[Clinical management of thrombocytopenia in cirrhosis].

Thrombocytopenia is one of the common complications of cirrhotic patients, which can induce an increasing bleeding risk and closely correlate with bleeding following invasive procedures. Consequently, how to respond to thrombocytopenia is crucial for improving the prognosis of patients with cirrhosis. This article reviews the main mechanisms of cirrhosis concurrent with thrombocytopenia, as well as the corresponding clinical management strategies.

[Safety of umeclidinium/vilanterol in Chinese patients in a real-world setting: a prospective, multicenter, single-arm, observational study].

Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.

Comparative analysis of molecular fingerprints in prediction of drug combination effects.

Application of machine and deep learning methods in drug discovery and cancer research has gained a considerable amount of attention in the past years. As the field grows, it becomes crucial to systematically evaluate the performance of novel computational solutions in relation to established techniques. To this end, we compare rule-based and data-driven molecular representations in prediction of drug combination sensitivity and drug synergy scores using standardized results of 14 high-throughput screening studies, comprising 64 200 unique combinations of 4153 molecules tested in 112 cancer cell lines. We evaluate the clustering performance of molecular representations and quantify their similarity by adapting the Centered Kernel Alignment metric. Our work demonstrates that to identify an optimal molecular representation type, it is necessary to supplement quantitative benchmark results with qualitative considerations, such as model interpretability and robustness, which may vary between and throughout preclinical drug development projects.

Deficient chaperone-mediated autophagy in macrophage aggravates inflammation of nonalcoholic steatohepatitis by targeting Nup85.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH), a more severe subtype of nonalcoholic fatty liver disease, can cause cirrhosis and hepatocellular carcinoma. Macrophages play critical roles in initiating and maintaining NASH-induced liver inflammation and fibrosis. However, the underlying molecular mechanism of macrophage chaperone-mediated autophagy (CMA) in NASH remains unclear. We aimed to investigate the effects of macrophage-specific CMA on liver inflammation and identify a potential therapeutic target for NASH treatment. METHODS: The CMA function of liver macrophages was detected using Western blot, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and flow cytometry. By constructing myeloid-specific CMA deficiency mice, we evaluated the effects of deficient CMA of macrophages on monocyte recruitment, liver injury, steatosis and fibrosis in NASH mice. A label-free mass spectrometry was utilized to screen the substrates of CMA in macrophages and their mutual interactions. The association between CMA and its substrate was further examined by immunoprecipitation, Western blot and RT-qPCR. RESULTS: A typical hallmark in murine NASH models was impaired CMA function in hepatic macrophages. Monocyte-derived macrophages (MDM) were the dominant macrophage population in NASH, and CMA function was impaired in MDM. CMA dysfunction aggravated liver-targeted recruitment of monocyte and promoted steatosis and fibrosis. Mechanistically, Nup85 functions as a substrate for CMA and its degradation was inhibited in CMA-deficient macrophages. Inhibition of Nup85 attenuated the steatosis and monocyte recruitment caused by CMA deficiency in NASH mice. CONCLUSIONS: We proposed that the impaired CMA-induced Nup85 degradation aggravated monocyte recruitment, promoting liver inflammation and disease progression of NASH.

Differentiating between normal and fetal growth restriction-complicated placentas: is T2∗ imaging imaging more accurate than conventional diffusion-weighted imaging?

AIM: To compare the performance of T2∗ imaging and apparent diffusion coefficient (ADC) in differentiating normal placentas from those complicated by fetal growth restriction (FGR). MATERIALS AND METHODS: This prospective study included 28 control and 30 FGR placentas. Gradient-echo magnetic resonance imaging (MRI) at 16 different echo times and diffusion-weighted imaging (b-value of 0 and 800 s/mm2) were performed on all pregnant women using a 3 T MRI system. RESULTS: Both T2∗ imaging Z-score and ADC were significantly lower in the FGR placentas (ADC, (1.69 ± 0.19) × 10-3 versus (1.42 ± 0.28) × 10-3 mm2/s, p<0.001; T2∗ imaging Z-score, -0.004 ± 0.95 versus -2.441 ± 1.48, p<0.001). The area under the curve for T2∗ imaging Z-score and ADC was 0.917 (95% confidence interval [CI] = 0.842-0.991) and 0.788 (95% CI = 0.655-0.887), respectively. The performance of T2∗ imaging in differentiating FGR placentas was significantly better than that of ADC (Z = 2.043, p=0.041). CONCLUSION: Placental T2∗ imaging was found to be more reliable than ADC in differentiating between normal and FGR placentas.

[The effect of chronic endometritis on the clinical outcomes of patients with failure of first embryo transfer].

Objective: To investigate the effect of chronic endometritis (CE) on the clinical outcomes of patients with failure of first embryo transfer. Methods: A total of 5 605 cycles of frozen-thawed single blastocyst transfer in the reproductive center of the Third Affiliated Hospital of Zhengzhou University from January 2017 to June 2021 were retrospectively collected. After the failure of first embryo transfer, all patients underwent hysteroscopy, and when necessary, endometrial pathology and immunohistochemistry were combined to diagnose CE. Patients were divided into two groups: non-CE group (5 033 cycles) and CE treatment group (572 cycles). The main outcome was live birth rate and the secondary outcomes included clinical pregnancy rate and early abortion rate. The quantitative data were represented by Median (Q1, Q3). The rank sum test was used for comparison between groups. The factors related to live birth rate were analyzed by binary logistic regression model. Results: The incidence of CE was 10.21% (572 cycles) in patients with the failure of first embryo transfer. The maternal age in the non-CE group was 31.0 (29.0, 34.0) years old, and that in the CE treatment group was 31.0 (29.0, 34.0) years old (P<0.001). There was a statistically significant difference in endometrial preparation between the two groups (P=0.010). The endometrial thickness in the CE group was 9.0 (8.2, 10.3) mm on progesterone transformation day, which was higher than that of [9.5 (8.6, 11.0) mm] in the non-CE group (P<0.001). There was no significant difference in clinical pregnancy rate (60.3% (3 035 cycles) vs 63.1% (361 cycles), P=0.193), early abortion rate (17.1% (520 cycles) vs 20.5% (74 cycles), P=0.112) and live birth rate (49.2% (2 477 cycles) vs 49.3% (282 cycles), P=0.969) between the non-CE group and the CE treatment group. The maternal age, endometrial thickness on progesterone transformation day and blastocyst grade were related factors of the live birth rate, and the OR(95%CI) were 0.94 (0.93-0.96), 1.10 (1.06-1.14) and 2.07 (1.84-2.32)), respectively (all P<0.001). Compared with the non-CE group, the CE treatment group did not affect the live birth rate after transplantation, the aOR (95%CI) was 0.99 (0.82-1.18), P=0.882. Conclusions: For patients who underwent the failure of first embryo transfer, hysteroscopy is recommended before single frozen blastocyst transfer, and if necessary, combined with immunohistochemical screening for CE. After standardized treatment, CE patients could obtain similar clinical pregnancy rate, early miscarriage rate and live birth rate as non-CE patients.

[The effect of unexpected follicular development in artificial cycles on the clinical outcomes in frozen thawed embryo transfer based on propensity score matching].

Objective: To study the effect of unexpected follicular development in artificial cycles on the clinical outcomes in frozen thawed embryo transfer based on propensity score matching(PSM). Methods: The retrospective cohort study analyzed the clinical data of 7 064 cycles (5 716 patients) of artificial cycle frozen-thawed embryo transfer (AC-FET) in the Reproduction Center of the Third Affiliated Hospital of Zhengzhou University from January 1, 2016 to December 31, 2020. The clinical data were divided into three groups according to the degree of follicular development in AC-FET: no follicular growth group (group A, 6 349 cycles), small follicular growth group (group B, 248 cycles), and large follicular growth group (group C, 467 cycles). Differences in clinical outcomes between the small follicle growth group (Group B) and the large follicle growth group (Group C) were compared with the no follicle growth group (Group A) after PSM and logistic regression to adjust for confounding factors at baseline. A binary logistic regression model was used to analyze the factors related to the unanticipated follicular development in AC-FET. Results: Age [M(Q1,Q3)] was [31.0 (28.0, 36.0)] years in Group A, [34.5 (30.0, 40.0)] years in Group B, and [36.0 (31.0, 41.0)] years in Group C. After adjusting for confounders, the differences between Groups A and B in clinical pregnancy rate (P=0.169), live birth rate (P=0.318), early abortion rate (P=0.470), and miscarriage rate (P=0.783) were not statistically significant. The differences in clinical pregnancy rate (P=0.743), live birth rate (P=0.486) and miscarriage rate (P=0.080) between Groups A and C were not statistically significant, while early miscarriage rate (P=0.034) differences were statistically significant. The age, BMI, basal AFC, AMH and starting dose of estrogen were correlates of the emergence of non-expected small follicles in Groups B and A. The adjusted OR (AOR) values (95%CI) were 1.03 (1.01-1.06), 0.93 (0.90-0.98), 0.97 (0.95-0.99), 0.96 (0.95-0.97), and 0.59 (0.45-0.77), all P<0.05. Age, basal AFC, AMH and starting dose of estrogen were the associated factors of the appearance of non-expected large follicles in Groups C and A. The AOR values (95%CI) were 1.03 (1.01-1.05), 0.93 (0.91-0.95), 0.96 (0.95-0.97), and 0.52 (0.42-0.64), all P<0.05. Conclusions: In AC-FET, the clinical outcome of small follicular growth is similar to that of unfollicular growth; Compared with the growth without follicles, the growth and development of large follicles can reduce the early abortion rate; Patients with older age, less AFC, lower AMH, and lower initial dose of estrogen could be more likely to have unanticipated follicular development during endometrial preparation.

[Efficacy and influencing factors of immunotherapy combined with chemotherapy and bevacizumab in patients with non-small cell lung cancer after epidermal growth factor receptor tyrosine kinase inhibitors treatment failure].

Objective: To investigate the efficacy and influencing factors of immunotherapy combined with chemotherapy and bevacizumab in patients with non-small cell lung cancer (NSCLC) who failed epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. Methods: A retrospective analysis was made on the clinical data of 60 NSCLC patients who were treated with immunotherapy combined with chemotherapy and bevacizumab after EGFR-TKIs treatment failure in the Affiliated Cancer Hospital of Shandong First Medical University from January 2019 to March 2022. Patients were followed up by telephone or outpatient review up to October 1, 2022, with a median follow-up of 8.2 months (95%CI: 7.1-9.3). All 60 patients were followed up. The response evaluation criteria in solid tumors were used to evaluate the short-term efficacy. The adverse reactions of patients were evaluated according to the common terminology criteria for adverse events. The survival curve was drawn by Kaplan-Meier method. Cox proportional hazard regression models were utilized to analyze the influencing factors of progression-free survival (PFS). Results: Among the 60 NSCLC patients, 22 were males. The age ranged from 41 to 75 years, with a median age of 61 years. Eleven patients had partial response, 19 patients had stable disease and 30 patients had progressive disease. The median PFS was 8.2 months (95%CI: 7.2-9.2). The median PFS of patients with low expression of programmed death receptor-ligand 1 (PD-L1) [Tumor cell Proportion Score (TPS)<1%], moderate expression of PD-L1 (1%≤TPS≤49%), and high expression of PD-L1 (TPS≥50%) were 6.4 (95%CI: 4.8-8.0), 8.3 (95%CI: 7.3-9.3) and 10.6 months (95%CI: 7.2-14.1), respectively, and there were statistically significant differences (χ2=13.58, P<0.001). Multivariate Cox proportional risk regression model analysis showed that age>65 years old (HR=4.017, 95%CI: 1.468-10.992, P=0.007) was a risk factor for PFS in NSCLC patients who received immunotherapy combined with chemotherapy and bevacizumab after EGFR-TKIs treatment failure. Moderate expression of PD-L1 (HR=0.360, 95%CI: 0.139-0.930, P=0.035) and high expression of PD-L1 (HR=0.155, 95%CI: 0.039-0.625, P=0.009) were protective factors for PFS. Most of the treatment-related adverse reactions in the whole group were grade 1-2, including bone marrow suppression (n=24), nausea (n=25), decreased appetite (n=24), fatigue (n=22), vomiting (n=18), abnormal liver function (n=17), blood creatinine increased (n=10), and so on. These were tolerated by the patients. Conclusions: NSCLC patients who failed EGFR-TKIs treatment can tolerate adverse reactions related to immunotherapy combined with chemotherapy and bevacizumab treatment. PFS is significantly prolonged in those aged≤65 years and those with moderate and high expression of PD-L1.

[The effects of high risk of ovarian hyperstimulation syndrome and duration of embryo cryopreservation on perinatal outcomes of single live births in the first frozen embryo transfer cycle after whole embryo cryopreservation].

Objective: To investigate the effects of high risk of ovarian hyperstimulation syndrome (OHSS) and duration of embryo cryopreservation on perinatal outcomes of the first frozen-thawed cycle after whole embryo cryopreservation. Methods: The clinical data of 1 804 patients who underwent the first frozen-thawed cycle after whole embryo cryopreservation and achieved singleton live births in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to June 2021 were retrospectively analyzed. According to whether there was high risk of OHSS in the oocyte retrieval cycle, the patients were divided into high-risk group (n=790) and non-high-risk group (n=1 014). The baseline data and perinatal outcomes were compared between the two groups. Multivariate linear regression was applied to analyze the relative factors affecting neonatal weight. And the high-risk group was divided into three subgroups according to different cryopreservation time: the embryos of 96 cycles with a cryopreservation time less than 60 days were defined as group A; the embryos of 587 cycles with a cryopreservation time around 60 to 120 days were defined as group B; the embryos of 107 cycles with a cryopreservation time more than 120 days were defined as group C. The perinatal outcomes were compared among the three groups. The measurement data in this study were represented byï¼»M（Q1，Q3）］. Results: The female age in the high-risk group was 30.0 (27.0, 32.0) years old, which was lower than that in the non-high-risk group 31.0 (29.0, 34.0) (P<0.001). The male age in high-risk group was 30.0 (28.0, 33.0), lower than that in non-high-risk group 32.0 (29.0, 35.0) (P<0.001). The birth weight of high-risk group [3 500.0 (3 200.0,3 800.0) g] was higher than that of control group [3 400.0 (3 150.0,3 800.0) g](P=0.045). Multivariate linear regression analysis showed that female BMI was correlated with neonatal weight, ß (95%CI) was 15.37(8.33, 22.41) (P<0.001), and the high risk of OHSS was not correlated with neonatal weight, ß (95%CI) was 19.40 (-38.07, 76.87) (P=0.508). There was significant difference in the incidence of low birth weight and very low birth weight among groups A, B and C (all P values<0.05), and the incidence of low birth weight and very low birth weight in group C was higher than that in group B (all P values<0.017). Conclusions: The risk of adverse perinatal outcomes in high-risk OHSS patients who underwent the first frozen-thawed cycle after whole embryo cryopreservation was not increased. However, prolonged cryopreservation of embryos may lead to increased risk of low birth weight and very low birth weight.

[Effect of preimplantation genetic testing for aneuploidies on pregnancy outcome in patients with unexplained recurrent spontaneous abortion].

Objective: To investigate the effect of preimplantation genetic testing for aneuploidies (PGT-A) on pregnancy outcome and perinatal outcome of single live birth in patients with unexplained recurrent spontaneous abortion (URSA). Methods: The clinical data of 351 cycles of the first transfer of a blastocyst through whole embryo freezing in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from 2019 to 2021 were retrospectively analyzed. According to whether PGT-A was performed before the transfer, the patients were divided into two groups: the PGT-A group (160 cycles) and the control group (191 cycles) were treated with in vitro fertilization/intracytoplasmic sperm microinjection (IVF/ICSI). To adjust for confounding factors, propensity score matching (PSM) was carried out in a 1∶1 ratio between the two groups of patients. After matching, 98 patients in the PGT-A group and 98 patients in the control group were compared for pregnancy outcome and perinatal outcome of singleton live births. Results: Before PSM, the female age in the PGT-A group was (33.6±4.0) years, lower than that in the control group (34.5±4.5) years (P=0.049). Male age in the PGT-A group was (33.6±4.1) years, lower than that in the control group (35.3±5.1) years (P<0.001). There were statistically significant differences between the two groups in infertility factors, female body mass index (BMI), years of infertility, number of spontaneous abortions, basal follicle stimulating hormone (FSH), endometrial thickness on the day of transfer and the percentage of high-quality blastocysts (all P values<0.05); After PSM, there was a statistically significant difference in fertilization methods and infertility factors between the two groups (P<0.05), while other differences were not statistically significant (all P values>0.05); There were statistically significant differences between the two groups in implant rate [63.3% (62 cycles) vs. 49.0% (48 cycles), P=0.044], clinical pregnancy rate [63.3% (62 cycles) vs. 49.0% (48 cycles), P=0.044], and live birth rate [42.9% (42 cycles) vs. 28.6% (28 cycles), P=0.037]. There was no statistically significant difference in perinatal outcomes between the PGT-A group and the control group in obtaining single birth live births (P>0.05). Conclusion: Compared with conventional IVF/ICSI assisted pregnancy, PGT-A assisted pregnancy significantly improves implantation rate, clinical pregnancy rate, and live birth rate in URSA patients. PGT-A improves the pregnancy outcomes in URSA patients but not perinatal outcomes in patients with singleton live births.

[Efficacy and short-term outcomes of myocardial protection using single-dose histidine-tryptophan-ketoglutarate cardioplegia during aortic root surgery with different duration of myocardial ischemia].

Objective: To explore the efficacy of myocardial protection with single-dose histidine-tryptophan-ketoglutarate (HTK) cardioplegia during aortic root operation, and the correlation between short-term clinical outcomes and duration of myocardial ischemia. Methods: The data of clinical cases undergoing myocardial protection with single-dose HTK cardioplegia during aortic root operation from January 2018 to December 2022 were retrospectively reviewed. Patients were divided into conventional HTK cardioplegia group (<3 h) and prolonged HTK cardioplegia group (≥3 h) according to duration of intraoperative myocardial ischemia. A 1∶1 propensity score matching was performed and the correlations between duration of myocardial ischemia and postoperative short-term outcomes (30-day mortality, readmission, mechanical circulation support and renal insufficiency) were analyzed. Results: A total of 282 patients were included in the final analysis, with 210 cases in the conventional HTK cardioplegia group and 72 cases inthe prolonged HTK cardioplegia group before matching. After matching, there were 64 cases (53 males and 11 females) in the conventional HTK cardioplegia group, with a mean age of (49.4±14.2) years. The prolonged HTK cardioplegia group had 64 cases (55 males and 9 females), with a mean age of (50.5±12.3) years. Higher sensitivity troponin [12 h: 10.1 (4.6, 18.7) µg/Lvs 4.1(2.2, 8.6) µg/L, P=0.002; 24 h: 7.7 (4.5, 19.0) µg/L vs 4.8 (2.2, 11.9) µg/L, P=0.025] and creatine kinase isoenzyme[12 h: 46.3 (28.1, 62.4) µg/L vs 20.7(14.1, 32.9) µg/L, P<0.001; 24 h: 26.3(13.4, 49.2) µg/L vs 14.5 (10.1, 33.5)µg/L, P=0.011] after surgery was detected in prolonged HTK cardioplegia group. Comparisons of other primary and secondary endpoint events showed no significant differences between the two groups (all P>0.05). Multivariate binary logistic regression showed that duration of myocardial ischemia had no significant effect on postoperative 30-day mortality (OR=1.255, 95%CI: 0.500-3.148, P=0.629), 30-day readmission (OR=0.378, 95%CI: 0.069-2.065, P=0.261) and mechanical circulation support (OR=0.991, 95%CI: 0.331-2.970, P=0.998). Conclusion: During aortic root surgery, single-dose HTK cardioplegia may provide satisfactory myocardial protection, and there was no significant correlation between duration of myocardial ischemia and short-term clinical outcomes.

Mathematical model and experiment analysis of pressure fluctuation inside dual-stack drainage system in residential buildings.

The final velocity was put forward to study the water flow characteristics inside the building drainage system; however, it is more suitable for low-rise and multi-storey buildings, not for high-rise buildings. This study revealed the drainage transient characteristics of a double stack drainage system in high-rise residential buildings. Based on the final velocity, the air-water interaction mechanism and two-phase flow conditions in high-rise residential drainage stacks were discussed. An influence model of drainage system flow rate on pressure fluctuation under the change of state parameters such as ventilation rate, pipe wall roughness and building height was established. The pressure limit and flow rate data were obtained through full-scale experiments. The pressure limit and flow rate model were simplified to Pn = A c Q2 + B c Q1:81 + C. After the data were verified, the fitting coefficients A, B and C were linear to the floor height.

[The effect of human chorionic gonadotropin day serum progesterone level on the live birth rate of fresh embryo transfer with GnRH antagonist protocols].

Objective: To investigate the effect of human chorionic gonadotropin (HCG)day serum progesterone (P) level on the live birth rate (LBR) of fresh embryo transfer with GnRH antagonist protocols. Methods: Patients who underwent the first IVF/ICSI in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were included for analysis. The patients with normal ovarian response with GnRH antagonist protocols were included (n=765). The receiver operating characteristic curve (ROC) was used to select the optimal cut-off value of serum P on HCG day (0.83 µg/L), and the included cycles were divided into two groups: P<0.83 µg/L (n=444) and P≥0.83 µg/L (n=321). The primary outcome measure was LBR. Secondary outcome measures included clinical pregnancy rate (CPR) and early miscarriage rate. The difference of the above indexes between the two groups was compared. Multivariate logistic regression model was used to analyze the effect of serum P level on LBR in fresh embryo transfer cycles. Results: The maternal ages in P<0.83 µg/L group and P≥0.83 µg/L group were (32.40±5.49) years and (32.53±5.51) yeas, respectively. The paternal ages were (33.35±6.34) years and (33.43±6.38) years, respectively of which, the difference was not statistically significant (P>0.05). The CPR in the P<0.83 µg/L group was 45.9% (n=204), which was significantly higher than that in the P≥0.83 µg/L group (37.1%) (n=119) (P=0.014). There was no significant difference in the early miscarriage rate between the two groups [14.2% (n=29) vs 14.3% (n=17), P=0.986]. The LBR in the P<0.83 µg/L group was significantly higher than that in the P≥0.83 µg/L group [36.3% (n=161) vs 28.0% (n=90), P=0.017]. By multivariate logistic regression model analysis, the maternal age, type of embryo transferred, number of embryos transferred, endometrial thickness on HCG day and serum P level on HCG day were independent risk factors of LBR. The adjust OR(95%CI) were 0.91(0.88-0.94), 2.36(1.04-5.35), 1.84(1.14-2.95), 1.16(1.07-1.25)and 0.63(0.44-0.89), all P<0.05. Conclusion: When the GnRH antagonist protocol is applied in the normal ovarian response population, as the serum P on the HCG trigger day≥0.83 µg/L, the CPR and LBR of fresh embryo transfer are decreased.

[Effectiveness, safety and cost of urinary follicle stimulating hormone in controlled ovarian stimulation in China: multi-center retrospective cohort study of 102 061 in vitro fertilization cycles].

Objective: To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China. Methods: Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use. Results: Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol (OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol (OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased (OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased (OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant (P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient (P<0.01). Conclusion: For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

[The clinical value of von Willebrand factor and VITRO score in evaluating disease progression in patients with HBV infection].

Objective: To explore the clinical value of von Willebrand Factor (vWF) and VITRO score (vWF:Ag/platelet count) in assessing disease progression in patients with HBV infection. Methods: Randomly collect relevant clinical data of 308 patients with HBV infection (including 154 cases of chronic hepatitis B, 66 cases of hepatitis B cirrhosis in compensatory period, 88 cases of hepatitis B cirrhosis in decompensated period) from December 1, 2018 to January 5, 2021 in the Second Affiliated Hospital of Chongqing Medical University. The vWF values are measured by a uniform optical method, and all data are included using a uniform standard. Analyze the difference and significance of plasma vWF level and VITRO score in chronic hepatitis B, hepatitis B cirrhosis in the compensatory phase and decompensated phase. Results: The plasma vWF level and VITRO score of the chronic hepatitis B group were (139.47±76.44) and (0.86±0.8), respectively, and the hepatitis B cirrhosis compensated group was (164.95±67.12 and 1.44±1.14), respectively. Hepatitis cirrhosis decompensated group were (317.48±103.32 and 6.81±4.98), respectively; plasma vWF level and VITRO score increased with the progression of HBV infection, and the difference was statistically significant (F=133.669,P=0.000F=137.598,P=0.000).The plasma vWF level and VITRO score in patients with hepatitis B cirrhosis were (185.65±85.07 and 2.3±2.37) in the Child-Pugh A group, (304.74±105.81 and 6.37±5.19) in the B grade group, and (369.48±73.238.28±5.38) in the C grade group; plasma vWF level and VITRO score in patients with hepatitis B cirrhosis increased with the increase of Child-Pugh grade, and the difference was statistically significant (F=60.236, P=0.000F=32.854, P=0.000). The area under the curve (AUC) of plasma vWF level and VITRO score for diagnosing the decompensated stage of hepatitis B cirrhosis were 0.897 [95% confidence interval (CI): 0.855-0.940, P＜0.01], 0.949 [95% CI: 0.916-0.982, P＜0.01). When the vWF level and VITRO score were taken as cut-off values of 238.5% and 1.65, respectively, the sensitivity of diagnosing the decompensated stage of hepatitis B cirrhosis was 79.5% and 94.3%, the specificity was 92.3% and 87.7%, and the positive predictive value was 80.5% and 94.3%, the negative predictive value was 91.9% and 97.5%, and the diagnostic accuracy was 88.6% and 89.3%. Among the patients with decompensated hepatitis B cirrhosis, the level of vWF in the group with gastrointestinal bleeding (367.24±68.29)% was significantly higher than that in the group without gastrointestinal bleeding (286.15±109.69)%, and the difference was statistically significant (P＜0.001) The VITRO score of the group with gastrointestinal bleeding (9.12±5.4) was significantly higher than that of the group without gastrointestinal bleeding (5.36±4.13), and the difference was statistically significant (P＜0.01). The vWF level in the spontaneous peritonitis group was (341.73±87.92)% higher than that in the non-spontaneous peritonitis group (296.32±111.74)%, and the difference was statistically significant (P＜0.05). There was no statistical difference in VITRO score between the two groups. significance. Conclusion: Plasma vWF level and VITRO score can evaluate the progression of liver disease and the degree of decompensation of liver cirrhosis in patients with HBV infection, and have a predictive effect on various complications after decompensation of liver cirrhosis, and have certain guiding significance for early intervention measures.

[Discussion on relevant issues of Technical Specifications for Occupational Health Surveillance (GBZ 188-2014)].

Technical Specifications for Occupational Health Surveillance (GBZ 188-2014) is an important basis for judging suspected occupational diseases and occupational contraindications. There are crossing over or overlap between occupational contraindications and diagnostic criteria of poisoning damage. Occupational contraindications have different meanings with the degree and range of common diseases or symptoms and the frequency of physical examination during employment conflicts with the current standard. Based on the practice of occupational health examination in a large population, the present study analyzed relevant articles and put forward some suggestions for revision, in combination with clinical medicine, occupational health standards, and diagnostic standards of occupational diseases. The modification could provide a reference for the revision of Technical Specifications for Occupational Health Surveillance and the practice of occupational health examination.

Test of Lepton-Flavor Universality in B→K

We present a measurement of R_{K^{*}}, the branching fraction ratio B(B→K^{*}µ^{+}µ^{-})/B(B→K^{*}e^{+}e^{-}), for both charged and neutral B mesons. The ratio for the charged case R_{K^{*+}} is the first measurement ever performed. In addition, we report absolute branching fractions for the individual modes in bins of the squared dilepton invariant mass q^{2}. The analysis is based on a data sample of 711 fb^{-1}, containing 772×10^{6} BB[over ¯] events, recorded at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The obtained results are consistent with standard model expectations.

ClyA enhances LPS-induced IL-1ß secretion in human macrophages through TLR4 and NLRP3 signaling.

Lipopolysaccharide (LPS) plays an important role in tumor suppression by activating macrophages. After macrophages activation, a trail of cytokines was secreted, including IL-1ß. Previous studies reported that the anti-tumor function of IL-1ß is concentration-dependent, and increasing the level of IL-1ß will enhance its anti-tumor effect. Cytolysin A (ClyA), a member of the protein family called pore-forming toxins (PFTs), is secreted by Gram-negative bacteria, which has a potential role in enhancing the secretion of IL-1ß. In this study, the function of Cytolysin A was evaluated by investigating its ability to induce innate immune responses in macrophages and the signaling pathway(s) involved in LPS-induced production of IL-1ß. The production of IL-1ß was highly enhanced when the macrophages were treated with LPS and ClyA together. The production of IL-1ß was regulated by TLR4-MyD88-IL-1ß pathway and NLRP3-ASC-Caspase1-IL1ß pathway. By treating the colon cancer cell line CT26 with the conditioned medium, the proliferation of CT26 cells was inhibited and the apoptosis of CT26 cells was increased. In conclusion, this study indicated that ClyA enhances the production of IL-1ß induced by LPS in human macrophages. The proliferation of CT26 cells was inhibited and the apoptosis was increased when being treated with the macrophage-conditioned media, which provides a feasible treatment for colon tumor.

CT phenotypes in mild-to-moderate chronic obstructive pulmonary disease: difference before and after the age of 60 years.

AIM: To investigate the pulmonary phenotype of mild-to-moderate chronic obstructive pulmonary disease (COPD) using quantitative computed tomography CT analysis techniques. MATERIALS AND METHODS: Sixty-three patients with stable-phase mild-to-moderate COPD and 78 healthy controls, categorised as those aged <60 (28 and 40 patients, respectively) and ≥60 years (35 and 38, respectively), underwent chest low-dose respiratory dual-phase CT and pulmonary function test. Automatic software was used to measure the proximal airway parameters, and the emphysema and air-trapping indices were recorded. The intergroup differences in each parameter were assessed by one-way analysis of variance. RESULTS: At <60 years of age, the mean Pi10WA (Wall area of a hypothetical airway with an internal perimeter of 10 mm) was greater in the mild-to-moderate COPD group than in the healthy control group (17.04 ± 1.63 versus 16.03 ± 1.16 mm2; p=0.004). Mild or moderate air-trapping was observed in the mild-to-moderate COPD group aged <60 years. There was no significant difference in the proximal airway parameters and inspiratory VI-950 (percent voxels less than -950 HU) between the two groups at age ≥60 years (all p>0.05); however, the expiratory VI-856 (percent voxels less than -856 HU) and mean lung density expiratory/inspiratory ratio (MLDE/I) were higher in the mild-to-moderate COPD group than those in the healthy control group (26.02 [30.23] versus 6.45 [11.16]; 0.88 ± 0.05 versus 0.84 ± 0.04; p<0.001 and p=0.024). CONCLUSION: For patients with mild-to-moderate COPD, the CT phenotype was predominantly the "airway remodelling" type at <60 years of age, and the "air-trapping" type at ≥60 years of age. Thus, pulmonary CT phenotypes of mild-to-moderate COPD patients of different age groups are different.

The safety and efficacy of transarterial chemoembolisation with bleomycin for hepatocellular carcinoma unresponsive to doxorubicin: a prospective single-centre study.

AIM: To investigate the safety and efficacy of transarterial chemoembolisation (TACE) with bleomycin for hepatocellular carcinoma (HCC) unresponsive to doxorubicin. MATERIALS AND METHODS: A randomised controlled trial was undertaken of HCC patients resistant to TACE with doxorubicin to assess the survival benefits of the experimental group (TACE with bleomycin) compared with the control group (TACE with doxorubicin). One hundred and seventy patients were allocated randomly between December 2015 and December 2017, and 80 patients of each group were analysed. The modified response evaluation criteria in solid tumours (mRECIST) was used to evaluated the tumour response every 4-6 weeks. The primary endpoint was median progression-free survival (mPFS) and median overall survival (mOS). Safety was assessed by post-procedure complications. RESULTS: The study was completed in October 2018. Objective response rate (ORR) of the experimental group was 27.5% (22/80), mPFS and mOS was 5.8 and 8.1 months. ORR of the control group was 7.5% (6/80), mPFS and mOS was 2.9 and 4 months. The ORR were significantly different between two groups (χ2 = 0.348, p<0.05). The differences of mPFS and mOS between the two groups were statistically significant (χ2 = 2.865, p<0.05 and χ2 = 0.926, p<0.05, respectively). There were no significant difference in post-procedure complications (p>0.05) and no major complications occurred. CONCLUSION: It is suggested that TACE with bleomycin is a safe and effective method for HCC and bleomycin can be a second-line chemotherapeutic agent for the HCC patients unresponsive to TACE with doxorubicin.