AIM:To compare the efficacy and safety of early combination therapy with ranibizumab and dexamethasone intravitreal implants versus ranibizumab monotherapy for the treatment of macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: A retrospective cohort study was conducted on a total of 62 cases(64 eyes)of patients who were first diagnosed with RVO-ME at the Eye Centre of the Affiliated Hospital of Shandong Second Medical University between February 2022 and February 2023. The subjects were divided into two groups according to the different treatment regimens: 32 cases(34 eyes)in the monotherapy group received only ranibizumab [3+pro re nata(PRN)regimen], and 30 cases(30 eyes)in the combination therapy group were injected with ranibizumab once first, followed by dexamethasone intravitreal implant 3 wk later(1+DEX regimen). The best corrected visual acuity(BCVA), central retina thickness(CRT), foveal avascular zone(FAZ)area, macular vascular density(MVD)at the level of the deep vascular complex(DVC)of the retina, the incidence of ocular adverse effects, the number of drug injections, and the total cost between the two groups were compared before and after treatment.RESULTS: At 3 wk, 3 and 6 mo, and at the final follow-up of the two groups of patients, the improvement in BCVA, CRT, and MVD in the DVC layer was significantly better than that before treatment(all P<0.05); there were differences in the comparisons of BCVA and CRT between the two groups at 6 mo and the final follow-up(all P<0.05), and the increase in the number of letters of BCVA was the most pronounced in the combination therapy group at 6 mo of treatment. Statistical significant difference was observed in the comparison of MVD in the DVC layer between the two groups at 3 and 6 mo after treatment and at the final follow-up(all P<0.05). However, no significant change in FAZ area was evident before and after treatment in both groups(P>0.05). The combination therapy group exhibited a reduced number of injections and total cost in comparison to the monotherapy group. The combination therapy group exhibited a slightly higher incidence of high intraocular pressure and cataract progression compared to the monotherapy group, with no statistical significant difference(all P>0.05). Furthermore, no serious adverse events were observed in either group following treatment.CONCLUSION:Compared with ranibizumab alone, ranibizumab combined with dexamethasone intravitreal implant significantly improved vision, reduced macular edema, and lowered the frequency of injections and total treatment cost in patients with RVO-ME. CRT and MVD in the DVC layer are reliable prognostic indicators for patients with RVO-ME.

BACKGROUND: Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China. METHODS: Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate. RESULTS: Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P  <0.05). CONCLUSIONS: This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics. REGISTRATION ClinicalTrials.gov , NCT03484806.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Heart Valve Diseases/therapy* ; Kaplan-Meier Estimate ; Tertiary Care Centers ; Treatment Outcome

OBJECTIVES: To create a mixed valvular heart disease (MVHD)-related age-adjusted comorbidity index (MVACI) model for predicting mortality risk of patients with MVHD. METHODS: A total of 4080 patients with moderate or severe MVHD in the China-VHD study were included. The primary endpoint was 2-year all-cause mortality. A MVACI model prediction model was constructed based on the mortality risk factors identified by univariate and multivariate Cox regression analysis. Restricted cubic splines were used to assess the relationship between MVACI scores and 2-year all-cause mortality. The optimal threshold, determined by the maximum Youden index from receiver operator characteristic (ROC) curve analysis, was used to stratify patients. Kaplan-Meier method was used to calculate 2-year all-cause mortality and compared using the Log-rank test. Univariate and multivariate Cox proportional hazards models were employed to calculate hazard ratios (HR) and 95% confidence intervals (CI), evaluating the association between MVACI scores and mortality. Paired ROC curves were used to compare the discriminative ability of MVACI scores with the European System for Cardiac Operative Risk Evaluation Ⅱ(EuroSCORE Ⅱ) or the age-adjusted Charlson comorbidity index (ACCI) in predicting 2-year clinical outcomes, while calibration curves assessed the calibration of these models. Internal validation was performed using the Bootstrap method. Subgroup analyses were conducted based on etiology, treatment strategies, and disease severity. RESULTS: Multivariate analysis identified the following variables independently associated with 2-year all-cause mortality in patients: pulmonary hypertension, myocardiopathy, heart failure, low body weight (body mass index <18.5 kg/m²), anaemia, hypoalbuminemia, renal insufficiency, cancer, New York Heart Association (NYHA) class and age. The score was independently associated with the risk of all-cause mortality, and exhibited good discrimination (AUC=0.777, 95%CI: 0.755-0.799) and calibration (Brier score 0.062), with significantly better predictive performance than EuroSCORE Ⅱ or ACCI (both adjusted P<0.01). The internal validation showed that the MVACI model's predicted probability of 2-year all-cause mortality was generally consistent with the actual probability. The AUCs for predicting all-cause mortality risk were all above 0.750, and those for predicting adverse events were all above 0.630. The prognostic value of the score remained consistent in patients regardless of their etiology, therapeutic option, and disease severity. CONCLUSIONS The MVACI was constructed in this study based on age and comorbidities, and can be used for mortality risk prediction and risk stratification of MVHD patients. It is a simple algorithmic index and easy to use.
Humans ; Prognosis ; Comorbidity ; Heart Valve Diseases/epidemiology* ; Female ; Male ; Middle Aged ; Aged ; Proportional Hazards Models ; Risk Factors ; China/epidemiology* ; Age Factors ; Risk Assessment ; Adult ; ROC Curve

In recent years, with the continuous development of biotechnology, liquid biopsy techno-logy has gradually become a research hotspot in the field of tumor research. As a non-invasive diagnostic method, liquid biopsy has great advantages compared with traditional methods. The liquid biopsy technology is precise, convenient, non-invasive and safe, and has an increasingly important clinical significance in the early diagnosis, treatment and prognosis assessment of esophageal squamous cell carcinoma.

Reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2) acts as a source of reactive oxygen species, which participates in and influences normal physiological function of human body. Nowadays, many studies have found that Nox2 is related to prognosis of patients, drug resistance and molecular targeted therapy in various malignant tumors, such as acute myeloid leukemia, gastric cancer, colorectal cancer, ovarian cancer, lung cancer and esophageal cancer. What's more, it may be a novel biomarker and a potential therapeutic target for malignant tumors.

As a transport channel for amino acids, solute carrier (SLC) exists in all kinds of cells, and its function is to transport various amino acids and provide necessary nutrients for the growth and development of cells. In recent years, SLC7A5 and SLC7A11 genes of SLC7 family members have been found to be highly expressed in various malignant tumors, which can promote the occurrence and development of tumors by providing necessary amino acids for tumors. Studies have shown that these genes are associated with a variety of malignant tumors, and their expression is closely related to the growth, metastasis, treatment and prognosis of tumor cells. Moreover, the results of multiple studies suggest that SLC7A5 and SLC7A11 genes can be used as therapeutic targets for malignant tumors. Clarifying the expression and clinical significance of the above genes in malignant tumors, the molecular biological mechanism and the progress of molecular targeted therapy are helpful to provide a new way for the diagnosis and treatment of malignant tumors.

Objective To analyze the characteristics of the muscle strength around the knee joint of chondromalacia patellae patients, and to explore the difference with normal people.Methods In March, 2021, 70 knee-onset chondromalacia patellae patients (experimental group) and 35 normal people (control group) were measured isokinetic muscle strength of flexion and extension of knee in angular velocities of 60°/s and 180°/s.Results At 60°/s and 180°/s, the peak torque, the peak torque-to-weight ratio and the total work of the flexor and extensor muscles on the affected side in the experimental group were lower than that of the control group (U > 1097.0, P<0.001). The peak torque, the peak torque-to-weight ratio and the total work of the flexor and extensor muscles at 60°/s and extensor muscles at 180°/s were lower on the affected side than on the healthy side in the experimental group (|Z| > 2.121, P<0.05). The peak torque ratios at 60°/s and 180°/s were more in the affected knees than in the healthy knees of experimental group and in the control group (U > 1810.0, |Z| >3.691, P<0.01).Conclusion The explosive force and endurance of the knee flexor and extensor has weakened in patients with chondromalacia patellae, and there is imbalance in knee joint muscle strength.

Objective:To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients.Methods:A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m 2) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results:Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%).Conclusions:The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m 2) plus S-1 regimen for 2 weeks. However, it′s still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.

Objective:To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients.Methods:A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m 2) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results:Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%).Conclusions:The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m 2) plus S-1 regimen for 2 weeks. However, it′s still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.

Objective:To intestigate the clinical efficacy between modified Overlap anastomosis and traditional auxiliary incision anastomosis in laparoscopic total gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 115 patients with gastric cancer who were admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to December 2018 were collected. There were 62 males and 53 females, aged from 27 to 83 years, with a median age of 62 years. Of 115 patients, 51 patients undergoing totally laparoscopic total gastrectomy with modified Overlap anastomosis using linear stapler were divided into modified Overlap group and 64 patients undergoing laparoscopic assisted total gastrectomy with traditional auxiliary incision anastomosis using circular stapler were divided into traditional assisted group. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) anastomotic complications; (4) follow-up. Follow-up using outpatient examination or telephone interview was conducted to detected tumor recurrence and survival of patients up to December 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ranked data was analyzed using the rank sum test. Results:(1) Surgical situations: the operation time, time of esophagojejunostomy, volume of intraoperative blood loss, the number of lymph node dissected, length of proximal incisional margin and length of auxiliary incision of the modified Overlap group were (234.0±11.0)minutes, (29.4±2.1)minutes, (53±14)mL, 42±13, (2.0±0.3)cm and (5.1±0.4)cm, respectively. The above indicators of the traditional assisted group were (231.0±11.0)minutes, (29.2±2.2)minutes, (50±13)mL, 40±10, (2.2±0.4)cm and (8.2±0.4)cm, respectively. There was significant difference in the length of auxiliary incision between the two groups ( t=-43.098, P<0.05), and there was no significant difference in the operation time, time of esophagojejunostomy, volume of intraoperative blood loss, the number of lymph node dissected, length of proximal incisional margin between the two groups ( t=1.168, 0.460, 0.990, 1.127, -1.926, P>0.05). (2) Postoperative situations: cases with mild, moderate, severe pain (postoperative pain degree), time to first flatus, time to initial fluid diet intake, duration of postoperative hospital stay of the modified Overlap group were 40, 9, 2, (2.9±1.0)days, (4.8±2.2)days, (11.7±2.8)days, respectively. The above indicators of the traditional assisted group were 31, 27, 6, (3.9±1.4)days, (6.5±2.5)days, (13.0±3.1)days, respectively. There were significant differences in the above indicators between the two groups ( Z=-3.217, t= -4.344, -3.888, -2.261, P<0.05). (3) Anastomotic complications: cases with anastomotic leakage, cases with anastomotic bleeding, cases with anastomotic stenosis of the modified Overlap group were 1, 1, 0, respectively. The above indicators of the traditional assisted group were all 1. There was no significant difference in the above indicators between the two groups ( P>0.05). Cases with anastomotic leakage were cured after the treatment of enteral nutritional support through nasogastric catheterization, which were confirmed by gastroenterography. Cases with anastomotic bleeding were improved by active hemostatic therapy. Cases with anastomotic stenosis were improved after the symptomatic treatment of anti-inflammatory and anti-swelling. (4) Follow-up: 109 of the 115 patients were followed up. Forty-eight of 51 patients in the modified Overlap group were followed up for 15.0-45.0 months, with a median follow-up time of 33.5 months. Sixty-one of 64 patients in the traditional assisted group were followed up for 16.0-46.0 months, with a median follow-up time of 27.0 months. There was no tumor recurrence in the modified Overlap group. One patient in the traditional assisted group had tumor recurrence with liver metastasis and survived with tumor. There was no significant difference in tumor recurrence rate between the two groups ( P>0.05). There was no patient died during the follow-up. Conclusion:Compared with traditional auxiliary incision anastomosis, patients undergoing total laparoscopic total gastrectomy with modified Overlap anastomosis have small incision, good postoperative recovery.