[Longdan Xiegan Decoction and its interpretation from the perspective of meridians].

By systematically examing through Longdan Xiegan Decoction in medical books of the past dynasties, it was found that the Longdan Xiegan Decoction recorded in Lan Shi Mi Cang mainly targeted men's genital odor at frist. After Xue Ji's addition and subtraction, the scope of the prescription was gradually generalized and expanded, and confusion its name, composition and source of the prescription appeared, which was particularly prominent in Jingyue Quanshu and Yifang Jijie.Doctors used to interpret this prescription from the perspective of viscera. In order to better understand the main treatment rules of Longdan Xiegan Decoction, it is necessary to change the perspective and reinterpreted it from the perspective of meridians.Attributing the symptoms of the perineum to Liver Meridian of Foot-Jueyin,hypochondriac pain, deafness and other symptoms to the Gallbladder Meridian of Foot-Shaoyang, and adding or subtracting herbs according to the specific conditions, is not only conducive to a comprehensive and in-depth understanding of the prescription to achieve accurate clinical syndrome differentiation and medication, but also prompts modern researchers to rethink the important role of meridian theory in the formation and development of the theoretical system of traditional Chinese medicine.

Tislelizumab versus chemotherapy as second-line treatment for European and North American patients with advanced or metastatic esophageal squamous cell carcinoma: a subgroup analysis of the randomized phase III RATIONALE-302 study.

BACKGROUND: The phase III RATIONALE-302 study evaluated tislelizumab, an anti-programmed cell death protein 1 antibody, as second-line (2L) treatment for advanced/metastatic esophageal squamous cell carcinoma (ESCC). This prespecified exploratory analysis investigated outcomes in patients from Europe and North America (Europe/North America subgroup). PATIENTS AND METHODS: Patients with tumor progression during/after first-line systemic treatment were randomized 1 : 1 to open-label tislelizumab or investigator's choice of chemotherapy (paclitaxel, docetaxel, or irinotecan). RESULTS: The Europe/North America subgroup comprised 108 patients (tislelizumab: n = 55; chemotherapy: n = 53). Overall survival (OS) was prolonged with tislelizumab versus chemotherapy (median: 11.2 versus 6.3 months), with a hazard ratio (HR) of 0.55 [95% confidence interval (CI) 0.35-0.87]; HR was similar irrespective of programmed death-ligand 1 score [≥10%: 0.47 (95% CI 0.18-1.21); <10%: 0.55 (95% CI 0.30-1.01)]. Median progression-free survival was 2.3 versus 2.7 months with tislelizumab versus chemotherapy [HR: 0.97 (95% CI 0.64-1.47)]. Overall response rate was greater with tislelizumab (20.0%) versus chemotherapy (11.3%), with more durable response (median duration of response: 5.1 versus 2.1 months). Tislelizumab had a favorable safety profile versus chemotherapy, with fewer patients experiencing ≥grade 3 treatment-related adverse events (13.0% versus 51.0%). Those on tislelizumab experienced less deterioration in health-related quality of life, physical functioning, and/or disease- and treatment-related symptoms (i.e. fatigue, pain, and eating problems) as compared to those on chemotherapy, per the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and QLQ-OES18 scores. CONCLUSIONS: As a 2L therapy for advanced/metastatic ESCC, tislelizumab improved OS and had a favorable safety profile as compared to chemotherapy in European/North American ESCC patients in the randomized phase III RATIONALE-302 study.

Combined efficacy of low-calorie diets and aerobic training on nutritional status of obese patients with early type 2 diabetes.

OBJECTIVE: The purpose of this study was to evaluate the combined efficacy of low-calorie diets and aerobic training on the nutritional status of obese patients with early type 2 diabetes mellitus. PATIENTS AND METHODS: 120 consecutive obese patients with early type 2 diabetes were admitted to our hospital between August 2021 and December 2022. The patients enrolled were equally and randomly allocated into the control group (60 cases, given conventional diabetes diet intervention) and the study group (60 cases, given a low-calorie diet intervention combined with aerobic training). The parameters, including the nutritional status, fasting insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), blood lipid level, and quality of life, were compared between the two groups. RESULTS: Before treatment, there were no measurable differences in the levels of fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hPG), glycosylated hemoglobin (HbAlc), albumin (ALB), prealbumin (PA), and hemoglobin (Hb) between the two groups (p>0.05), whereas two months after treatment, the FBG, 2hPG, and HbAIc levels were greatly lower, and the levels of ALB, PA, and Hb were significantly higher in the study group than those in the control group (p<0.05). Before treatment, no statistically significant differences were found in FINS and HOMA-IR values between the two groups (p>0.05). Two months after treatment, however, the study group showed lower FINS and HOMA-IR values as compared to the control group, with statistically significant differences (p<0.05). Before treatment, there was no statistically significant difference in the levels of triacylglycerol, total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) between the two groups (p>0.05), while the four levels in the study group were significantly lower than those in the control group two months after treatment (p<0.05). Similarly, there were no statistically significant differences in scores of physiological, psychological, social, and therapy-related problems between the two groups before treatment (p>0.05), whereas the abovementioned scores were evidently higher in the study group than control group two months after treatment (p<0.05). CONCLUSIONS: A low-calorie diet intervention combined with aerobic training exerted good effects in terms of greatly enhancing the nutritional status among obese patients with early type 2 diabetes mellitus, which was deemed appropriate for clinical promotion and implementation.

[A comparative study on the depth of cure, hardness and microleakage applied to primary teeth of different types of bulk-fill resins].

Objective: To compare the depth of cure, surface hardness and microleakage applied to primary teeth of three types of bulk-fill resins, so as to provide reference for clinical application. Methods: Composite resin FiltekTM Z350 XT (group A) and giomer Beautifil Ⅱ (group B) were used as controls, high-viscosity bulk-fill resin FiltekTM Bulk Fill (group C), sonic-activated bulk-fill resin SonicFill 2 (group D) and flowable bulk-fill resin SDR® flow+(group E) were studied. The microstructure of each group was observed by scanning electron microscope (SEM). Specimens of each group were prepared (6 pieces per group), and the Vickers microhardness of the surface layer and different depths of each group were measured, and then the depths of cure were calculated. Twenty-five primary molars dentin were filled by resins of each group (5 teeth per group), sliced, then aged, slices of each group were developed by silver ion staining. SEM was used to observed the distribution of silver ions. Microleakage of each group were analyzed by Jonckheere-Terpstra rank sum test. Results: SEM showed that the filler particles in groups A and C were spherical and evenly distributed. The shape of the fillers in groups B, D and E were polygonal and unevenly distributed. The surface hardness of groups A, B, C, D and E were (84.97±6.30), (65.04±5.95), (57.80±1.18), (60.77±2.34), (33.32±1.83) MPa respectively. Group A had the highest hardness, while group E was the lowest, and the differences between the two groups and other groups was statistically significant (P<0.05). There were no statistically significant differences among groups B, C, and D (P>0.05). The curing depths of groups A, B, C, D and E were 2.6, 3.4, 5.8, 3.8 and 7.8 mm respectively. The largest microleakage was found in group E [2% (1/50) for grade 0, 22% (11/50) for grade 1, 30% (15/50) for grade 2, 24% (12/50) for grade 3, and 22% (11/50)for grade 4], which was statistically different from other groups (P<0.05). No statistically significant differences were found among other 3 groups (P>0.05). Conclusions: Both high-viscosity and sonic-activated bulk-fill resins have the greater depth of cure, the same hardness and microleakage as giomer, which might be an option for restoration in primary teeth.

[The value of a nomogram for predicting the outcome of intracerebral hemorrhage based on clinical characteristics and diffusion-weighted imaging of hyperintense lesions].

Objective: To investigate the value of a nomogram predicting the outcome of intracerebral hemorrhage (ICH) based on clinical characteristics and diffusion-weighted imaging (DWI) of hyperintense lesions. Methods: A case-control study. Consecutive patients, aged 30-88(59±13) years old, with ICH were recruited at the Stroke Center of Zhengzhou People's Hospital from January 2018 to August 2021. Patients were divided into a group with DWI lesions and a group without DWI lesions depending on whether there were DWI hyperintense lesions distant from the hematoma. Prognosis was evaluated at 90 days via the modified Rankin Scale (mRS). Univariate and multivariable logistic regression models were used to identify independent predictors of a poor ICH outcome (mRS score≥4), and a nomogram model was developed. The performance of the nomogram was validated via the area under the receiver operating characteristic curve (AUC) and a calibration chart. Results: Of the 303 patients included in the study, 24.8% presented with DWI lesions; 17.5% with asymptomatic DWI lesions and 7.3% with symptomatic DWI lesions. Poor outcomes were significantly more frequent in the group with DWI lesions than in the group without DWI lesions (χ2=21.32, P<0.001). In multivariable regression analysis, age [odds ratio (OR)=1.032, 95% confidence interval (CI) 1.002-1.063, P=0.035], hematoma volume (OR=1.050, 95%CI 1.011-1.090, P=0.012), hematoma location (OR=3.839, 95%CI 1.248-11.805, P=0.019), DWI lesions (OR=3.955, 95%CI 1.906-8.206, P<0.001), and baseline NIHSS scores (OR=1.102, 95%CI 1.038-1.170, P=0.001) were independent predictors of a poor outcome. In subgroup analysis patients with asymptomatic DWI lesions had a 3-fold greater risk of a poor outcome compared to those without DWI lesions (OR=3.135, 95%CI 1.382-7.112, P=0.006), and patients with symptomatic DWI lesions had a 7-fold greater risk of a poor outcome compared to those without DWI lesions (OR=7.126, 95%CI 2.279-22.277, P=0.001). A nomogram model was established based on the independent predictors for a poor outcome. The AUC of the nomogram was 0.846 (95%CI 0.795-0.898), and a calibration chart indicated good consistency between values predicted by the nomogram and actual observed values. Conclusions: DWI lesions are an independent risk factor for a poor outcome in patients with ICH-particularly symptomatic DWI lesions. A nomogram model based on clinical characteristics and DWI lesions exhibited good efficacy when predicting the outcome of ICH.

Antibody response to the COVID-19 ChAdOx1nCov-19 and BNT162b vaccines after temporary suspension of DMARD therapy in immune-mediated inflammatory disease: an extension study (RESCUE 2).

The persistence of immunogenicity in patients with immune-mediated inflammatory diseases (IMID) on disease-modifying antirheumatic therapy (DMARD) has been less well studied. This extension study evaluates the SARS-CoV2 antibody decay kinetics 6 months following two doses of ChAdO1nCov-19 (AZ) and BNT162b (Pfizer) and subsequent response following an mRNA booster. RESULTS: 175 participants were included. Six months after initial AZ vaccination, 87.5%, 85.4% and 79.2% (p=0.756) in the withhold, continue and control groups remained seropositive compared with 91.4%, 100% and 100% (p=0.226), respectively, in the Pfizer group. Both vaccine groups developed robust humoral immune responses following a booster with seroconversion rates being 100% for all three intervention categories. The mean SARS-CoV-2 antibody levels were significantly lower in the targeted synthetic DMARD (tsDMARD) group that continued therapy compared with the control (2.2 vs 4.8 U/mL, p=0.010). The mean time interval until loss of protective antibodies in the IMID group was 61 days for the AZ and 137.5 days for the Pfizer vaccine. Within each DMARD class the interval until loss of protective antibody titres in the csDMARD, bDMARD and tsDMARD groups were 68.3, 71.8 and 64.0 days in the AZ group and 185.5, 137.5 and 116.0 days in the Pfizer group, respectively. CONCLUSION: Antibody persistence was longer in the Pfizer group due to a higher peak antibody level following second vaccination with levels of protection in IMID on DMARD therapy similar to controls except in those on tsDMARDs where it was lower. A third mRNA vaccine booster can restore immunity in all groups.

[Research progress of the application of methacrylic anhydride gelatin hydrogel in wound repair].

Wound repair is a common clinical problem, which seriously affects the quality of life of patients and also brings a heavy burden to the society. Hydrogel-based multifunctional dressing has shown strong potential in the treatment of acute and chronic wounds. In addition to its good histocompatibility, cell adhesion, and biodegradability, methacrylic anhydride gelatin (GelMA) hydrogel has also attracted much attention due to its low cost, mild reaction conditions, adjustable physicochemical properties, and wide clinical applications. In this paper, the characteristics of GelMA hydrogel and its research progress in wound repair are introduced, and the future development of multifunctional GelMA hydrogel dressing for wound treatment is prospected.

[Pancreas multidisciplinary team optimizes the diagnosis and treatment of pancreas-related diseases and improves the prognosis of pancreatic cancer patients].

Objectives: To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer. Methods: The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ2 test. Results: Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months,P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%,P<0.05;32.9% vs. 21.9%,P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%,P>0.05). Conclusions: The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients' compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.

Tislelizumab versus chemotherapy as second-line treatment of advanced or metastatic esophageal squamous cell carcinoma (RATIONALE 302): impact on health-related quality of life.

BACKGROUND: RATIONALE 302 (NCT03430843) an open-label, phase III study of second-line treatment of advanced/metastatic esophageal squamous cell carcinoma (ESCC), reported that tislelizumab, relative to investigator-chosen chemotherapy (ICC), was associated with improvements in overall survival and a favorable safety profile. This study assessed the health-related quality of life (HRQoL) and ESCC-related symptoms of patients in RATIONALE 302. METHODS: Adults with advanced/metastatic ESCC whose disease progressed following prior systemic therapy were randomized 1 : 1 to receive either tislelizumab or ICC (paclitaxel, docetaxel, or irinotecan). HRQoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire Oesophageal Cancer Module 18 items (QLQ-OES18), and the EuroQoL Five-Dimensions Five-Levels (EQ-5D-5L) visual analogue scale. Mixed effect modeling for repeated measurements examined changes from baseline to weeks 12 and 18. The Kaplan-Meier method was used to examine time to deterioration. RESULTS: Overall, 512 patients were randomized to tislelizumab (n = 256) or ICC (n = 256). The tislelizumab arm maintained QLQ-C30 global health status/quality whereas the ICC arm worsened at week 12 {difference in least square (LS) mean change: 5.8 [95% confidence interval (CI): 2.0-9.5], P = 0.0028} and week 18 [difference in LS mean change: 8.1 (95% CI: 3.4-12.8), P = 0.0008]. Physical functioning (week 18) and fatigue (weeks 12 and 18) worsened less in the tislelizumab compared with the ICC arm. The tislelizumab arm improved in reflux symptoms, whereas the ICC worsened at week 12 [difference in LS mean change: -4.1 (95% CI: -7.6 to -0.6), P = 0.0229]. The visual analogue scale remained consistent in the tislelizumab arm whereas it worsened in the ICC arm. The hazard of time to deterioration was lower in tislelizumab patients compared with ICC for physical functioning and reflux. CONCLUSIONS: HRQoL, including fatigue symptoms and physical functioning, was maintained in patients with advanced or metastatic ESCC receiving tislelizumab compared with ICC-treated patients. These results provide additional support for the benefits of tislelizumab in this patient population.

Two-step aggregation of gold nanoparticles based on charge neutralization for detection of melamine by colorimetric and surface-enhanced Raman spectroscopy platform.

A colorimetric and surface-enhanced Raman scattering (SERS) signal amplification platform based on 2-step aggregation of gold nanoparticles (AuNP) was constructed for the sensitive detection of melamine. In this study, the positively charged SYBR Green I was used for the first step of aggregation of AuNP, via charge neutralization, to obtain small-sized AuNP aggregates. The positively charged SYBR Green I decreased the negative charges of the surface of AuNP, which was beneficial to the aggregation of AuNP. In addition, the melamine could aggregate AuNP by decreasing the negative charges of the surface of AuNP and self-assemble with each other on the surface of AuNP by hydrogen bonds. Therefore, the second efficient aggregation of small-sized AuNP aggregates could be achieved with melamine at low concentration, resulting in significant signal changes of color and SERS. The sensitivity of a colorimetric (0.60 mg/L) and SERS (0.089 mg/L) platform, based on 2-step aggregation of AuNP, was 15 and 2.2 times higher than that based on 1-step aggregation of AuNP for detecting melamine.

[Effect of subpressure on the bonding strength of resin to polycrystalline particulates modified zirconia ceramic].

Objective: To explore the effect of subpressure on the bonding strength of resin to polycrystalline particulates modified zirconia ceramic. Methods: One hundred and twenty pre-sintered zirconia discs were prepared and divided into the control group, the sandblasting group and the 30, 50, 70 s acid etching group (24 per group) by the random number table method. There was no additional treatment in the control group and sandblasting group before sinering. The 30, 50, and 70 s acid etching groups were immersed in HF for 30, 50, 70 s, respectively, and then they were placed into CaCl2 solution for 90 s and dipped in NaOH solution at 80 ℃ for 2 h. After sintering, the sandblasting group was subjected to sandblasting. The surface tomography and roughness were tested. According to whether subpressure was applied or not after the adhesives were applied, each group was randomly divided into two subgroups with a random number table: a subpressure subgroup and a normal pressure subgroup (12 per subgroup). Resin columns were bonded to these specimens. Shear bonding strength (SBS) test was conducted and the bonding interface, fracture surface and failure mode were analyzed. Results: The surface of control group was smooth, and its roughness was (0.24±0.11) µm. The rough surface was formed after sandblasting in the sandblasting group, and its roughness was (0.95±0.12) µm. The surface roughness of 30, 50, 70 s acid etching groups [(0.60±0.15), (1.04±0.11), (1.57±0.16) µm] increased as the HF immersion time prolonged, and the difference in surface roughness of zirconia specimens among each group was statistically significant (P<0.05). The SBS values between zirconia and resin of all the subpressure subgroups, namely: the control group, the sandblasting group, and the 30, 50, 70 s acid etching group [(13.56±1.19), (20.98±2.11), (17.37±2.44), (24.19±2.97), (21.36±2.16) MPa] were significantly stronger than those in the normal pressure subgroups, namely: the control group, sandblasting group, 30, 50, 70 s acid etching group [(10.74±0.93), (18.47±2.14), (14.81±1.54), (20.74±2.56), (17.75±2.54) MPa] (P<0.05). No obvious gaps and bubbles were observed in the bonding interfaces in subpressure subgroups. The proportion of mixed failure was significantly increased after applying subpressure (P<0.05). Conclusions: The subpressure can effectively enhance the bonding strength between the resin and polycrystalline particulates modified zirconia ceramic and improve the bonding effect.

Low-dose CT of paediatric paranasal sinus using an ultra-low tube voltage (70 kVp) combined with the flash technique.

AIM: To evaluate the radiation dose and diagnostic image quality of low-dose computed tomography (CT) of the paranasal sinus in children, with acquisition at an ultra-low tube voltage (70 kVp) combined with the Flash technique. MATERIALS AND METHODS: Eighty paediatric patients underwent CT of the paranasal sinus and were divided into two groups according to different protocols (group A: 80 kVp protocol with conventional spiral mode [n=40] and group B: 70 kVp protocol with Flash scan mode [n=40]). For each examination, the CT dose index (CTDIvol), dose-length product (DLP), and effective dose (ED) were estimated. The image noise, signal-to-noise ratio (SNR), and overall subjective diagnostic image quality were also evaluated. RESULTS: For radiation dose, the CTDIvol (mGy), DLP (mGy·cm), and ED (mSv) values of the 70 kVp protocol were significantly lower than those of the 80 kVp protocol (CTDIvol: 1.57±0.009 versus 0.39±0.004 mGy, p<0.001; DLP: 19.88±2.01 versus 6.31±0.52 mGy·cm, p<0.001; ED: 0.079±0.016 versus 0.024±0.005 mSv, p<0.001). Compared with those of the 80-kVp protocol, the image noise increased by 40.7% (p=0.113), the SNRsoft-tissue decreased by 48.9%, and the SNRbone increased by 10.1% with the 70-kVp protocol (p=0.176 and 0.227, respectively). There was no significant difference in the overall subjective image quality grades between these two groups (p=0.15). CONCLUSION: When imaging the paranasal sinus in children, an ultra-low tube voltage (70 kVp) combined with the Flash CT technique can reduce the radiation dose significantly while maintaining diagnostic image quality with clinically acceptable image noise.

Setting the new FRAX reference threshold without bone mineral density in Chinese postmenopausal women.

PURPOSE: Despite the large number of osteoporosis patients in China, the diagnosis and treatment rates remain low. The Fracture Risk Assessment Tool (FRAX) can be used to effectively evaluate fracture risk. In this study, we explored the Chinese-specific thresholds of FRAX without the T-score. METHODS: In all, 264 postmenopausal women aged > 50 years were randomly recruited from community-medical centers. All subjects completed self-reported questionnaires, BMD measurements, and spinal radiographs. The 10-year hip and major osteoporotic fracture risks were calculated by FRAX. A new threshold for both 10-year hip and major osteoporotic fracture risk was explored with receiver operating characteristic (ROC) curve analysis. RESULTS: Overall, 92 subjects were diagnosed with osteoporosis. Among them, 14 participants with T-score > - 2.5 were diagnosed with osteoporosis based on clinical fractures. ROC analysis showed the cut-off value of the 10-year hip osteoporotic fracture for detecting osteoporosis was 0.95%, while that of 10-year major osteoporotic fracture was 4.95%. The sensitivity and specificity of the 10-year hip osteoporotic fracture probability for detecting osteoporosis were 0.86 and 0.59, respectively, while the guideline-recommended threshold had a sensitivity of 0.49 and specificity of 0.83. The sensitivity and specificity of the 10-year major osteoporotic fractures with the new threshold were 0.76 and 0.69, respectively, while the recommended threshold had a sensitivity of 0 and specificity of 1. CONCLUSION: Current guideline-recommended FRAX thresholds without BMD showed low sensitivity. Therefore, 10-year osteoporotic hip fracture probability ≥ 0.95% and 10-year osteoporotic major fracture probability ≥ 4.95% are recommended as the new thresholds.

CUL4A promotes proliferation and inhibits apoptosis of colon cancer cells via regulating Hippo pathway.

OBJECTIVE: The aim of this study was to investigate the effect of cullin 4A (CUL4A) on the proliferation and apoptosis of colon cancer (CC) cells, and to elucidate its regulatory relationship with the Hippo pathway. PATIENTS AND METHODS: Paired CC tissues and adjacent normal tissues were obtained from patients. CC cells were isolated and cultured in vitro. CUL4A was interfered by small interfering ribonucleic acid (siRNA) (siR-CUL4A group) or overexpressed by overexpression vector (CUL4A-Vector group), with negative control (NC)-CUL4A or CUL4A -NC as the control group. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of CUL4A in CC tissues and cells. The proliferative ability of cells was detected by cell counting kit-8 (CCK-8) assay. Flow cytometry was applied to measure the apoptosis of cells in each group. Western blotting (WB) was conducted to determine the protein expression of CUL4A. In addition, the proliferative ability was examined in vivo through subcutaneous injection of cells into nude mice. RESULTS: QRT-PCR showed that CUL4A was highly expressed in 66.67% of CC samples (p<0.01). In vivo and in vitro proliferative ability was significantly reduced in siR-CUL4A group (p<0.01), whereas the apoptosis rate was promoted (p<0.01). However, in vivo and in vitro proliferative ability increased significantly in CUL4A-Vector group (p<0.01), while the apoptosis rate was reduced (p<0.01). The protein expressions of MST1, LATS1 and p-YAP were significantly up-regulated in siR-CUL4A group (p<0.01), while they were remarkably down-regulated in CUL4A-Vector group (p<0.05, p<0.01). CONCLUSIONS: CUL4A is highly expressed in CC and promotes the proliferation and inhibits the apoptosis of CC cells by regulating the Hippo pathway.

The expression of overexpressed PTEN enhanced IR-induced apoptosis of myocardial cells.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "The expression of overexpressed PTEN enhanced IR-induced apoptosis of myocardial cells, by Y.-B. Zhu, N. Ding, H.-L. Yi, Z.-Q. Li, published in Eur Rev Med Pharmacol Sci 2019; 23 (10): 4406-4413-DOI: 10.26355/eurrev_201905_17948-PMID: 31173315" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17948.

[Clinical and genetic characteristics of children with STXBP1 encephalopathy].

Objective: To investigate the clinical and genetic characteristics of developmental and epileptic encephalopathy (DEE) caused by syntaxin-binding protein 1 (STXBP1) gene mutation. Methods: The clinical data, gene variation and treatment outcome of 15 children with STXBP1 encephalopathy admitted to Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2014 to June 2019 were analyzed retrospectively. Results: Among 15 patients, 11 were male and 4 were female, age ranged from 2 months to 69 months. The clinical manifestations of 14 children were epilepsy and developmental delay (DD) and the remaining one showed developmental delay without seizure. The onset age of epilepsy ranged from two days to 19 months and 11 of them experienced the first attack before 1 year of age. The common seizure types were epileptic spasms and tonic seizures. Seven patients were diagnosed with Ohtahara syndrome or West syndrome. Epileptic form discharges were observed in the interictal electroencephalograms (EEG) of 11 patients, including multifocal discharges, suppression-burst and hypsarrhythmia. The brain magnetic resonance imaging of 7 children were abnormal, including myelin dysplasia, less white matter, lack of corpus callosum or hypoplasia. The follow-up time ranged from 2 months to 57 months, after the last follow-up, 3 cases were seizure free, 6 children showed partial response and the other 5 patients had no response on multitherapy. Six of 8 patients showed good responses to levetiracetam (LEV) monotherapy or in combination with other antiepileptic drugs (AEDs). Vigabatrin (VGB) was applied to 5 patients with epileptic spasms and 4 of them showed response. All patients showed different degrees of developmental delay while four of them showed autistic features. STXBP1 gene mutations were identified in all cases and there were 15 types of gene variations, including 8 missense mutations, 1 nonsense mutation, 5 frame shift mutations and 1 complex mutation. Five novel mutations were unreported before, including c.1193A>G, c.172delG, c.1769C>T, c.1038_1039delCC, c.348_351dupTGAA. Conclusions: Development delay and epilepsy are the major and independent clinical phenotypes in children with STXBP1 encephalopathy. The variation of STXBP1 gene is mainly de novo. Levetiracetam and vigabatrin may be more effective in epilepsy control than other AEDs.

[Epidemiological characteristic and current status of surgical treatment for esophageal cancer by analysis of national registry database].

Objective: To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China. Methods: A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014. Results: Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively. Conclusions: The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

Metabonomics and the Gut Microbiome Associated With Primary Response to Anti-TNF Therapy in Crohn's Disease.

BACKGROUND AND AIMS: Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn's disease. METHODS: Patients with luminal Crohn's disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces. RESULTS: Samples were collected from 76 Crohn's disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn's patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn's disease. CONCLUSIONS: This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn's disease. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Analysis of a registry database for esophageal cancer from high-volume centers in China.

Esophageal cancer has a high incidence among malignancies in China, but a comprehensive picture of the status of its surgical management in China has hitherto not been available. A nationwide database has recently been established to address this issue. METHOD: A National Database was setup through a network platform, and data was collected from 70 high-volume centers (>100 esophagectomies/per year) across China. Data was entered between January 2009 and December 2014, and was analyzed in June 2015 after a minimal follow-up of 6 months for all patients. 8181 patients with complete data who received surgery for primary esophageal cancer on the Database were included in the analysis. RESULT: In this series, there were 6052 males and 2129 females, with a mean age of 60.5 years (range: 22-90 years). The pathology in 95.5% of patients was squamous cell carcinoma. The pathological stage distribution was 1.2% in stage 0, 2.5% in Ia, 11.5% in Ib, 14.8% in IIa, 36.1% in IIb, 19.3% in IIIa, 8.3% in IIIb, 6.2% in IIIc. 1800 patients (22.0%) with locally advanced disease received preoperative neoadjuvant therapy and 3592 patients (43.9%) underwent postoperative adjuvant chemotherapy and/or radiotherapy. The esophagectomies were performed through left thoracotomy approach in 5870 cases (72.6%), through right chest approach in 2215 cases (27.4%) including right thoracotomy (21.3%) and VATS (6.1%). The 30-day postoperative mortality rate was 0.6% (43 patients), and the overall postoperative complication rate was 11.6% (951 patients). The 1-, 3-, and 5-year overall survival rates were 82.6%, 61.6%, and 52.9%, respectively. CONCLUSION: This National Registry Database from high-volume centers provides a comprehensive picture of surgical management for esophageal cancer in China for the first time. Squamous cell carcinoma predominates, but there is heterogeneity with respect to the surgical approach and perioperative oncologic management. Overall, surgical mortality and morbidity rates are low, and good survival rates have been achieved due to improvement of surgical treatment technology in recent years.