Endoscopic lithotripsy combined with drug lithotripsy vs. drug lithotripsy for the treatment of phytobezoars: analysis of 165 cases.

AIM: To analyze efficacy of endoscopic lithotripsy combined with drug lithotripsy as compared with drug lithotripsy for the treatment of phytobezoars. METHODS: We collected and evaluated case records of 165 patients with phytobezoars from 2014 to 2023. And we analyzed demographic and clinical characteristics, imaging features, endoscopic features, complications of phytobezoars, and compared efficacy between endoscopic lithotripsy combined with drug lithotripsy (Group A) and drug lithotripsy (sodium bicarbonate combined with proton pump inhibitor) (Group B). RESULTS: The median age of patients with phytobezoars was 67.84 ± 4.286 years old. Abdominal pain was the most common symptom and peptic ulcers (67.5%) were the most common complication. Bezoar-induced ulcers were more frequent in the gastric angle. The success rate of phytobezoars vanishing in Group A and Group B were similar (92.3% vs. 85.1% within 48 h, 98.7% vs. 97.7% within a week), while the average hospitalization period, average hospitalization cost, second endoscopy rate, and average endoscopic operation time were significantly lower in patients in Group B than in Group A. CONCLUSION: Drug lithotripsy is the preferred effective and safe treatment option for phytobezoars. We advise that an endoscopy should be completed after 48 h for drug lithotripsy.

Effect of structured pelvic floor muscle training on pelvic floor muscle contraction and treatment of pelvic organ prolapse in postpartum women: ultrasound and clinical evaluations.

OBJECTIVES: The purpose of this study is to examine the impact of structured pelvic floor muscle training (PFMT) on pelvic floor muscle (PFM) contraction and the treatment of pelvic organ prolapse (POP) in postpartum women. METHODS: Sixty patients who volunteered for a PFMT assessment at 6-8 weeks after delivery were included in this retrospective analysis. For 5 weeks, all patients had structured PFMT, which included supervised daily pelvic muscle contractions, biofeedback therapy, and electrical stimulation. The main outcomes were POP stage assessed by POP quantification (POP-Q), pelvic organ position and hiatus area (HA) assessed by transperineal ultrasound, PFM contraction assessed by Modified Oxford scale (MOS), surface electromyography (EMG), and sensation of PFM graded using visual analog scale (VAS). RESULTS: Structured PFMT was associated with better POP-Q scores in Aa, Ba, C, and D (p values were 0.01, 0.001, 0.017, and 0.001 separately). The bladder neck at rest and maximum Valsalva, the cervix position and HA at maximum Valsalva in transperineal ultrasound were significantly better than before (p values were 0.031, < 0.001, 0.043, and < 0.001 separately). PFM contraction assessed by MOS, EMG, and PFM VAS score were significantly improved (all p values were < 0.001). However, no significant improvement was observed in POP-Q stage. CONCLUSIONS: Structured PFMT can increase PFM function in postpartum women but cannot modify the POP-Q stage. Transperineal ultrasonography is a useful method for evaluating therapy efficacy objectively. More randomized controlled trials are needed before definitive conclusions can be drawn about the effect of structured PFMT on POP in postpartum women.

Impact of initial dialysis modality on the survival of patients with ESRD: a propensity-score-matched study.

BACKGROUND: Studies comparing the survival of hemodialysis (HD) and peritoneal dialysis (PD) patients are controversial. This study evaluated the impact of initial dialysis modality on the survival of patients with end-stage renal disease (ESRD) in a matched-pair cohort. METHODS: A retrospective cohort study was performed on ESRD patients who initiated renal replacement treatment between January 1, 2010, and December 31, 2018. Propensity score matching was applied to balance the baseline conditions, and multivariate Cox regression analysis was applied to compare mortality between HD and PD patients and evaluate correlations between mortality and various baseline characteristics. Subgroup analysis was performed with respect to diabetes status. RESULTS: There were 739 patients in our center in the Chinese National Renal Data System (CNRDS) between 2010 and 2018. Of these, 125 PD patients were matched with 125 HD patients. The 1-, 2-, and 3-year survival rates were 96.5%, 90.7%, and 82.5%, respectively, in the HD group and 99.5%, 97.8%, and 92.5%, respectively, in the PD group (log-rank P < 0.001). Among the propensity score-matched cohorts, no significant differences in Kaplan-Meier curves were observed between the two groups (log-rank P = 0.514). Age at dialysis initiation, CCI, congestive heart failure and cerebrovascular disease were risk factors in the multivariable-adjusted model. In subgroups defined by diabetes status, the Kaplan‒Meier survival curve showed that PD survival was significantly higher than that of HD (log-rank P = 0.022). CONCLUSIONS: HD and PD were not significantly different regarding the survival of patients with ESRD. PD was associated with better survival in diabetic ESRD patients.

Clinical Features, Risk Factors, and Endoscopic Treatment of Bezoars: A Retrospective Analysis from a Single Center in Northern China.

BACKGROUND The aims of this study were to summarize the clinical characteristics and risk factors for bezoars and to analyze the effectiveness and safety of the endoscopic treatment of bezoars. MATERIAL AND METHODS From January 2015 to February 2020, 75 of the 23 950 patients who underwent gastroscopic examination in our medical center were diagnosed with bezoars. Clinical and treatment information for these patients was collected retrospectively and analyzed. RESULTS The detection rate of bezoars was 0.31%. Risk factors included the time of year (autumn and winter seasons), alcohol consumption, hypertension, diabetes, and residing in the Mentougou district, which is rich in hawthorn and persimmon. Abdominal pain (90.7%) and bloating (80.0%) were common clinical symptoms of bezoars, while gastric mucosa erosion (90.7%) and gastric ulcers (60%) were common manifestations on endoscopic examination. Six patients with bezoars were successfully discharged after drug treatment. The success rate for bezoars treated by gastroscopic lithotripsy was 94.2% (65/69 patients). The factors affecting the therapeutic effect of bezoars include patient age (P=0.025) and bezoar size (P=0.042). Patients with bezoars larger than 9 cm were significantly more likely to have intestinal obstructions than were patients with bezoars smaller than 9 cm (P<0.001). CONCLUSIONS Bezoars mainly occur in elderly patients with diseases such as gastrointestinal dyspraxia and diabetes, and are most common in hawthorn and persimmon producing areas. Endoscopic treatment is safe and effective for bezoars in general, but intestinal obstruction should be considered for bezoars larger than 9 cm.

Matrine attenuates high-fat diet-induced in vivo and ox-LDL-induced in vitro vascular injury by regulating the PKCα/eNOS and PI3K/Akt/eNOS pathways.

Lipid metabolism disorders lead to vascular endothelial injury. Matrine is an alkaloid that has been used to improve obesity and diabetes and for the treatment of hepatitis B. However, its effect on lipid metabolism disorders and vascular injury is unclear. Here, we investigated the effect of matrine on high-fat diet fed mice and oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs). Computational virtual docking analyses, phosphoinositide 3-kinase (PI3K) and protein kinase C-α (PKCα) inhibitors were used to localize matrine in vascular injuries. The results showed that matrine-treated mice were more resistant to abnormal lipid metabolism and inflammation than vehicle-treated mice and exhibited significantly alleviated ox-LDL-stimulated dysfunction of HUVECs, restored diminished nitric oxide release, decreased reactive oxygen species generation and increased expression phosphorylation of AKT-Ser473 and endothelial nitric oxide synthase (eNOS)-Ser1177. Matrine not only up-regulates eNOS-Ser1177 but also down-regulates eNOS-Thr495, a PKCα-controlled negative regulator of eNOS. Using computational virtual docking analyses and biochemical assays, matrine was also shown to influence eNOS/NO via PKCα inhibition. Moreover, the protective effects of matrine were significantly abolished by the simultaneous application of PKCα and the PI3K inhibitor. Matrine may thus be potentially employed as a novel therapeutic strategy against high-fat diet-induced vascular injury.

Multicenter-Based Population Pharmacokinetic Analysis of Ciclosporin in Hematopoietic Stem Cell Transplantation Patients.

PURPOSE: To explore the contribution of physiological characteristics to variability in ciclosporin pharmacokinetics in hematopoietic stem cell transplantation patients. METHODS: Clinical data from 563 patients were collected from centers in three regions. Ciclosporin concentrations were measured using immunoassays. The patients' demographics, hematological and biological indicators, coadministered drugs, region, and disease diagnosis were recorded from medical records. Data analysis was performed using NONMEM based on a one-compartment model to describe the pharmacokinetics of ciclosporin. The reliability and stability of the final model were evaluated using bootstrap resampling, goodness-of-fit plots, and prediction-corrected visual predictive checks. RESULTS: The population estimate of the clearance (CL) was 30.4 L/h, the volume of distribution (V) was 874.0 L and the bioavailability (F) was 81.1%. The between-subject variability in these parameters was 26.3, 68.0, and 110.8%, respectively. Coadministration of fluconazole, itraconazole, or voriconazole decreased CL by 17.6%, 28.4%, and 29.2%, respectively. Females' CL increased by approximately 12.0%. In addition, CL and V decreased with hematocrit, total protein, and uric acid increase, and CL also decreased with age and aspartate aminotransferase increase. However, CL increased with creatinine clearance increase. CONCLUSIONS: A multicenter-based population pharmacokinetic model of ciclosporin was established. The pharmacokinetics of ciclosporin exhibited discrepancies among different regions.

Effect of 48-week pegylated interferon α-2a or nucleos(t)ide analogue therapy on renal function in Chinese patients with chronic hepatitis B.

BACKGROUND: Controversy remains as to whether antiviral agents contribute to renal dysfunction in patients with chronic hepatitis B virus (HBV) infection. Thus, the aim of study was to analyze the changes in renal function of chronic hepatitis B (CHB) patients in response to anti-HBV therapy and the association with treatments. METHOD: We performed a retrospective observational cohort study to investigate factors associated with renal function in 249 Chinese CHB patients who were treated with pegylated interferon α-2a (PEG-IFN-α-2a) or nucleos(t)ide analogues for 48 weeks. Changes of estimated glomerular filtration rate (eGFR), which was computed with both the Chronic Kidney Disease Epidemiology Collaboration and the Modification of Diet in Renal Disease formulas, were tested by repeated measures One-way analysis of variance within groups. A linear mixed effects model for repeated measures was also used to evaluate the association between baseline information and eGFR changes over time in all enrolled patients. The model considered the baseline age, sex, HBV DNA, aminotransferase, blood urea nitrogen, treatment group, time, and group-by-time interaction as fixed effects and incorporated random effects for individual subjects. RESULTS: The eGFR increased in patients given PEG-IFN-α-2a, decreased in patients given adefovir, but remained stable in patients given entecavir. Age and blood urea nitrogen were significant negative predictive factors for eGFR changes. CONCLUSION: In real-life study, PEG-IFN-α-2a therapy in CHB patients increased eGFR, thus may associate with renoprotective effects when compared with adefovir or entecavir therapies.

Prediction of cervical lymph node metastasis in patients with papillary thyroid cancer using combined conventional ultrasound, strain elastography, and acoustic radiation force impulse (ARFI) elastography.

OBJECTIVES: To investigate the value of combined conventional ultrasound (US), strain elastography (SE) and acoustic radiation force impulse (ARFI) elastography for prediction of cervical lymph node metastasis (CLNM) in papillary thyroid cancer (PTC). METHODS: A consecutive series of 203 patients with 222 PTCs were preoperatively evaluated by US, SE, and ARFI including virtual touch tissue imaging (VTI) and virtual touch tissue quantification (VTQ). A multivariate analysis was performed to predict CLNM by 22 independent variables. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance. RESULTS: Multivariate analysis demonstrated that VTI area ratio (VAR) > 1 was the best predictor for CLNM, followed by abnormal cervical lymph node (ACLN), capsule contact, microcalcification, capsule involvement, and multiple nodules (all P < 0.05). ROC analyses of these characteristics showed the areas under the curve (Az), sensitivity, and specificity were 0.600-0.630, 47.7 %-93.2 %, and 26.9 %-78.4 % for US, respectively; and they were 0.784, 83.0 %, and 73.9 %, respectively, for VAR > 1. As combination of US characteristics with and without VAR, the Az, sensitivity, and specificity were 0.803 and 0.556, 83.0 % and 100.0 %, and 77.6 % and 11.2 %, respectively (P < 0.001). CONCLUSIONS: ARFI elastography shows superior performance over conventional US, particularly when combined with US, in predicting CLNM in PTC patients. KEY POINTS: • Conventional ultrasound is useful in predicting cervical lymph node metastasis preoperatively. • Virtual touch tissue imaging area ratio is the strongest predicting factor. • Predictive performance is markedly improved by combining ultrasound characteristics with VAR. • Acoustic radiation force impulse elastography may be a promising complementary tool.

Virtual Touch Tissue Imaging for Differential Diagnosis of Thyroid Nodules: Additional Value of the Area Ratio.

OBJECTIVES: To evaluate the additional value of the area ratio on Virtual Touch tissue imaging (VTI; Siemens Medical Solutions, Mountain View, CA) for diagnosis of thyroid nodules referred to surgery. METHODS: From April 2013 to February 2014, 205 consecutive patients with 225 histologically proven thyroid nodules were enrolled in this retrospective study. Virtual Touch tissue imaging and area ratio measurements were performed for each nodule. The area ratio was defined as the area of the nodule on VTI divided by the area on B-mode sonography. Nodule stiffness on VTI was graded from I (soft) to VI (hard). Receiver operating characteristic curve analyses of VTI, area ratio, and the combination of VTI and area ratio were performed. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and Youden index were also evaluated. RESULTS: By receiver operating characteristic curve analyses, the cutoff values were VTI grade IV and area ratio of 1.09, respectively. Nodules with VTI grade IV or higher or area ratio of 1.09 or higher were more likely to be malignant. The sensitivity, specificity, accuracy, PPV, NPV, and Youden index were 78.6%, 92.3%, 88.0%, 82.1%, 90.5%, and 0.709 for VTI and 81.4%, 87.1%, 85.3%, 74.0%, 91.2%, and 0.685 for area ratio (all P > .05). However, when using the criterion of VTI grade IV or higher and area ratio of 1.09 or higher as a combination, the sensitivity, specificity, accuracy, PPV, NPV, and Youden index increased to 94.3%, 97.4%, 96.4%, 94.3%, 97.4%, and 0.917 (all P< .05 compared to VTI or area ratio alone, except for specificity between VTI and the combination). CONCLUSIONS: The diagnostic performance of VTI grading and the area ratio for differentiation between benign and malignant thyroid nodules is equivalent. The performance is further improved with a combination of VTI grading and area ratio analysis.

Tracing the nitrogen metabolites of glycine using (15)N-glycine and mass spectrometry.

RATIONALE: Glycine is the smallest amino acid used in protein synthesis, but it is also a very important precursor for the biosynthesis of other nitrogen-containing metabolites, such as purine nucleosides and nucleotides for synthesis of RNA, DNA etc. Abnormalities in glycine metabolism therefore cause diseases such as cancer. A quick and unambiguous method to trace the metabolites arising from glycine is required for targeting defect points within metabolic networks. METHODS: This paper describes a method for using (15)N-glycine to culture A549 cancer cells for use with high-resolution mass spectrometry (HRMS) and tandem mass spectrometry (HRMS(2)) that can detect the (M+1)/M pair peaks appearing in the cell metabolites. The 1 Da difference in the pair peaks can be used to point out and identify the nitrogen metabolites of glycine. RESULTS: Thirteen nitrogen-containing metabolites derived from glycine were confirmed. Among them were metabolites containing purine, such as adenine, adenosine, AMP, ADP, ATP, S-adenosylmethionine and γ-glutathione; these were the most sensitive to the (15)N-glycine-enrichment technique. Therefore, they are promising biomarkers for monitoring the glycine metabolism network. CONCLUSIONS: The method developed here could be applied to investigations of metabolism of other amino acids, and for drug discovery studies targeting the enzymes related to amino acid metabolism.

Conventional US, US elasticity imaging, and acoustic radiation force impulse imaging for prediction of malignancy in thyroid nodules.

PURPOSE: To evaluate conventional ultrasonography (US), US elasticity imaging (EI), and acoustic radiation force impulse (ARFI) imaging in thyroid nodule malignancy prediction. MATERIALS AND METHODS: This prospective study was institutional review board approved; informed consent was obtained. Study included 375 patients (mean age, 51 years; range, 18-75 years) with 441 pathologically proven thyroid nodules. In 281 women (mean age, 50 years; range, 18-75 years) and 94 men (mean age, 53 years; range, 18-74 years), conventional US, EI, Virtual Touch tissue imaging (VTi; Siemens, Mountain View, Calif), and Virtual Touch tissue quantification (VTq; Siemens) of ARFI imaging were performed for each nodule. Multivariate logistic regression analysis was performed to assess 17 independent variables for malignancy prediction. Diagnostic performance was evaluated with receiver operating characteristic (ROC) curve analysis. RESULTS: There were 325 benign and 116 malignant nodules. Marked hypoechogenicity (odds ratio [OR]: 83.88; 95% confidence interval [CI]: 17.81, 394.99) was the strongest independent predictor for thyroid malignancy, followed by shape taller than wide (OR: 8.69; 95% CI: 2.87, 26.31), VTi (OR: 6.54; 95% CI: 3.61, 11.88), moderate hypoechogenicity (OR: 3.98; 95% CI: 1.13, 14.05), poorly defined margin (OR: 3.27; 95% CI: 1.22, 8.77), female sex (OR: 2.55; 95% CI: 1.33, 4.91), coarse background of surrounding thyroid tissue (OR: 2.01; 95% CI: 1.12, 3.62), and VTq (OR: 1.78; 95% CI: 1.28, 2.47) (all P < .05). EI was not significantly associated with thyroid malignancy (P = .855). Area under the ROC curve (Az) for VTq and VTi was higher than that with other significant independent variables. Az, sensitivity, and specificity were 0.91 (95% CI: 0.87, 0.94) and 0.86 (95% CI: 0.82, 0.90), 80% and 71.6%, and 93.8% and 83.4%, respectively, for VTi and VTq. VTq of at least 2.87 m/sec and VTi of at least grade IV were the best cutoff values for malignant thyroid nodules. CONCLUSION: ARFI imaging is promising for malignant thyroid nodule prediction, with higher diagnostic performance than conventional US or EI. ARFI can be used to supplement conventional US to diagnose thyroid nodules in patients referred for surgery.

Virtual touch tissue imaging on acoustic radiation force impulse elastography: a new technique for differential diagnosis between benign and malignant thyroid nodules.

Objectives- Acoustic radiation force impulse elastography is a newly developed ultrasound elasticity imaging technique that included both Virtual Touch tissue quantification and Virtual Touch tissue imaging (VTI; Siemens Medical Solutions, Mountain View, CA). This study aimed to evaluate the usefulness of VTI in differentiating malignant from benign thyroid nodules. Methods- This study included 192 consecutive patients with thyroid nodules (n = 219) who underwent surgery for compressive symptoms or suspicion of malignancy. Tissue stiffness on VTI elastography was scored from 1 (soft) to 6 (hard). The VTI scores between malignant and benign thyroid nodules were compared. The intraobserver and interobserver agreement for VTI elastography was also assessed. Results- On VTI elastography: score 1 was found in 84 nodules (all benign); score 2 in 37 nodules (3 papillary carcinomas and 34 benign nodules); score 3 in 25 nodules (1 medullary carcinoma, 6 papillary carcinomas, and 18 benign nodules); score 4 in 53 nodules (50 papillary carcinomas and 3 benign nodules); score 5 in 17 nodules (14 papillary carcinomas and 3 benign nodules); and score 6 in 3 nodules (all papillary carcinomas). A VTI elasticity score of 4 or greater was highly predictive of malignancy (P< .01), and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 87.0% (67 of 77), 95.8% (136 of 142), 91.8% (67 of 73), 93.1% (136 of 146), and 92.7% (203 of 219), respectively. The κ values were 0.69 for intraobserver agreement and 0.85 for interobserver agreement. Conclusions- Virtual Touch tissue elasticity imaging has great potential as an adjunctive tool combined with conventional sonography for differential diagnosis between benign and malignant thyroid nodules.

A bioequivalence study of trifluridine/tipiracil tablets in Chinese metastatic colorectal cancer patients under fed conditions.

PURPOSE: Colorectal cancer (CRC) is the second most common cause of cancer death worldwide. Trifluridine (FTD) remained at higher concentrations longer when administered along with tipiracil (TPI) compared with FTD alone. Lonsurf® is a combination formulation consisting of FTD and TPI. This study aimed to investigate the bioequivalence of FTD/TPI formulations in Chinese metastatic colorectal cancer (mCRC) patients. METHODS: In this phase I, randomized, open-label, single-dose, two-sequence, four-cycle crossover study in mCRC patients, the bioequivalence of 60 mg (20 mg tablet, 3 tablets) of the test formulation and the reference formulation (Lonsurf®) was evaluated. Due to its high variability, the method of reference-scaled average bioequivalence (RSABE) was used to investigate the bioequivalence of the test and reference formulations. RESULTS: Thirty-two patients were enrolled. 78.1% of the subjects were male, and the mean (standard deviation) age was 53.9 (SD = ± 9.0) years old. The time to reach the maximum plasma concentration (Tmax) was almost 2.0 h post-dose. The geometric least-squares mean ratios (GMRs) (test/reference) of Cmax and AUC0-t for FTD were 95.3% and 102.9%, respectively, with 90% confidence intervals (CIs) for the natural log-transformed ratios of Cmax and AUC0-t of 90.0-100.9% and 99.9-105.9%, while the GMRs of Cmax and AUC0-t for TPI were 95.7% and 100.7%, respectively, with 90% CIs of 90.5-101.2% and 97.0-104.7%. In addition, the GMRs of Cmax and AUC0-t for FTD's major metabolite, trifluorothymine (FTY), were 94.8 (90% CI 90.3-99.5%) and 99.33 (90% CI 96.9-101.9%), respectively. These were in accord with the FDA bioequivalence definition interval of 80-125%. CONCLUSION: The test and reference FTD/TPI formulations were bioequivalent in Chinese mCRC patients under fed conditions.

Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

[Predicative value of expression of TrkB and TRIM29 in biopsy tissues from preoperative gastroscopy in lymph node metastasis of gastric cancer].

OBJECTIVE: To analyze the expressions of TrkB and TRIM29 in biopsy tissues from preoperative gastroscopy in patients with gastric cancer and investigate the relationship between their expression and rate of lymph node metastasis. METHODS: Through immunohistochemistry, the authors analyzed the expression status of TRIM29 and TrkB in biopsy tissues from preoperative gastroscopy in 67 patients with a diagnosis of gastric cancer undergoing radical operations during 2005 - 2009 at Peking University Third Hospital. There were 39 males and 28 females. Then the relationship was explored between the expression of both proteins and lymph node metastasis and other clinical pathological factors. Image pro Plus 6.0 software was used for image analysis. The data underwent a logarithmic process and were analyzed through SPSS 17.0 statistical software. RESULTS: The expression of TrkB in lymph node metastasis (n = 42) was higher than that in without lymph node metastasis (n = 25) (lgA 4.79 ± 0.42 vs 3.98 ± 0.71, t = -5.873, P = 0.003), while the expression of TRIM29 with lymph node metastasis (n = 36) was also higher than that in without lymph node metastasis (n = 24) (5.21 ± 0.27 vs 5.02 ± 0.37, t = -2.257, P = 0.040). Logistic regression analysis showed that the TrkB expression was an independent predictor for lymph node metastasis. A discriminant was set based on the result (discriminant value = 1.705 × TrkB lgA+ 1.803 × TRIM29 lgA-16.880, cutoff value = 0). This discriminant achieved a prediction accuracy of 80.0% (48/60), a positive likelihood ratio 3.332 and a negative likelihood ratio 0.223. Patients with a high expression of TrkB showed a worse survival rate than those with a low TrkB expression [36.0% (9/25) vs 66.7% (16/24), P = 0.047). Patients with a high TRIM 29 expression showed a worse survival rate than those with a low TRIM29 expression [38.1% (8/21) vs 66.7% (14/21), P = 0.044]. CONCLUSION: The expressions of TrkB and TRIM29 are correlated with lymph node metastasis in gastric cancer, and discriminant based on the expressions of TrkB and TRIM29 had important values for preoperative prediction of lymph node metastasis in gastric cancer.

Lonicerae japonicae flos ameliorates radiotherapy-induced mesenteric artery endothelial dysfunction through GTPCH1/BH4/eNOS pathway.

BACKGROUND: As a traditional Chinese medicine, Lonicerae japonicae flos (LJF) and its main component chlorogenic acid (CGA) have anti-oxidant, anti-bacterial and anti-tumor effects. However, there is no research on the potential of LJF for vascular protection in radiotherapy. PURPOSE: To elucidate the potential and possible mechanisms of the LJF extract and CGA in alleviating endothelial dysfunction caused by abdominal radiotherapy. METHODS: LJF was extracted with water and the CGA content was analyzed by HPLC. Male Sprague-Dawley rats received abdominal radiotherapy for 21 days. Seven days after irradiation, Laser Doppler and ex vivo vascular tension experiments were performed. Nitric oxide (NO), superoxide anion levels and tetrahydrobiopterin (BH4) content were detected. Western blot, flow cytometry and molecular docking were used. RESULTS: In the radiotherapy group, the mesenteric arterial blood perfusion, NO, and superoxide anion levels were significantly reduced; rats treated with the LJF extract or CGA showed a certain extent of recovery of these indicators. Vascular tension experiments showed that CGA and the LJF extract improved the vasodilation of mesenteric arteries. Cell experiments demonstrated that CGA increased the NO content and reduce superoxide anion production and cell apoptosis. The expression levels of GTPCH1/BH4/eNOS signaling pathway were significantly increased due to the use of the LJF extract or CGA in vivo and in vitro. CONCLUSIONS: Our study demonstrated for the first time that LJF and its main component, CGA could prevent abdominal radiotherapy-induced vascular endothelial dysfunction via GTPCH1/BH4/eNOS pathway. LJF could be a potential therapeutic herbal agent.

[A comparison of proteomic analysis of Helicobacter pylori in patients with gastritis and gastric cancer between areas of high and low incidence of gastric cancer].

OBJECTIVE: To identify the differentially expressed proteins of Helicobacter pylori (Hp) in patients with gastritis and gastric cancer from areas of high and low incidence of gastric cancer by 2-dimensional electrophoresis (2-DE), and to discuss the role of bacterial factor in pathogenesis. METHODS: Hp in the endoscopic biopsy specimens of gastric mucosa of patients with gastritis and gastric cancer from areas of high (Xining) and low (Beijing) incidence of gastric cancer, were separated, cultured and saved at -80°C. The bacteria were recovered. Then the whole-cell protein of the Hp were extracted and characterized by 2-DE. The different protein spots were analyzed by PDQuest analysis software and identified by electrospray ionization quadruple time-of-flight mass spectrometry (ESI-Q-TOF-MS), and searched by the Mascot database. RESULTS: Nine differentially expressed proteins were identified, and four protein spots were over expressed in the protein maps from gastric cancer in both areas, which were: Urease subunit alpha, chaperone protein dnaK, superoxide dismutase, DNA-directed RNA polymerase subunit alpha; two protein spots were over expressed in the protein maps from gastritis in both areas, which were: Probablethiol peroxidase, nucleoside diphosphate kinase; 60×10(3) chaperonin, and inorganic pyrophosphatase were over expressed only in the protein map from gastric cancer in Xining; S-ribosyl homocysteinelyase was over expressed only in the protein map from gastric cancer in Beijing. CONCLUSION: There are differences between proteomic analyses of Hp in patients with gastritis and gastric cancer in areas of high and low incidents of gastric cancer, but 2/3 of the protein spots over expressed in the areas are consistent. The protein spots over expressed from gastric cancer in the area with high incidence of gastric cancer are more than in the area with low incidence of gastric cancer. For the Hp extracted from patients with gastric cancer, the mechanism of gastric cancer may be similar, but the role of the Hp from the area with high incidence of gastric cancer may be stronger.

Transperineal pelvic floor ultrasound for analyzing the outcomes of pelvic floor surgery for the treatment of anterior compartment prolapse: A comparative study of transvaginal mesh and native-tissue repair.

OBJECTIVE: To compare the outcomes of transvaginal mesh (TVM) and native-tissue repair (NTR) for the repair of anterior compartment prolapse. METHODS: This retrospective study involved 90 patients with anterior compartment prolapse who underwent pelvic organ prolapse surgery between January 2018 and October 2020. A TVM was used to treat 53 patients and 37 underwent NTR. All patients underwent a standardized interview, clinical examination, and four-dimensional pelvic floor ultrasound (PFUS) before and after the surgery. The primary outcome was anatomic recurrence evaluated by ultrasonic parameters. The secondary outcomes were subjective recurrence and complications. RESULTS: Subjective recurrence was 9.43% (5/53) for TVM and 16.22% (6/37) for NTR (P = .522). Significant recurrence of prolapse on ultrasound occurred in five patients (9.43%) after TVM and 12 (32.43%) after NTR; there was a significant difference between the TVM and NTR groups (P = .006). In the TVM group, the mesh was visible on ultrasound in each patient. The mesh exposure rate was 1.89% (1/53). The postoperative hiatal area reduction in the TVM group, compared with the NTR group, was statistically significant (5.55 ± 4.71 cm2 vs 3.09 ± 5.61 cm2 , P = .027). The incidence of de novo stress urinary incontinence was higher in the TVM group (20.75% vs 2.70%, P = .03). After surgery, there were significant differences between the two groups based on bladder descent (12.02 ± 8.64 mm vs 22.41 ± 13.95 mm, P = .000) and urethral rotation angle (25.26 ± 13.92° vs 40.27 ± 23.72°, P = .001). CONCLUSION: PFUS is effective for evaluating postoperative outcomes. TVM facilitates a better anatomic cure than NTR for anterior compartment prolapse.

Identification of a new orthonairovirus associated with human febrile illness in China.

The genus Orthonairovirus, which is part of the family Nairoviridae, includes the important tick-transmitted pathogens Crimean-Congo hemorrhagic fever virus and Nairobi sheep disease virus, as well as many other poorly characterized viruses found in ticks, birds and mammals1,2. In this study, we identified a new orthonairovirus, Songling virus (SGLV), from patients who reported being bitten by ticks in Heilongjiang Province in northeastern China. SGLV shared similar genomic and morphological features with orthonairoviruses and phylogenetically formed a unique clade in Tamdy orthonairovirus of the Nairoviridae family. The isolated SGLV induced cytopathic effects in human hepatoma cells in vitro. SGLV infection was confirmed in 42 hospitalized patients analyzed between 2017 and 2018, with the main clinical manifestations being headache, fever, depression, fatigue and dizziness. More than two-thirds (69%) of patients generated virus-specific antibody responses in the acute phase. Taken together, these results suggest that this newly discovered orthonairovirus is associated with human febrile illness in China.

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.