CT radiomics combined with clinical and CT features for predicting TNM stage of thymic epithelial tumor / 中国介入影像与治疗学

Objective To explore the value of CT radiomics combined with clinical data and CT features for predicting TNM stage of thymic epithelial tumor(TET).Methods Data of 216 single TET patients confirmed by surgical pathology were retrospectively analyzed.Totally 151 cases with TNM stage Ⅰ TET were divided into early group,while 27 with TNM stage Ⅲ and 38 with TNM stage Ⅳ TET were divided into late group(n=65).Univariate analysis was used to analyze clinical data and chest CT manifestations.Based on non-contrast-enhanced CT(NECT)and contrast-enhanced CT(CECT),the best radiomics features were extracted and screened to establish radiomics models(RMNECT,RMCECT)for predicting TNM stage of TET.RMNECT-clinic,RMCECT-clinic,RMNECT-clinic-CT and RMCECT-clinic-CT were constructed based on combination of clinical and CT features being significantly different between groups,respectively.The patients were divided into training set(n=151)and validation set(n=65)at the ratio of 7∶3.The above models were trained in the training set using repeated 5-fold cross validation method,and their efficacy were verified in the validation set.Results Significant differences of clinical symptoms and CT manifestations including fat infiltration around the lesion,mediastinal lymph node enlargement and pleural effusion were found between groups(all P＜0.05).Based on NECT and CECT,2 and 9 best radiomics features were selected to construct the corresponding models.In validation set,the area under the curve(AUC)of RMNECT-clinic-CT for predicting TNM stage of TET(0.864)was higher than that of RMNECT and RMNECT-clinic(AUC=0.634,0.721,Z=3.081,2.937,P=0.002,0.003),while AUC of RMCECT-clinic-CT(0.920)was also higher than that of RMCECT and RMCECT-clinic(AUC=0.689,0.751,Z=2.698,2.390,P=0.007,0.017).Conclusion CT radiomics combined with clinical data and CT features could effectively predict TNM stage of TET.

Study on the Mechanism of Guanyuan Mingmen Sequential Acupuncture Activating FSHR/cAMP/PKA Pathway to Promote Granulosa Cell Proliferation in POI Model Rats / 广州中医药大学学报

Objective To observe the therapeutic effects and mechanisms of Guanyuan Mingmen Sequential Acupuncture on rats with premature ovarian insufficiency(POI)model.Methods Female SD rats were divided into the blank group,the model group,the protein kinase A(PKA)inhibitor(H89)+acupuncture group,and the acupuncture group,with 12 rats in each group.Except for the blank group,the POI model was prepared by gavage with Tripterygium Glycosides Tablets in the other three groups of rats.After the model was successfully established,the blank group and the model group were bundled once a day;in the acupuncture group,Guanyuan(RN4)point was taken during the intermotility period,and in the pre-motility period,Mingmen(DU4)point was taken;in the H89+acupuncture group,the intervention was performed in accordance with the acupuncture protocol of the acupuncture group,and H89 was injected intraperitoneally for 30 minutes prior to each acupuncture session.Continuous intervention was performed for 20 days.Samples were taken from each group of rats in the first estrus period and in proestrus period after intervention.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of follicle stimulating hormone(FSH)and estradiol(E2)during the estrous phase,Western Blot was used to measure the protein expressions of follicle stimulating hormone receptor(FSHR)and aromatase P450(P450arom)during the estrous phase,and the activity of granulocytes during the estrous phase and the proestrus phase were measured using the cell-counting kit 8(CCK-8)method.The immunohistochemistry method was used to detect the protein expression of pre-motility proliferating cell nuclear antigen(PCNA).Results(1)Compared with the blank group,the serum FSH level of the model group and H89+acupuncture group was significantly increased(P＜0.01),and the E2 level was significantly decreased(P＜0.001);there was no difference between the FSH level of the H89+acupuncture group and that of the model group(P＞0.05),and the E2 level of the H89+acupuncture group was lower than that of the model group(P＜0.05);the FSH level of the acupuncture group was lower than that of the model group and that of the H89+acupuncture group(P＜0.05),had no difference with the blank group(P＞0.05),E2 level was significantly higher than the model group and H89+ acupuncture group(P＜0.01),still being lower than the blank group(P＜0.05).(2)The protein expressions of FSHR and P450arom in the model group and H89 + acupuncture group was lower than those in the blank group;the protein expression of FSHR in the H89 + acupuncture group was not different from that in the model group(P＞0.05),while the protein expression level of P450arom was lower than that in the model group(P＜0.05);the protein expression levels of FSHR and P450arom in the acupuncture group were higher than those in the model group and H89 + acupuncture group,but still lower than those in the blank group(P＜0.05).(3)Both GCs activity and average optical density value of PCNA in the model group and H89+acupuncture group were lower than the blank group(P＜0.05);both GCs activity and average optical density value of PCNA in the H89+acupuncture group were lower than the model group(P＜0.05);the activity of GCs and average optical density value of PCNA of the acupuncture group were significantly higher than that of the model group and H89+acupuncture group(P＜0.05 or P＜0.01).Conclusion Guanyuan Mingmen Sequential Acupuncture can regulate sex hormone levels,increase GCs activity and promote GCs cell proliferation by up-regulating protein expressions of follicle stimulating hormone receptor(FSHR)/cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)pathway FSHR,P450arom,thus improving POI.

Durable remission related to CAR-T persistence in R/R B-ALL and long-term persistence potential of prime CAR-T.

CD19-targeted chimeric antigen receptor T lymphocytes (CAR-T) has demonstrated a high proportion of complete remission in the treatment of relapsed refractory acute B cell lymphoblastic leukemia (r/r B-ALL). It is of great clinical significance to explore which factors will impact long-term disease-free survival of patients with r/r B-ALL after CAR-T therapy without bridging bone marrow transplantation. Our study found that, in patients with r/r B-ALL without bridging transplantation, the patients' age; infusion dosage; whether they had undergone allo-stem cell transplantation before CAR-T therapy, using CD-19-targeted or CD19/CD22-dual-targeted CAR-T; whether there is fusion gene; tumor burden before therapy; and comorbidity had no significant relationship with their long-term disease-free survival. We found only that CAR-T persistence was highly correlated with patients' long-term disease-free survival. So, we further profiled CAR-T cells using single-cell sequencing and found that there is a specific T cell subset that may be associated with the long-term persistence of CAR-T. Finally, according to the single-cell sequencing results, we established cell production process named PrimeCAR, which shared common signaling pathways with the T cell subset identified. In the preliminary clinical study, prime CAR-Ts yield good persistence in peripheral blood of patients with B-ALL and lymphoma, without observing grade 2 or higher cytokine release syndrome.

Lung Imaging Evaluation in Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation / 中国医学影像学杂志

Purpose To analyze the abnormal CT imaging features of the lungs of adult patients with chronic graft-versus-host disease(cGVHD)and to improve the ability of diagnosis and differentiation of abnormal cGVHD lungs via combining with clinical data.Materials and Methods A retrospective study of 162 patients with clinical manifestations of cGVHD after allogeneic hematopoietic stem cell transplantation in Peking University People's Hospital from October 2018 to October 2020 was conducted.The chest CT images(including lesion location,distribution,ground glass density,consolidation,mesh image,nodule image,bronchiectasis,pleural effusion,gas retention,pneumothorax or mediastinal air)were summarized and the differences of imaging features between pulmonary cGVHD and pulmonary infection were compared.Results Of the 50 fungal infections,43 had single nodules;of the 7 viral infections,4 had diffuse ground glass nodules;2 had diffuse grid shadows,and of the 5 bacterial infections,1 had limited solid shadows.The 36 cases of non-infectious pulmonary complications were all oblusive bronchiolitis,and the CT signs showed gas retention in 32 cases,bronchiectasis in 22 cases,and thickening of the bronchial wall in 27 cases.Conclusion The vast majority of cGVHD patients have abnormal lung imaging,with the main cause of infection.Some patients have imaging manifestations of obliterated bronchiolitis,and imaging combined with clinical practice may be helpful for the diagnosis and differentiation of lung complications.

Genetic characterization of varicella-zoster virus in people aged 20 years and under in Yichang City of Hubei Province, 2019-2020 / 中华流行病学杂志

Objective: To analyze the genetic characteristics of varicella-zoster virus (VZV) in people aged 20 years and under in Yichang City of Hubei Province from 2019 to 2020. Methods: Based on the Yichang Health Big Data Platform, we investigated cases 20 and under clinically diagnosed as herpes zoster in three hospitals from March 2019 to September 2020. Collecting vesicle fluid and throat swab samples of the cases and completing questionnaires to obtain basic information. Real-time fluorescent quantitative PCR was used for positive identification of the virus. PCR amplification of VZV's open reading frame (ORF) and sequencing of the products to determine the VZV genotype. Analyze mutations at some specific single nucleotide polymorphism (SNP) sites. Results: Among 46 cases of herpes zoster, the male to female ratio was 1.3∶1 (26∶20) and the age ranged from 7 to 20 years old. Fifteen cases had been vaccinated against varicella, including 13 and 2 cases of 1 and 2 doses, respectively. VZV strains were detected in 34 samples (73.91%), all belonging to Clade 2. Phylogenetic tree analysis of the nucleotide of ORF22 showed, compared with Clade 2 referenced strains, the sequence matching degree of nucleotide for all 34 samples was 99.0% to 100.0%. Conclusion: The main VZV strain causing herpes zoster in people aged 20 years and under in Yichang from 2019 to 2020 was Clade 2.

Immediate analgesic effect of electroacupuncture combined with diclofenac sodium on acute gouty arthritis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the immediate analgesic effect of electroacupuncture (EA) combined with diclofenac sodium on acute gouty arthritis (AGA).@*METHODS@#A total of 90 patients with AGA were randomly divided into a low-dose medication (LM) group (30 cases, 1 case was eliminated, 1 case dropped off), a conventional medication (CM) group (30 cases, 1 case dropped off) and a combination of acupuncture and medication (AM) group (30 cases ). The LM group was given oral administration of 50 mg diclofenac sodium sustained-release capsule; the CM group was given oral administration of 100 mg diclofenac sodium sustained-release capsule; on the basis of the treatment of LM group, the AM group was treated with electroacupuncture at ashi points, Dadu (SP 2), Taichong (LR 3), Taibai (SP 3), Neiting (ST 44), Sanyinjiao (SP 6), Zusanli (ST 36) and Yinlingquan (SP 9) on the affected side, and Taichong (LR 3) and Zusanli (ST 36), Sanyinjiao (SP 6) and Yinlingquan (SP 9) were connected to electroacupuncture respectively, continuous wave, 2 Hz in frequency. The visual analogue scale (VAS) scores of pain before treatment and after 10 min, 2 h, 4 h and 6 h of treatment completion, joint tenderness and swelling scores before treatment and after 10 min and 6 h of treatment completion were compared, and the rate of diclofenac sodium addition within 24 h after treatment completion was recorded among the three groups.@*RESULTS@#After 10 min of treatment completion, the scores of VAS, joint tenderness and joint swelling in the AM group were lower than those before treatment (P<0.05), and the VAS score in the AM group was lower than that in the other two groups (P<0.05). After 2, 4 and 6 h of treatment completion, the VAS scores of the three groups were lower than those before treatment (P<0.05), and the scores in the AM group were lower than those in the LM group (P<0.05). After 6 h of treatment completion, the joint tenderness scores of the three groups and the joint swelling scores of the AM group and the CM group were lower than those before treatment (P<0.05), and the joint tenderness and swelling scores of the AM group were lower than those of the LM group (P<0.05). The rate of diclofenac sodium addition was 3.3 % (1/30) and 3.4 % (1/29) in the AM group and the CM group, respectively, which were lower than 17.9% (5/28) in the LM group (P<0.05).@*CONCLUSION@#Electroacupuncture combined with diclofenac sodium have a good immediate analgesic effect in the treatment of AGA, and have the advantages of small dosage of analgesic drugs and less adverse reactions.

Chemical constituents from whole herb of Hedyotis scandens / 中国中药杂志

This study aimed to investigate the chemical constituents in the water extract of the whole herb of Hedyotis scandens by silica gel, ODS, and MCI column chromatographies together with preparative high-performance liquid chromatography(HPLC). The structures of isolated constituents were identified by NMR, HR-ESI-MS, etc. Thirteen compounds were isolated and identified as methyl 4-benzoyloxy-3-methoxybenzeneacetate(1), 4-benzoyloxy-3-methoxybenzeneacetic acid(2), 3-(4-hydroxy-3-methoxyphenyl)-propanoic acid(3), salicylic acid(4), 3-hydroxy-4-methoxypyridine(5), syringic acid(6), hydroxycinnamic acid(7),(R)-6-methyl-4,6-bis(4-methylpent-3-enyl)cyclohexa-1,3-dienecarbaldehyde(8), 1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(9), 1H-indole-3-carboxaldehyde(10), isoscopoletin(11), syringaresinol(12), and pinoresinol(13). Among them, compounds 1 and 2 were new phenolic acid compounds, compounds 3-5, 8-11, and 13 were isolated from this genus for the first time, and compounds 6, 7, and 12 were obtained from H. scandens for the first time. The activity test showed that compounds 1 and 10 had a certain inhibitory effect on Mycobacterium smegmatis, with MIC_(50) values of 58.5 and 33.3 μg·mL~(-1), respectively.

Differentially expressed long noncoding RNAs and mRNAs in PC12 cells under lysophosphatidylcholine stimulation.

Lysophosphatidylcholine (LPC) was previously found to show neuroprotective effect on nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) induced signalings. Also, numerous studies reported the emerging roles of long noncoding RNAs (LncRNAs) involved in neurodegenerative disease. However, the biological mechanism of LPC and expression profile of lncRNAs has not been reported. Here, lncRNAs in PC12 cells under LPC and NGF treatment were analyzed using high throughput sequencing technology for the first time. We identified 564 annotated and 1077 novel lncRNAs in PC12 cells. Among them, 121 lncRNAs were differentially expressed in the PC12 cells under LPC stimulation. KEGG analysis showed that differentially expressed mRNAs co-expressed with lncRNAs mainly enriched in ribosome, oxidative phosphorylation, Parkinson's disease, Huntington's disease and Alzheimer's disease etc. LncRNA-mRNA network analysis showed that lncRNA ENSRNOT00000082515 had interactions with 626 different mRNAs suggesting that lncRNA ENSRNOT00000082515 probably play vital role. Finally, sequencing data were validated by qRT-PCR for ENSRNOT00000084874, ENSRNOT00000082515, LNC_001033 forward Fgf18, Vcam1, and Pck2.

Correction: Optimal designs of the side sensitive synthetic chart for the coefficient of variation based on the median run length and expected median run length.

[This corrects the article DOI: 10.1371/journal.pone.0255366.].

The trend in delayed childbearing and its potential consequences on pregnancy outcomes: a single center 9-years retrospective cohort study in Hubei, China.

BACKGROUND: Due to the advancement of modern societies, the proportion of women who delay childbearing until or beyond 30 years has dramatically increased in the last three decades and has been linked with adverse maternal-neonatal outcomes. OBJECTIVE: To determine the trend in delayed childbearing and its negative impact on pregnancy outcomes. MATERIAL AND METHODS: A tertiary hospital-based retrospective study was conducted in Wuhan University Renmin Hospital, Hubei Province, China, during the years 2011-2019. The joinpoint regression analysis was used to find a trend in the delayed childbearing and the multiple binary logistic regression model was used to estimate the association between maternal age and pregnancy outcomes. RESULTS: Between 2011 and 2019, the trend in advanced maternal age (AMA ≥35 years) increased by 75% [AAPC 7.5% (95% CI: - 10.3, 28.9)]. Based on maternal education and occupation, trend in AMA increased by 130% [AAPC 11.8% (95% CI: 1.1, 23.7)] in women of higher education level, and 112.5% [AAPC 10.1% (95% CI: 9.4, 10.9)] in women of professional services. After adjusting for confounding factors, AMA was significantly associated with increased risk of gestational hypertension (aOR 1.5; 95% CI: 1.2, 2.1), preeclampsia (aOR 1.6; 95% CI: 1.4, 1.9), sever preeclampsia (aOR 1.7; 95% CI: 1.1, 2.6), placenta previa (aOR 1.8; 95% CI: 1.5, 2.2), gestational diabetes mellitus (aOR 2.5; 95% CI: 2.3, 2.9), preterm births (aOR 1.6; 95% CI: 1.4, 1.7), perinatal mortality (aOR 1.8; 95% CI: 1.3, 2.3), and low birth weight (aOR 1.3; 95% CI: 1.2, 1.4) compared with women aged < 30 years. CONCLUSION: Our findings show a marked increase in delayed childbearing and its negative association with pregnancy outcomes.

Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study / 中国当代儿科杂志

OBJECTIVES@#To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment.@*METHODS@#A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group.@*RESULTS@#Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05).@*CONCLUSIONS@#This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

Diagnosis and treatment status of perioperative anemia in patients with gastrointestinal neoplasms: a multi-center study in Hubei Province / 中华外科杂志

Objective: To investigate the incidence and treatment of perioperative anemia in patients with gastrointestinal neoplasms in Hubei Province. Methods: The clinicopathological data of 7 474 patients with gastrointestinal neoplasms in 62 hospitals in 15 cities (state) of Hubei Province in 2019 were collected in the form of network database. There were 4 749 males and 2 725 females. The median age of the patients was 62 years (range: 17 to 96 years). The hemoglobin value of the first time in hospital and the first day after operation was used as the criterion of preoperative anemia and postoperative anemia. Anemia was defined as male hemoglobin <120 g/L and female hemoglobin <110.0 g/L, mild anemia as 90 to normal, moderate anemia as 60 to <90 g/L, severe anemia as <60 g/L. The t test and χ2 test were used for inter-group comparison. Results: The overall incidence of preoperative anemia was 38.60%(2 885/7 474), and the incidences of mild anemia, moderate anemia and severe anemia were 25.09%(1 875/7 474), 11.37%(850/7 474) and 2.14%(160/7 474), respectively. The overall incidence of postoperative anemia was 61.40%(4 589/7 474). The incidence of mild anemia, moderate anemia and severe anemia were 48.73%(3 642/7 474), 12.20%(912/7 474) and 0.47%(35/7 474), respectively. The proportion of preoperative anemia patients receiving treatment was 26.86% (775/2 885), and the proportion of postoperative anemia patients receiving treatment was 14.93% (685/4 589). The proportions of preoperative anemia patients in grade ⅢA, grade ⅢB, and grade ⅡA hospitals receiving treatment were 26.12% (649/2 485), 32.32% (85/263), and 29.93% (41/137), and the proportions of postoperative anemia patients receiving treatment were 14.61% (592/4 052), 22.05% (73/331), and 9.71% (20/206). The proportion of intraoperative blood transfusion (16.74% (483/2 885) vs. 3.05% (140/4 589), χ²=434.555, P<0.01) and the incidence of postoperative complications (17.78% (513/2 885) vs. 14.08% (646/4 589), χ²=18.553, P<0.01) in the preoperative anemia group were higher than those in the non-anemia group, and the postoperative hospital stay in the preoperative anemia group was longer than that in the non-anemia group ((14.1±7.3) days vs. (13.3±6.2) days, t=5.202, P<0.01). Conclusions: The incidence of perioperative anemia in patients with gastrointestinal neoplasms is high. Preoperative anemia can increase the demand for intraoperative blood transfusion and affect the short-term prognosis of patients. At present, the concept of standardized treatment of perioperative anemia among gastrointestinal surgeons in Hubei Province needs to be improved.

A new polyketide of endophytic fungi Aspergillus sp. ZJ-58 from Coptis chinensis / 中国中药杂志

A new polyketide, coptaspin A(1), along with two known compounds 4-acetyl-3,4-dihydro-6,8-dihydroxy-3-methoxy-5-methylisocoumarin(2), and cytochalasin Z_(12)(3), was isolated from the endophytic fungi Aspergillus sp. ZJ-58, which was isolated from the genuine medicinal plant Coptis chinensis in Chongqing after solid-state fermentation on rice and silica gel, MCI, and HPLC-based separation. Their structures were elucidated by MS, NMR, IR, UV, and ECD. The newly isolated compound 1 showed moderate inhibitory activities against LPS-induced NO production in RAW264.7 macrophages with the IC_(50) value of 58.7 μmol·L~(-1), suggesting its potential anti-inflammatory activity.

A new phloroglucinol from Dryopteris fragrans and its antibacterial activity in vitro / 中国中药杂志

A new phloroglucinol was isolated from 50% ethanol extract of Dryopteris fragrans by silica gel column chromatography, Sephadex LH-20 gel column chromatography, thin-layer chromatography(TLC), and preparative liquid column chromatography. On the basis of MS, ~1H-NMR, ~(13)C-NMR, and reference materials, compound 1 was identified as 2,5-cyclohexadien-1-one, 2-{[2,6-dihydroxy-4-methoxy-3-methyl-5-(1-isobutyl)phenyl]methyl}-3,5-dihydroxy-4,4-dimethyl-6-(1-oxobutyl)(1), and named disaspidin BB. Compound 1 was evaluated for its antibacterial activity. The experimental results showed that compared with the commonly used topical antibiotics erythromycin or mupirocin, disaspidin BB exhibited significant antibacterial activities against Staphylococcus epidermidis(SEP), S. haemolyticus(SHA), and methicillin-resistant S. aureus(MRSA)(P<0.05). Additionally, disaspidin BB was sensitive to ceftazidime-resistant SEP1-SEP4, SHA5-SHA7, MRSA8, and MRSA9. The MIC values of disaspidin BB against SEP and SHA were 1.67-2.71 μg·mL~(-1) and 10.00-33.33 μg·mL~(-1) respectively. Disaspidin BB has good antibacterial activities and deserves development as a new anti-infective drug for external use.

Secondary metabolites of endophyte fungi Xylaria sp. from Coptis chinensis / 中国中药杂志

Two new polyketides, lasobutone A(1) and lasobutone B(2), along with three known compounds, guignardianone C(3), guignardic acid(4), and 4-hydroxy-17R-methylincisterol(5), were isolated from the endophytic fungi Xylaria sp. by silica gel, MCI, and preparative HPLC, which was separated from the Chinese medicinal material Coptis chinensis and cultivated through solid fermentation with rice. Their structures were elucidated on the basis of spectroscopic methods, such as MS, NMR, IR, UV, and ECD. Compounds 2 and 4 showed inhibitory activities against the nitric oxide(NO) production in the LPS-induced macrophage RAW264.7 with IC_(50) values of 58.7 and 42.5 μmol·L~(-1) respectively, while compound 5 exhibited cytotoxic activities against HT-29 with IC_(50) value of 14.3 μmol·L~(-1).

Optimal designs of the side sensitive synthetic chart for the coefficient of variation based on the median run length and expected median run length.

The side sensitive synthetic chart was proposed to improve the performance of the synthetic chart to monitor shifts in the coefficient of variation (γ), by incorporating the side sensitivity feature where successive non-conforming samples must fall on the same side of the control limits. The existing side sensitive synthetic- γ chart is only evaluated in terms of the average run length (ARL) and expected average run length (EARL). However, the run length distribution is skewed to the right, hence the actual performance of the chart may be frequently different from what is shown by the ARL and EARL. This paper evaluates the entire run length distribution by studying the percentiles of the run length distribution. It is shown that false alarms frequently happen much earlier than the in-control ARL (ARL0), and small shifts are often detected earlier compared to the ARL1. Subsequently, this paper proposes an alternative design based on the median run length (MRL) and expected median run length (EMRL). The optimal design based on the MRL shows smaller out-of-control MRL (MRL1), which shows a quicker detection of the out-of-control condition, compared to the existing design, while the results from the optimal design based on the EMRL is similar to that of the existing designs. Comparisons with the synthetic-γ chart without side sensitivity shows that side sensitivity reduces the median number of samples required to detect a shift and reduces the variability in the run length. Finally, the proposed designs are implemented on an actual industrial example.

Intrinsic and chemically-induced daughter number variations in cancer cell lines.

Multipolar mitosis was observed in cancer cells under mechanical stress or drug treatment. However, a comprehensive understanding of its basic properties and significance to cancer cell biology is lacking. In the present study, live-cell imaging was employed to investigate the division and nucleation patterns in four different cell lines. Multi-daughter divisions were observed in the three cancer cell lines HepG2, HeLa and A549, but not in the transformed non-cancer cell line RPE1. Multi-daughter mother cells displayed multi-nucleation, enlarged cell area, and prolonged division time. Under acidic pH or treatment with the anti-cancer drug 5-fluorouracil (5-FU) or the phytochemical compound wogonin, multi-daughter mitoses were increased to different extents in all three cancer cell lines, reaching as high as 16% of all mitoses. While less than 0.4% of the bi-daughter mitosis were followed by cell fusion events under the various treatment conditions, 50% or more of the multi-daughter mitoses were followed by fusion events at neutral, acidic or alkaline pH. These findings revealed a "Daughter Number Variation" (DNV) process in the cancer cells, with multi-daughter divisions in Stage 1 and cell fusions leading to the formation of cells containing up to five nuclei in Stage 2. The Stage 2-fusions were inhibited by 5-FU in A549 and HeLa, and by wogonin in A549, HeLa and HepG2. The parallel relationship between DNV frequency and malignancy among the different cell lines suggests that the inclusion of anti-fusion agents exemplified by wogonin and 5-FU could be beneficial in combinatory cancer chemotherapies.

The Heterogeneous Effects of Participation in Shadow Education on Mental Health of High School Students in Taiwan.

The effect of shadow education or private supplementary education (PSE) on school achievement has been prolifically studied, but its impact on well-being remains understudied. This study examines the heterogeneous effect of PSE participation on school achievement and depression symptoms among high schoolers in Taiwan. The study uses panel data of the Taiwan Upper Secondary Database (TUSD) in the 2014 and 2015 academic years. We join the inverse-probability-of-treatment weighting (IPTW) approach and the seemingly unrelated regression (SUR) model to estimate the effects of PSE participation patterns on two correlated outcomes, comprehensive assessment of high school entrance examination and self-reported depression symptoms in the 11th grade. The latent class analysis identifies five PSE participation patterns: always-taker, early-adopter, dropout, late-adopter, and explorer, to predict the effect of PSE on the scores of entrance examination and later depression symptoms in high school (n = 7708, mean age = 15.33). The findings suggest that PSE participation in junior high is positively associated with academic achievement. However, PSE participation also increases depression symptoms, particularly in the case of always-takers. In other words, while always-takers increase their school achievement in transition into high school, their risks of suffering from depression are also higher than their peers.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial / 中西医结合学报

BACKGROUND@#Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.@*OBJECTIVE@#This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m@*MAIN OUTCOME MEASURES@#The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.@*RESULTS@#A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.@*CONCLUSION@#SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.@*TRIAL REGISTRATION NUMBER@#NCT02063100 on ClinicalTrials.gov.

Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial

BackgroundNo clinically proven effective antiviral strategy exists for the epidemic Coronavirus Disease 2019 (COVID-19). MethodsWe conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Patients were randomly assigned in a 1:1 ratio to receive conventional therapy plus Umifenovir (Arbidol) (200mg*3/day) or Favipiravir (1600mg*2/first day followed by 600mg*2/day) for 10 days. The primary outcome was clinical recovery rate of Day 7. Latency to relief for pyrexia and cough, the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV) were the secondary outcomes. Safety data were collected for 17 days. Results240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive Favipiravir (116 assessed), and 120 to receive Arbidol (120 assessed). Clinical recovery rate of Day 7 does not significantly differ between Favipiravir group (71/116) and Arbidol group (62/120) (P=0.1396, difference of recovery rate: 0.0954; 95% CI: -0.0305 to 0.2213). Favipiravir led to shorter latencies to relief for both pyrexia (difference: 1.70 days, P<0.0001) and cough (difference: 1.75 days, P<0.0001). No difference was observed of AOT or NMV rate (both P>0.05). The most frequently observed Favipiravir-associated adverse event was raised serum uric acid (16/116, OR: 5.52, P=0.0014). ConclusionsAmong patients with COVID-19, Favipiravir, compared to Arbidol, did not significantly improve the clinically recovery rate at Day 7. Favipiravir significantly improved the latency to relief for pyrexia and cough. Adverse effects caused Favipiravir are mild and manageable. This trial is registered with Chictr.org.cn (ChiCTR2000030254).