Humans ; Esophageal Squamous Cell Carcinoma ; Esophageal Neoplasms/pathology* ; Carcinoma, Squamous Cell ; Microbiota

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Objective: Traditional uterine manipulator is considered as the main reason for short survival of patients with early-stage cervical cancer during minimally invasive surgery. This study aims to assess the sealing effect of magnetic-sealing uterine manipulators (MUMs) in isolated uteruses. Methods: The study was performed on isolated uterus from patients with early-stage cervical cancer who underwent open abdominal radical hysterectomy between November 2019 to April 2021. Right-angle forceps closure tests (groups 1 and 3) were defined as control tests. One experimental MUM closure test (group 2) and 2 control tests were respectively carried out in each of the isolated uterus. DNA ploidy analysis system was used to observe exfoliated cells. Statistical analysis was performed using Wilcoxon signed-rank test to assess the sealing effect of MUM. Results: We identified 36 patients. No regional node metastasis was discovered and only one tumor was larger than 4.0 cm in diameter. The mean of exfoliated tumor cells in groups 1, 2, and 3 were 1, 1, and 2, respectively. There was no significant difference in the quantity of exfoliated cells between groups 1 and 3 (p=0.476), so the results of the 2 groups were merged. Subsequently, a significant difference was observed between combined right-angle forceps closure tests and MUM closure tests (p=0.022). Conclusion The sealing effect of MUM was better than that of right-angle forceps. MUM can effectively seal cervical cancer cells in the cup cover, avoiding the dissemination of tumor cells.

Gut microbiome sequencing studies have great potential to translate microbial analysis outcomes into human health research. Sequencing strategies of 16S amplicon and whole-metagenome shotgun (WMS) are two main methods in microbiome research with respective advantages. However, how sample heterogeneity, sequencers and library preparation protocols affect the sequencing reproducibility of gut microbiome needs further investigation. This study aims to provide a reference for the selection of sequencing technologies by comparing differences in microbial composition from different sampling sites. The results of three widely adopted sequencers showed that the technical repetition correlation (r= 0. 94) was high in WMS method, while the biological repetition correlation (r = 0. 69) was low. Bray-Curtis distance identified that dissimilarity from biological replicates was larger than that of technical replicates (P<0. 001). In addition, dissimilarity and specific taxonomic profiles were observed between 16S and WMS datasets. Our results imply that homogenization is a necessary step before sample DNA extraction. The sequencers contributed less to taxonomic variation than the library preparation protocols. We developed an empirical Bayes approach that " borrowed information" in calculations and analyzed batch effect parameters using standardized data and prior distributions of (non-) parameters, which may improve population comparability between 16S and WMS and provide a basis for further application to fusion analysis of published 16S and microbial datasets.

Objective: To determine the spatiotemporal distribution of Schistosoma (S.) japonicum infections in humans, livestock, and Oncomelania (O.) hupensis across the endemic foci of China. Methods: Based on multi-stage continuous downscaling of sentinel monitoring, county-based schistosomiasis surveillance data were captured from the national schistosomiasis surveillance sites of China from 2005 to 2019. The data included S. japonicum infections in humans, livestock, and O. hupensis. The spatiotemporal trends for schistosomiasis were detected using a Joinpoint regression model, with a standard deviational ellipse (SDE) tool, which determined the central tendency and dispersion in the spatial distribution of schistosomiasis. Further, more spatiotemporal clusters of S. japonicum infections in humans, livestock, and O. hupensis were evaluated by the Poisson model. Results: The prevalence of S. japonicum human infections decreased from 2.06% to zero based on data of the national schistosomiasis surveillance sites of China from 2005 to 2019, with a reduction from 9.42% to zero for the prevalence of S. japonicum infections in livestock, and from 0.26% to zero for the prevalence of S. japonicum infections in O. hupensis. Analysis using an SDE tool showed that schistosomiasis-affected regions were reduced yearly from 2005 to 2014 in the endemic provinces of Hunan, Hubei, Jiangxi, and Anhui, as well as in the Poyang and Dongting Lake regions. Poisson model revealed 11 clusters of S. japonicum human infections, six clusters of S. japonicum infections in livestock, and nine clusters of S. japonicum infections in O. hupensis. The clusters of human infection were highly consistent with clusters of S. japonicum infections in livestock and O. hupensis. They were in the 5 provinces of Hunan, Hubei, Jiangxi, Anhui, and Jiangsu, as well as along the middle and lower reaches of the Yangtze River. Humans, livestock, and O. hupensis infections with S. japonicum were mainly concentrated in the north of the Hunan Province, south of the Hubei Province, north of the Jiangxi Province, and southwestern portion of Anhui Province. In the 2 mountainous provinces of Sichuan and Yunnan, human, livestock, and O. hupensis infections with S. japonicum were mainly concentrated in the northwestern portion of the Yunnan Province, the Daliangshan area in the south of Sichuan Province, and the hilly regions in the middle of Sichuan Province. Conclusions: A remarkable decline in the disease prevalence of S. japonicum infection was observed in endemic schistosomiasis in China between 2005 and 2019. However, there remains a long-term risk of transmission in local areas, with the highest-risk areas primarily in Poyang Lake and Dongting Lake regions, requiring to focus on vigilance against the rebound of the epidemic. Development of high-sensitivity detection methods and integrating the transmission links such as human and livestock infection, wild animal infection, and O. hupensis into the surveillance-response system will ensure the elimination of schistosomiasis in China by 2030.

Objective: To investigate the current situation of drug supply and determinants of drug shortage in primary health institutions in Anhui province. Methods:Primary health institutions in Anhui province were selected as the main research subjects. One hundred and six (106) primary health institutions from three areas/districts in Anhui province namely northern Anhui,Central Anhui,and Southern Anhui were selected with stratified random sampling as the first sample,and 54 pharmaceutical producing enterprises and 62 pharmaceutical trading enterprises were selected with convenience sampling method as the second sample. The survey was conducted by issuing questionnaires to record views of the respondents to help understand the current situation of drug supply from the first sample and the main de-terminants and solutions of drug shortage from two samples. Results:13% of the primary health institutions still suffer from serious shortage of drug supply; the drug distribution rate varies greatly between units, and 19% of the primary health institutions have a drug distribution rate below 70%,and all primary health institution within the scope of inves-tigation experienced drug shortages. The frequency of choices of determinants of drug shortage were in sequence of or-der:drug demand instability (19.20%), drugs have a new and higher profit alternative (15.94%), etc.; The fre-quency of choices of solutions of drug shortage of primary health institution were in sequence of order:to improve the national list of essential medicines(12.78%),appropriate improvement in efficacy the low-priced varieties(with cura-tive effect) (12.03%),etc. Conclusions:Primary health institutions suffer from drug shortage issue widely,and the reasons for the shortage of drugs are more complicated;the government should continue to implement relevant policies, comprehensively improving the primary health institution drug supply mechanisms in all to prevent drug shortages.

Objective To verify the performance characteristics of the human SLCO1B1 & APOE gene detection kit (PCR-fluorescent probe technique).Methods The verification protocol for the human SLCO1B1 & APOE gene detection kit manufactured by Wuhan YZY Medical Science and Technology Co.,Ltd.was designed by referring to the requirements of professional standard and pertinent literatures,and its accuracy,specificity,lowest detection limit and anti-interference ability were compared with those of sequencing technique (gold standard).Results The results coincidence of 20 clinical samples from fluorescence PCR and sequencing technique was 100％,which met the requirement of accuracy.Forty clinical samples with wild type loci determined by fluorescence PCR were verified by sequencing and no any mutation was detected,which met the requirement of specificity.The lowest detection limit of the kit was 10 ng/μL.Three interfering substances,including hemoglobin,bilirubin and triglyceride,were individually added into the blood samples with known genotype,and the results determined by the kit were coincident with that without interfering substances,which met the requirement of anti-interference ability.Conclusion The verification parameters of the human SLCO1B1 & APOE gene detection kit are basically consistent with the manufacturer's statement,indicating that the kit meets the requirements of the relevant quality management and may be applied to the detection of clinical samples.

Objective To determine the trend of emergency department (ED)mortality of a tertiary general hospital from 2004 to 2014 in order to find the factors that may impact on ED mortality.Methods Mortality in ED was estimated according to the ratio of ED visiting patients to ED deaths.And the data of all ED deaths in 2004,2009 and 2014 were collected.Variance analysis and chi-square test were used for data analysis.Results During the past decade,ED visiting patients was increased significantly by 38.0% in 2014,compared with those in 2004,and the mortality was also increased accordingly from 0.7% in 2004, to 0.9% in 2009,to 1.2% in 2014 (P <0.01).Finally,a total of 1,091 deaths occurred in these three years were included for further evaluation.There were no significant changes in average age and gender distribution,and the average age was 61.9 and the male /female ratio was 1.36∶1 during past decade.The number of adults under 40 years old (18 -39)increased from 7.5% in 2004,to 10.6% in 2009,to 14.4% in 2014 (P <0.05).Both the facilities were upgraded and the number of staffs in ED increased markedly.The cardiovascular illness,cerebrovascular diseases,and sudden death were the leading causes of ED death during past decade.The incidences of trauma and tumor remained unchanged.Average time consumed from onset of illness to arrival to ED didn’t vary significantly during past decade.The study showed no changes in use of ambulance,but remarkable increases in number of non-compliant patients or their family from 18.3% in 2004,to 25.6% in 2009,to 38.3% in 2014 (P <0.01).The percentage of patients in the night time was higher,but there were no significant changes in number of emergency patients in the night time and during holidays in the past decade,but the mean ED stay time increased obviously from 22.4 h in 2004 to 53.3 h in 2014 (P <0.05 ).Conclusions During the past decade,although ED facilities and number of staffs have been improved apparently,ED mortality rate still keeps on escalating. The increase in ED mortality rate may be related to the severely ill patients presenting to ED,the obvious decrease in compliance of patients and the prolonged ED stay time.

OBJECTIVETo investigate the effect of premature rupture of the membrane (PROM) on neonatal complications in premature infants.

METHODSThe registration information of 7684 preterm infants with gestational age <37 weeks were collected from the cooperative units in the task group between January 1, 2014 to December 31, 2014. Specially trained personnel from each cooperative units filled in the unified form in a standardized format to record the gender, gestational age, birth weight, PROM, placental abruption, antenatal corticosteroid, Apgar score, amniotic fluid pollution, and complications of the infants. The data were analyzed comparatively between the cases with PROM and those without (control).

RESULTSThe preterm mortality rate was significantly lower but the incidences of ICH, NEC, ROP and BPD were significantly higher in PROM group than in the control group (P<0.05). The 95% confidence interval of the OR value was <1 for mortality, and was >1 for ICH, NEC, ROP and BPD. After adjustment for gestational age, birth weight, gender, mode of delivery, placental abruption, placenta previa, prenatal hormones, gestational diabetes mellitus (GDM), gestational period hypertension and 5-min Apgar score <7, the incidences of NEC, ROP and BPD were significantly different between the two groups (P<0.05) with 95% confidence interval of OR value >1, but the mortality rate and incidence of ICH were not significantly different between the two groups (P>0.05).

CONCLUSIONPROM is a risk factor for NEC, ROP and BPD in preterm infants, and adequate intervention of PROM can reduce the incidences of such complications as NEC, ROP and BPD in the infants.

Apgar Score ; Birth Weight ; Female ; Fetal Membranes, Premature Rupture ; pathology ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Infant, Newborn, Diseases ; etiology ; Infant, Premature ; Pregnancy ; Risk Factors

Objective To evaluation in vitro activity and synergy of Yin-hua Miyan Ling against main clinical isolated strains.Methods All of 285 stains from 18 tertiary hospitals in recent three years were studied. Minimal inhibition concentrations ( MIC ) were tested by Agar dilution method and combination effects were measured by Checkerboard method. Results Yinhua Miyan Ling showed more in vitro activity against Sta-phylococcus and Proteus mirabilis, MIC values from 3.13~6.25 mg? mL-1 . On the other hand, Yinhua Miyan Ling showed the same antibiotic activi-ty against extended-spectrumβlactamases ( ESBLs) positive and nega-tive strains or methecillin susceptible and resistant Staphylococcus.Syner-gy was detected with Yinhua Miyan Ling in combination with amoxillin/clavulanate, cefuroxime and levofloxacin against gram-positive strains, especially methicillin-resistant Staphylococcus aureus ( MRSA).Against E.faecalis, synergy was observed in Yinhua Miyan Ling and cefuroxime. Additive effect was found between Yinhua Miyan Ling and amoxillin/clavulanate against 100%E.coli.Conclusion Synergy was found with Yinhua Miyan Ling in combination withβlactams and quinolones against gram -positive strains and additive effect was found against gram-negative bacilli.