Objective:To investigate the clinical characteristics of family clustering pediatric and adult cases with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection in Shanghai City.Methods:A field investigation among the pediatric cases with Omicron variant infection and their household contacts from April 4 to April 30, 2022 in Children′s Hospital of Fudan University was conducted. The informations on case finding, clinical manifestations and SARS-CoV-2 vaccination status were collected. The epidemiological and clinical characteristics were compared between pediatric cases and adult cases. The independent sample t test or chi-square test was used for statistical analysis, and the relative risk ( RR) and 95% confidence interval (95% CI) were used to evaluate the protective effect of vaccination on the infection of Omicron variant. Results:There were 1 274 family members in 297 families including 370 children and 904 adults of whom 1 110(87.13%) were infected with Omicron variant, with 989(89.10%) symptomatic and 121(10.90%) asymptomatic. There were 355 children infected with Omicron variant, of whom 337(94.93%) were symptomatic, and the main manifestations were fever (96.74%(326/337)) and cough (40.36%(136/337)). Only one pediatric case with Rett syndrome developed critically severe pneumonia. A total of 194 pediatric cases had imaging examination, 64(32.99%) showed pulmonary inflammatory lesions. There were 755 adult cases infected with Omicron variant, of whom 652(86.26%) reported symptoms, and the main manifestations were fever (73.16%(477/652)) and cough (49.85%(325/652)). Among symptomatic cases, fever was more common in pediatric cases than in adult cases, while cough was more common in adult cases than in pediatric cases, and the differences were both statistically significant ( χ2=80.87 and 8.04, respectively, both P<0.01). The fever spike was higher in pediatric cases than in adult cases ((39.3±0.7) ℃ vs (38.6±0.6) ℃), and the difference was statistically significant ( t=9.85, P<0.001). The interval from the onset of symptoms to cycle threshold (Ct) value of the nucleic acid of Omicron variant≥35 was longer in pediatric cases than in adult cases ((13.0±3.1) d vs (10.9±3.6) d), and the difference had statistically significance ( t=2.97, P=0.004). Among 160 children aged 3 to 18 years, 54 (33.75%) received two-dose vaccination. Among the 904 adults, 388 (42.92%) received two-dose vaccination and 293 (32.41%) received a booster dose. In the adult cases, the risk of symptomatic infection was reduced by only 8% ( RR=0.92, 95% CI 0.86 to 0.98, P=0.014) following two-dose vaccination, and the risks of fever and cough following booster vaccination were reduced by 42%( RR=0.58, 95% CI 0.49 to 0.67, P=0.001) and 50% ( RR=0.50, 95% CI 0.34 to 0.78, P=0.001), respectively. Conclusions:Secondary attack rate and symptomatic rate of household infection are high in the context of the Omicron variant outbreak in Shanghai. Symptomatic infection is common in children and adults in household setting. Fever is the most common symptom and fever duration is short. Booster vaccination may provide certain protection against common symptoms caused by Omicron variant infection.

Objective To explore the temporal and spatial distribution characteristics of air pollutants PM_2.5, PM₁₀, SO₂, CO, and NO₂, and their effects on acute cerebrovascular diseases in Jining City. Methods The data of patients with acute cerebrovascular disease treated in a 3A hospital in Jining from October 1, 2017, to November 31, 2019, were retrospectively collected. Combined with the air pollution data of 29 air quality monitoring stations in Jining City, the Kriging interpolation model was used to analyze the overall situation of air pollution in Jining. On this basis, the relationship between air pollution and acute cerebrovascular diseases in Jining City was analyzed. Results In Jining City, the incidence of acute cerebrovascular disease in male was higher than that in female, and the incidence in rural areas was significantly higher than that in urban areas. The spatial distribution showed a trend of gradual accumulation from southeast to northwest. The daily average concentrations of PM2.5 and PM10 were higher in winter and spring than in summer and autumn. The results of Kriging interpolation analysis showed that the concentrations of these air pollutants formed aggregation points in varying degrees. The spatial distribution of acute cerebrovascular disease patients in Jining City was highly consistent with the spatial distribution of air pollutant concentrations. Spearman correlation analysis showed that CO, SO₂, and NO₂ were positively correlated with the incidence of acute cerebrovascular disease, while the correlation between PM_2.5 and PM₁₀ and the incidence of acute cerebrovascular disease was not significant. Conclusion Some air pollutants such as CO, SO₂, and NO₂ have a positive correlation with the incidence of acute cerebrovascular disease, and the prevalence has a certain population and regional distribution. In the future work of cerebrovascular disease prevention, personal protection should be done according to local conditions and living environment of specific people.

Objective: To investigate the expression profile and function of FANCF gene (a key gene in FA/BRCA pathway) in both cisplatin (DDP)-resistant and DDP-sensitive human triple-negative breast cancer cell lines and to analyze its correlation with DDP-resistance in breast cancer. Methods: The DDP-resistant breast cancer MDA-MB-231 cell line (MDA-MB-231/DDP) was established by induction of gradient DDP. The expression of FANCF gene in both sensitive and resistant cell lines was knocked-down by RNAi interference technology and the knockdown efficiency was validated at both RNA and protein level. The cell viability of MDA-MB-231 cells and MDA-MB-231/DDP cells was determined by the CCK8 assay; Flow cytometry was used to examine the cell cycle distribution and apoptosis; the mRNAand protein expressions of FANCF gene were examined by using qRT-PCR and western blotting, respectively. Results: The resistance index of MDA-MB-231/DDP cells was 13.5 after 3-month induction. The mRNA and protein expressions of FANCF were significantly increased in MDA-MB-231/DDP cells (all P<0.01). Cell cycle analysis indicated that the DDP treatment significantly induced G0/G1 arrest and decreased the cell proportion in phase S and G2/M. siRNA-mediated knockdown of FANCF could not only be able to increase sensitivity of MDA-MB-231 to DDP but also promote the cell apoptosis (all P<0.01). Conclusion: FANCF attributes to the occurrence of DDP-resistance through anti-apoptosis effect, which might be served as a potential treatment target for drug-resistant human breast cancer.

Objective To investigate the effects of propofol on mesenteric artery in SD rats and to observe whether the effect of propofol on the mesenteric artery relaxation is related to the gap. Methods Pressure myograph was used to examine the effect of 18β-GA and 2-APB on the relaxation induced by propofol 1×10 -7 ,3×10 -7 ,1×10 -6 ,3×10 -6 ,1 ×10 -5 ,3 ×10 -5 ,1 ×10 -4 and 3 ×10 -4 mol/L in acutely separated mesenteric arterioles of SD rat.Results The diameter of mesenteric arteri-oles were increased from (208.6±13.4)to (213.5±13.6),(21 9.7±13.2),(226.4±12.5),(234.9 ±12.3),(245.5±13.0),(267.4±1 5.2),(336.2±18.3)and (385.9 ±14.2)μm after application of 1×10 -7 ,3×10 -7 ,1 × 10 -6 ,3 × 10 -6 ,1 × 10 -5 ,3 × 10 -5 ,1 × 10 -4 and 3 × 10 -4 mol/L propofol,re-spectively.Propofol induced dilation of the rat mesenteric arterioles in a concentration-dependent man-ner (P < 0.01 ).After pretreatment with 18β-GA and 2-APB,1 × 10 -4 mol/L propofol induced dilation was absolutely decreased (P <0.01).Conclusion These results suggest that propofol relaxes mesenteric arterioles via gap junction.

BACKGROUNDPrediabetes is an early stage of β-cell dysfunction presenting as insulin resistance. Evidences suggest that endoplasmic reticulum (ER) stress is involved in the pathogenesis of type 2 diabetes mellitus and prediabetes. In a Chinese population with prediabetes, we investigated single nucleotide polymorphisms (SNPs) in the genes of PERK, JNK, XBP1, BIP and CHOP which encode molecular proteins involved in ER stress pathways.

METHODSNine SNPs at the PERK, JNK, XBP1, BIP and CHOP loci were genotyped by mass spectrometry in 1 448 unrelated individuals. By using a 75 g oral glucose tolerance test (OGTT), 828 subjects were diagnosed as prediabetes and 620 subjects aged 55 years and over as normal controls based on WHO diagnostic criteria (1999) for diabetes mellitus.

RESULTSThe allele C of SNP rs867529 at PERK locus was a risk factor for prediabetes, with the carriers of C allele genotype at a higher risk of prediabetes compared to non-carriers (OR = 1.279, 95% CI: 1.013-1.614, P = 0.039, after adjustment for age, sex and body mass index (BMI). The SNPs rs6750998 at PERK locus was associated with homeostasis model assessments of insulin resistance (HOMA-IR) (P = 0.019), and rs17037621 with BMI (P = 0.044). The allele G of SNP rs10986663 in BIP gene was associated with a decreased risk of prediabetes (OR = 0.699, 95% CI: 0.539-0.907, P = 0.007). The SNP rs2076431 in JNK gene was associated with fasting plasma glucose levels (P = 0.006) and waist-hip ratios (P = 0.019). The SNP rs2239815 in XBP1 gene was associated with 2-hour plasma glucose levels after 75 g oral glucose load (P = 0.048) in the observed population.

CONCLUSIONCommon variants at PERK and BIP loci contributed to the risk of prediabetes, and the genetic variations in JNK and XBP1 genes are associated with diabetes-related clinical parameters in this Chinese population.

Aged ; DNA-Binding Proteins ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Genotype ; Humans ; MAP Kinase Kinase 4 ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Prediabetic State ; genetics ; Regulatory Factor X Transcription Factors ; Transcription Factor CHOP ; genetics ; Transcription Factors ; genetics ; X-Box Binding Protein 1 ; eIF-2 Kinase ; genetics

OBJECTIVETo evaluate the prognosis of cervical intraepithelial neoplasia grade 1 (CIN1) at different follow-up time points in Chinese women and the relationship with high-risk human papillomavirus (HR-HPV) infection.

METHODSBiopsy-confirmed CIN1 women were followed up from cervical cancer screening cohorts established during 1999 to 2008 in Xiangyuan county, Yangcheng county, Qinxian county and Wuxiang county, Shanxi Province.In each follow-up visit, participants were examined by visual inspection with acetic acid, liquid-based cytology and HR-HPV DNA testing. Those with any positive results received colposcope and biopsies. The cumulative incidence rates of CIN grade 2 or worse (CIN2+) and CIN grade 3 or worse (CIN3+), regression rates and persistent rates were calculated using pathological findings as a gold standard. The risks of progression related with HR-HPV were evaluated stratified by baseline and follow-up HR-HPV status.

RESULTSA total of 228, 224, 261 and 105 CIN1 women received the 1-year, 2-year, 6-year and 11-year follow-up exams, respectively. The cumulative incidence rate of CIN2+ among baseline HR-HPV positive women was 4.8% (6/126), 10.7% (16/150), 16.9% (29/172) and 35% (19/55) in the above follow-up visits, respectively, and their risk of progression was 2.7(95%CI:0.3-22.0), 2.9 (95%CI:0.7-12.1), 12.0 (95%CI:1.7-86.2) and 30.6 (95%CI:1.9-493.5) times higher than baseline HR-HPV negative women. Moreover, the cumulative incidence of CIN2+ among women with positive HR-HPV both at baseline and follow-up visit was 11% (6/55), 14% (6/42), 17% (10/60) and 50% (13/26) in the above follow-up visits, respectively.No new CIN2+ cases were found among those with negative HR-HPV both at baseline and follow-up visits.

CONCLUSIONGiven that CIN1 progression is related to HR-HPV infection, different follow-up intervals and strategies for CIN1 should be taken according to HR-HPV infection status.

Aged ; Biopsy ; Cervical Intraepithelial Neoplasia ; Disease Progression ; Female ; Humans ; Papillomavirus Infections ; Prognosis ; Prospective Studies ; Uterine Cervical Neoplasms

Objective To investigate the impact of multi-drug transporters including P-glycoprotein (PGP) and multi-drug resistance associated protein (MRP) on concentration of lamotrigine in the extracellular fluid in hippocampus of epilepsy rat models induced by pilocarpine, and to deduce the multi-drug resistance mechanisms in refractory epilepsy. Methods The epilepsy rat models were established by repeated administration (by ip) of pilocarpine. A microdialysis probe was placed into the hippocampus of the epileptic rats and dialysate was collected at five time-points from 30--150 minutes after systemic injections of lamotrigine (10 mg/kg). The concentration of lamotrigine in the extracellular fluid in the hippocampus was determined by high-performance liquid chromatography (HPLC). Then PGP inhibitor verapamil and MRP inhibitor probenecid was added individually through microdialysis probe and the concentration of lamotrigine was detected again. Results Compared with control group (0. 41 ± 0. 10 in 60 minutes, 0. 50 ±0.04 in 90 minutes, 0. 39 ±0. 09 in 120 minutes and 0. 30±0.06 in 150 minutes), verapamil significantly increased the concentration of lamotrigine in extracellular fluid of the hippocampus 60--150 minutes (0. 65 ±0. 11, 0. 84 ± 0. 09, 0. 70± 0. 09 and 0. 58 ± 0. 08 respectively) after injection (F value were 5.01, 8.61, 10. 23 and 7.89, all P < 0. 05) and probenecid also enhanced the concentration of lamotrigine 90--150 minutes (0. 75 ± 0. 09, 0. 58±0. 10 and 0. 49±0. 07) after injection (F = 6. 58, 4. 56, 4. 75, all P < 0. 05). Conclusions Penetration of lamotrigine through blood-brain barrier in pilocarpine induced epilepsy rats is restricted by PGP and MRP, resulting in decreased concentration of lamotrigine in the extracellular fluid of the hippocampus. Therefore, increasing expression of PGP and MRP in brains of epilepsy patients might be an important mechanism involved in multi-drug resistance in refractory epilepsy.

Objective To study the effect of inhibitors of the multidrug transporters including P-glycoprotein (PGP)and multi-drug resistance-associated protein(MRP)on the regulation of concentration of oxcarbazepine in the extra-cellular fluid of the hippocampus after pilocarpine induced seizures in rats.To investigate whether oxcarbazepine are sub-strate for PGP and MRP and whether brain expressions of PGP and MRP are involved in muhidrug resistance mechanisms of refractory epilepsy.Methods The epileptic rats model were established by repeated peritoneal injection treatment with pi-locarpine.Thirty-two Wistar rats were divided into four groups:control group,pilocarpine epileptic model group,verapamil treated group and probenecid treated group.At 30,60,90,120 and 150 min following systemic injection of oxcarbazepine (80 mg/kg),dialysate was collected and the concentration of oxcarbazepine in the extracellular fluid of hippocampus was determined by microdialysis and high-performance liquid chromatography technique.Results After systemic injection of oxcarbazepine,the concentration of oxcarbazepine in extracellular fluid of the hippocampus during 90～150 min(1.26±0.09、0.93±0.10)were much higher in verapamil treated group than in pilocarpine epileptic model group(0.87±0.06、0.66±O.04)(P<0.05)and the concentration of oxcarbazepine in the hippocampus during 60～150 min(1.07 4±0.11、1.32±O.13、1.02±0.10、0.87±0.08)were higher in probenecid treated group than in pilocarpine epileptic model group (0.81±0.08、0.87±0.06、0.66.4±0.04、0.58±0.06)(P<0.05).Conclusions Oxcarbazepine are substrates for PGP and MRP and,penetration of oxcarbazepine through blood-brain barrier are restricted by PGP and MRP.Increased expres-sions of PGP and MRP in brain maybe involved in the mechanisms of multidrug resistance of refractory epilepsy.

Objective Identify the arsenic and fluorin contents in coal from major producing coal mines in south of Shaanxi,providing a scientific foundation for the formulation of the prevention strategy.Methods In the 6 major coal mine areas governed by Ankang and Hanzhong city,the 62 mines with comparatively large production scales and sales locally,which may have some effective forces on the causing of the local arsenic and fluorin poisoning,were inveatigated,on-the-spot sampling are carried out,the fluorine in coal was determined by the combustion-hydrolysis/fluoride-ion selective electrode method and the arsenic in coal was determined by the atomic fluorescence.Results The maximum of the fluoride content in coal from the 62 investigated coal mines was 3 053.04 mg/kg,and the minimum was 6.58 mg/kg;the arithmetic mean was 1 034.30 mg/kg;the geometric mean was 656.85 mg/kg;The maximum of arsenic content in coal was 484.71mg/kg,and the minimum was 29.64 mg/kg;the arithmetic mean was 197.64 mg/kg,the geometric mean was 174.29 mg/kg.Conclusion The contents of fluoride and arsenic are seriously exceeded the standard limits in the 62 investigated coal mines,especially in stone coal mines.

Objective To study the effect of P-glycoprotein (PGP) in regulation of penetration of carbamazepine and phenytoin through blood-brain barrier, as to indicating the entry of epileptic drugs into the brain restricted by PGP and deducing the multidrug resistance mechanisms of refractory epilepsy. Methods The microdialysis probe was placed into the cortex of rats, and after systemic injection of carbamazepine and phenytoin, dialysate was collected and the antiepiletic drug concentration in the extracellular fluid of the cerebral cortex was determined by high-performance liquid chromatography (HPLC). Then observing whether the concentration of drugs in extracellular fluid can be enhanced by PGP’s inhibitor verapamil. Results Verapamil significantly enhanced the concentration of carbamazepine in extracellular fluid of the cerebral cortex during 60—90 minutes after injection ((1.74?0.28)?g/ml in 60 minutes and (1.87?0.31)?g/ml in 90 minutes,P