Background::Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods::We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT.Results::Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death.Conclusion::The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration::ClinicalTrials.gov, NCT02879526.

Objective:To investigate the influence of maternal autoimmune diseases and anticoagulants, including low-molecular-weight heparin (LMWH) and aspirin, on the fetal fraction of maternal plasma cell-free DNA of non-invasive prenatal testing (NIPT).Methods:A prospective cohort study was conducted on women with singleton pregnancies receiving NIPT in the Nanjing Drum Tower Hospital from March 2021 to July 2022. NIPT was carried out using a polymerase chain reaction (PCR)-free amplification platform. In this study, four types of maternal autoimmune diseases, which were antiphospholipid syndrome, undifferentiated connective tissue disease, Sj?gren's syndrome, and systemic lupus erythematosus (SLE), and two anticoagulants, LMWH and aspirin, were studied. Univariate and multivariate linear regression models were used to analyze the factors influencing fetal fraction of maternal plasma cell-free DNA.Results:A total of 4 102 singleton pregnant women were enrolled in the prospective cohort, and 3 948 were finally included after excluding the cases with unclear dosing time of LMWH or aspirin, other autoimmune diseases, conceiving through ovulation induction alone, and having true positive or failed NIPT result. There were 96 cases with antiphospholipid syndrome, 35 with undifferentiated connective tissue disease, 34 with Sj?gren's syndrome, and 18 with SLE. A total of 108 patients only received LMWH treatment, 121 only received aspirin treatment, and 113 received both LMWH and aspirin treatment. Univariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.423), conceived by assisted reproductive technology ( B=－0.803), male fetus ( B=－0.458), undifferentiated connective tissue disease ( B=1.774), and SLE ( B=3.467) had influence on the fetal fraction (all P<0.05). Multivariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.415), conceived by assisted reproductive technology ( B=－0.585), male fetus ( B=－0.322), SLE ( B=3.347) and undifferentiated connective tissue disease ( B=1.336) were factors influencing fetal fraction (all P<0.05). Conclusions:Maternal use of LMWH or aspirin does not affect fetal fraction when performing NIPT on a PCR-free amplification platform, but undifferentiated connective tissue disease and SLE are the influencing factors. Therefore, pregnant women should be informed before the NIPT that the fetal fraction of maternal plasma cell-free DNA may be affected by maternal autoimmune diseases.

Objective:To learn about the iodine nutrition level and its spatial distribution status in key populations in Hubei Province, so as to provide a basis for adjustment of iodine supplementation policy and the realization of scientific and accurate iodine supplementation.Methods:In 2020, a sampling was carried out in Hubei Province according to the "National Iodine Deficiency Disorders Monitoring Plan (2016 Edition)" to monitor the concentration of salt iodine and urinary iodine of key populations (children ages 8 - 10 years old and pregnant women). The spatial distribution of iodine nutrition levels was analyzed by spatial epidemiology.Results:The median salt iodine of 17 263 children's family salt samples was 25.0 mg/kg, and the median urinary iodine (MUI) was 217.0 μg/L. There was significant spatial aggregation in the distribution of urinary iodine level in children at the county level ( Moran's Index = 0.36, P < 0.001). The significant hot spot areas with high urinary iodine level among children were located in Shiyan City and Xiangyang City, while the significant cold spot areas with low urinary iodine level were mainly concentrated in Yichang City. The median salt iodine of 8 618 pregnant women's family salt samples was 25.1 mg/kg, the MUI was 176.3 μg/L. The urinary iodine level among pregnant women at the county level was spatially clustered ( Moran's Index = 0.22, P = 0.003) . The significant hot spot areas with high urinary iodine level among pregnant women were mainly in Enshi Tujia and Miao Autonomous Prefecture, the significant cold spot areas were mainly concentrated in Yichang City. Conclusions:In 2020, the iodine nutrition of children in Hubei Province is at a super appropriate level (200 - 299 μg/L), and the iodine nutrition status of pregnant women is more sensitive, which is close to the lower limit of the appropriate level (150 μg/L). The urinary iodine level of children and pregnant women has significant spatial aggregation at the county level. Targeted intervention will be needed in counties (dictricts) where the urinary iodine level is lower or higher than the normal range, to achieve accurate and scientific iodine supplementation.

ObjectiveThis study aimed to understand the epidemiological characteristics of hand-foot-mouth disease （HFMD） in Minhang District， Shanghai from 2009 to 2020， and provide a scientific basis for the prevention and control of HFMD. MethodsThe case information of HFMD was collected from the National Notifiable Infectious Diseases Reporting System of Chinese Center for Disease Control and Prevention. We used descriptive epidemiological methods to analyze the population characteristics， temporal and spatial distribution of HFMD， the pathogen composition of the case and its changing trend. ResultsFrom 2009 to 2020， a total of 66，198 cases of HFMD were reported in Minhang District， Shanghai， including 377 severe cases （severe case rate 0.57%） and 3 deaths （severs case fatality rate 0.80%）. There were more cases of HFMD in boys than in girls （1.5∶1）. HFMD patients aged under 5 years predominated， accounting for 88.91% of all cases. Majority of the cases （91.42%） were in scattered children （55.80%） and children in kindergartens （35.62%）. The incidence showed a cyclical trend， with low incidence years and high incidence years appearing alternately. The peak period was from April to July， and sometimes there were small peaks during October to December. A total of 12 years time-space scanning analysis revealed 3 clusters. The cluster centers were located in Wujing Town， Huacao Town and Xinzhuang Town， respectively. The proportion of EV71 in common cases was generally decreasing， and reduced to zero in 2019. The proportion of CoxA6 had increased year by year， and reached 75.00% in 2020. CoxA6 became the dominant pathogen in recent years. The number of severe cases had decreased year by year since 2010， and the dominant pathogen was EV71 （90.03% on average） in severe cases. ConclusionThe incidence of HFMD in Minhang District of Shanghai has a downward trend from 2014. The dominant pathogen changes from EV71 to CoxA6， and the dominant pathogen in severe cases is EV71. The discovered temporal and spatial clustering pattern is helpful for in-depth understanding of the distribution and epidemic trend of HFMD in Minhang District， and provides a scientific basis for epidemic prevention and control.

Objective:To explore the clinical features and survival of newly diagnosed follicular lymphoma (FL) patients with diffuse large B-cell lymphoma (DLBCL) component.Methods:1845 newly diagnosed FL patients aged ≥ 18 years with grades 1-3a in 11 medical centers in China from 2000 to 2020 were included, and patients with DLBCL component were screened. The clinical data and survival data of the patients were retrospectively analyzed, and the prognostic factors were screened by univariate and multivariate analysis.Results:146 patients (7.9% ) with newly diagnosed FL had DLBCL component. The median age was 56 (25-83) years, 79 males (54.1% ) . The pathology of 127 patients showed the proportion of DLBCL component. Patients were divided into two groups according to whether the proportion of DLBCL component was ≥ 50% . The study found that patients with DLBCL component ≥ 50% had higher grade 3 ratio (94.3% vs 91.9% , P=0.010) , Ki-67 index ≥ 70% ratio (58.5% vs 32.9% , P=0.013) and PET-CT SUVmax ≥ 13 ratio (72.4% vs 46.3% , P=0.030) than patients with DLBCL component<50% . All patients received CHOP or CHOP like ± rituximab chemotherapy. The overall response rate (ORR) was 88.2% , and the complete response (CR) rate was 76.4% . In the groups with different proportions of DLBCL component, there was no significant difference in the remission rate after induction treatment and the incidence of disease progression within 2 years after initiation of treatment (POD24) ( P<0.05) . The overall estimated 5-year progression free survival (PFS) rate was 58.9% , and the 5-year overall survival (OS) rate was 90.4% . The 5-year OS rate of POD24 patients was lower than that of non POD24 patients (70.3% vs 98.5% , P<0.001) . Compared with non maintenance treatment of rituximab, maintenance treatment of rituximab could not benefit the 5-year PFS rate (57.7% vs 58.8% , P=0.543) , and the 5-year OS rate had a benefit trend, but the difference was not statistically significant (100% vs 87.8% , P=0.082) . Multivariate analysis showed that failure to reach CR after induction treatment was an independent risk factor for PFS ( P=0.006) , while LDH higher than normal was an independent risk factor for OS ( P=0.031) . Conclusion:FL patients with DLBCL component ≥50% have more invasive clinical and pathological features. CHOP/CHOP like ± rituximab regimen can improve the clinical efficacy of patients. Rituximab maintenance therapy can not benefit the PFS and OS of patients. Failure to reach CR after induction therapy was the independent unfavorable factor for PFS.

Objective:To study the influence of different feeding patterns on mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in pregnant women with high viral loads who received antiviral medication during pregnancy to the day of delivery.Methods:This prospective cohort study was conducted in Beijing You'an Hospital. From January 1, 2019, to March 31, 2020, and 574 pregnant women with positive hepatitis B surface antigen (HBsAg) and HBV DNA>2×10 5 IU/ml were enrolled. All participants received tenofovir, telbivudine, lamivudine, or propofol tenofovir from 24-28 weeks of gestation and discontinued on the day of delivery, and their neonates were postnatally given routine passive-active immunoprophylaxis. Based on the feeding patterns, the subjects were divided into three groups: breastfeeding ( n=257), bottle-feeding ( n=241) and mixed feeding groups ( n=76). The follow-up data were obtained from liver functions and HBV DNA level of the mothers at 6-8 weeks postpartum and HBV serological markers of infants at 7-12 months. One-way ANOVA, Student-Newman-Keuls, Chi-square test or Fisher exact test, and repeated measures ANOVA were used to analyze the data. Results:The average maternal HBV DNA levels before antiviral treatment did not differ significantly between the three groups [(7.90±0.67), (7.82±0.70), (7.83±0.70) log 10 IU/ml, F=0.912, P>0.05]. HBV DNA level before delivery in the mixed feeding group was slightly lower than that in the breastfeeding and bottle-feeding group [(3.87 ±1.08) vs (4.21±1.17) and (4.30±1.28) log 10 IU/ml, q= 3.052 and 3.831, both P<0.05], while the comparison between the latter two groups showed no significant differences ( P>0.05). After delivery, HBV DNA level in the bottle-feeding group was slightly lower than that in the breastfeeding group [(7.42±0.93) vs (7.69±0.90) log 10 IU/ml, q=4.583, P<0.05]. Among 580 infants (including six pairs of twins), only one bottle-fed infant (0.4%, 1/243) was infected with HBV through MTCT, and none in the breastfeeding or mixed feeding group ( P=0.553). Conclusions:For pregnant women with high viral loads of HBV who have received antiviral medication during pregnancy, although HBV DNA level will rebound after discontinuation upon delivery, breastfeeding is recommended considering it does not increase the risk of MTCT.

Objective:To evaluate the intrauterine transmission of syphilis in Nantong City, Jiangsu Province from 2012 to 2019, after the introduction of a nationwide policy for preventing intrauterine transmission of syphilis in China in 2011.Methods:This study enrolled all live birth deliveries ( n=455 561) in Nantong from January 2012 to December 2019. The screening, infection rates, anti-syphilis treatment, intrauterine transmission of syphilis, and outcomes of infants with congenital syphilis were retrospectively analyzed using χ 2 test for trend, adjusted χ 2 test, or Fisher's exact test. Results:Except for three women, the remaining 455 558 subjects were all screened for syphilis antibody with a total screening rate of nearly 100%, among which prenatal screening accounted for 96.4% (439 125/455 561) and intrapartum screening for 3.6% (16 433/455 561). In total, 796 (0.17%) women were diagnosed with syphilis during pregnancy, and the prevalence increased from 0.13% (85/64 229) in 2012 to 0.24% (110/45 517) in 2019 (χ 2trend=48.985, P<0.001). The prevalence among women underwent intrapartum screening was significantly higher than those underwent prenatal screening [0.50% (82/16 433) vs 0.16% (714/439 125), χ 2=102.769, P<0.001]. Out of the women with syphilis, 716 (89.9%) received anti-syphilis therapy with 695 cases using penicillin, 16 cases using ceftriaxone and five using erythromycin/azithromycin, while the remaining 80 (10.1%) did not. Intrauterine transmission of syphilis occurred in 14 infants with a transmission rate of 1.8% (14/796). The reported rate of congenital syphilis in all live infants was 0.03‰ (14/460 552). The intrauterine transmission rate in women receiving treatment during pregnancy was significantly lower than that in the untreated women [0.4% (3/716) vs 13.8% (11/80), χ2=66.499, P<0.001]. For the untreated women, the intrauterine transmission rate increased with the rising titers of non-specific syphilis antibody ( χ2trend=5.338, P=0.021). Among infants with congenital syphilis, no obvious adverse outcomes occurred in three infants born to treated mothers, whereas the rates of preterm birth and neonatal death were 7/11 and 2/11 in those born to untreated mothers. Conclusions:Since the implementation of the policy against intrauterine transmission of syphilis, the reported rate of congenital syphilis is 3/100 000 live-birth in Nantong City, reaching the national target of below 15/100 000. Screening and treatment in the first trimester are critical for preventing intrauterine transmission of syphilis. Increased prenatal syphilis screening rate can help further reduction of the intrauterine transmission of syphilis.

As a kind of skills clinical medical students must master, the basic teaching of operative surgery is relatively backward in teaching mode and means, thus negatively affecting the teaching effect. The virtual reality is applied to the basic teaching of operative surgery, and the pre-designed course contents are presented in a situational way, so that students can experience the immersive learning style. It changes the classroom roles, gives full play to the advantages of virtual reality, and makes up the disadvantage of traditional education mode, finally improving the training effect.

AIM: To guide the multiple imputation of missing data in clinical longitudinal studies and its sensitivity analyses, and highlight the importance of sensitivity analyses by taking the clinical trial of Qizhitongluo Capsule in treating ischemic stroke as an example. METHODS: To implement PROC MI process in SAS to perform multiple imputation and its sensitivity analysis. RESULTS: In the example, after multiple imputation, improvements in lower limb motor scores of the Qizhitongluo group were greater than those of the placebo group (all P<0.01), and the results of two sensitivity analyses under "missing not at random" were consistent with those under "missing at random". CONCLUSION: Multiple imputations combined with sensitivity analyses can ensure a robust result. It is recommended that clinical researchers perform sensitivity analyses after filling missing data.

This study was a single-center large-sample case-control study.Data of 1 106 elderly patients who underwent unilateral total hip arthroplasty from June 2013 to May 2019 were collected, including items such as patient′s baseline characteristics, comorbidities, perioperative medication, intraoperative blood pressure, and postoperative outcomes.Patients were divided into postoperative nausea and vomiting(PONV)group and non-PONV group according to whether nausea and vomiting occurred within 24 h after operation.Logistic regression analysis was used to determine the risk factors for PONV.The incidence of PONV was 11.03%.Female, intraoperative use of dezocine, and intraoperative hypotension(duration>3 min or cumulative time>6 min)are independent risk factors for PONV, while femoral neck fractures and intraoperative use of dexamethasone are protective factors.