosis of ovarian cancer patients.

Background and purpose:Cervical cancer remains the second leading cause of death in gynecologic malignancies partially because of resistance to chemotherapy. Bufalin, a component of the traditional Chinese medicine Chansu, has been widely used in cancer treatment in China. This study aimed to investigate the effects of bufalin on inhibiting the proliferation of ME180 and C33A and explore its possible mechanism.Methods:The cytostatic effects of bufalin on ME180 and C33A cells were evaluated by CCK8 assay (cell counting kit-8). Glucose levels in ME180 and C33A cells were measured using glucose assay kit. Then the alterations of GLUT1 (glucose transporter 1) and HK2 (hexokinase 2) gene expression were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The expressions of proto-oncogene C-MYC and HIF1α (hypoxia-inducible factor 1α) were determined by Western blot.Results:According to the results of CCK-8, bufalin can significantly inhibit the proliferation of carcinoma cells ME180 and C33A (P=0.027,P=0.018). Test on glycometabolism indicated that glucose uptake in cells treated with bufalin decreased (P=0.034,P=0.036). Results from real-time PCR showed that the expression of glycometabolism related indicators GLUT1 (P=0.019) and HK2 (P=0.016) levels were signiifcantly down-regulated in bufalin treated group. Western blot showed that the expression of C-MYC and HIF1αin cells with bufalin treatment was down-regulated markedly.Conclusion:Bufalin can inhibit the proliferation of the cervical carcinoma cells ME180 and C33A through inhibition of their glucose metabolism.

ObjectiveTo explore the application value of low pressure flushing in minimally invasive percutaneous nephrolithotomy lithotripsy.MethodsClinical data of 38 patients,who adopted the low pressure flushing therapy for curing the renal or upper ureteral calculi in the percutaneous nephrostolithotomy lithotripsy were retrospectively arakyzed.ResultsAming 38 patients after operation,stone-free rate of stage 1 was obtained in 25 cases and the stones were completely removed after secondary operation in 2 cases.5 patients had partial residual stones and two cases were most of the residual stones.The mean operation time was 1 ～ 2.5h.The average duration of hospitalization was 8d.There were no intraoperative and postoperative complications,such as the spread of infection due to the surgery.ConclusionThe low pressure flushing could improve clinical efficacy of percutaneous nephrostolithotomy lithotripsy and it had high security.