This study was aimed at summarizing the epidemiological characteristics and spatial-temporal changes of hemorrhagic fever with renal syndrome(HFRS)in Hubei Province,China from 2005 to 2021,to provide scientific evi-dence for HFRS prevention and control.Data on individual HFRS cases and population information in Hubei Province from 2005 to 2021 were collected from the China Disease Pre-vention and Control Information System.The temporal,spa-tial,and demographic distribution characteristics of HFRS cases are described,and statistical methods such as medians,rates,and composition ratios were used for analysis.Joinpoint re-gression and Spearman's rank correlation were used to analyze the temporal trends in incidence rates or composition ratios.Global autocorrelation and hotspot analysis were conducted for spatial clustering analysis.Binary logistic regression was per-formed to analyze risk factors for HFRS mortality.A total of 5 790 HFRS cases were reported from 2005 to 2021,including 117 deaths.The average annual incidence rate was 0.57 per 100 000 population,and the case fatality rate was 2.02％.The overall incidence rate of HFRS in Hubei Province showed an increasing trend(AAPC=4.05％,95％CI:1.32％-6.78％),whereas the case fatality rate showed a decreasing trend over the years(r,=-0.72,P=0.002).HFRS exhibited a bimodal pattern,with peaks in the spring/summer months(May to July)and in the autumn/winter months(November to January of the following year).The incidence rate during the autumn/winter peak was slightly higher than that in the spring/summer peak.The incidence rate in males was higher than in females(RR=2.96,95％CI:2.79-3.14).The three age groups with the highest incidence rates were 60-64 years(747 cases,1.55 per 100 000),65-69 years(515 cases,1.39 per 100 000),and 55-59 years(762 cases,1.23 per 100 000).The incidence rate(2005:0.05 per 100 000;2021:0.08 per 100 000)and proportion(2005:2.69％;2021:1.94％)of HFRS cases in individuals 14 years or younger showed no significant trend over the years(AAPC=0.14％,95％CI:-0.03％-0.31％;AAPC=-3.64％,95％CI:-8.79％-1.50％).The incidence rate(2005:0.58 per 100 000;2021:1.59 per 100 000)and proportion(2005:14.80％;2021:44.31％)in the age group of 60 years or a-bove showed an increasing trend over the years(AAPC=10.52％,95％CI:4.38％-16.66％;AAPC=175.98％,95％CI:143.20％-208.75％).HFRS cases exhibited significant spatial clustering(P＜0.05).The hotspots of HFRS in Hubei Province shifted from the northern region(Xiangyang,Suizhou,Jingmen)in 2005-2007 to the southern region(Qianjiang,Xiantao,Tianmen,Jingzhou)in 2020-2021.Older age(OR=1.02,95％CI:1.01-1.04)and the period of 2005-2008 versus 2017-2021(OR=0.98,95％CI:0.97-0.99)were associated with relatively higher risk of HFRS mortality.In recent years,the HFRS epidemic in Hubei Province has continued to escalate,and areas such as Qianjiang City and other ares in the middle and lower reaches of the Yangtze River have experienced high incidence rates.The population 60 years of age or above is gradually becoming more susceptible to the disease.Targeted measures should be implemented to curb the rising trend of HFRS.

Objective:To establish a mesenchymal stem cell(MSC)-based in vitro cell model for the evaluation of mouse bone marrow acute graft-versus-host disease(aGVHD).Methods:Female C57BL/6N mice aged 6-8 weeks were used as bone marrow and lymphocyte donors,and female BALB/c mice aged 6-8 weeks were used as aGVHD recipients.The recipient mouse received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1× 107/mouse)in 6-8 hours post irradiation to establish a bone marrow transplantation(BMT)mouse model(n=20).In addition,the recipient mice received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1 × 107/mouse)and spleen lymphocytes(2 × 106/mouse)in 6-8 hours post irradiation to establish a mouse aGVHD model(n=20).On the day 7 after modeling,the recipient mice were anesthetized and the blood was harvested post eyeball enucleation.The serum was collected by centrifugation.Mouse MSCs were isolated and cultured with the addition of 2％,5％,and 10％recipient serum from BMT group or aGVHD group respectively.The colony-forming unit-fibroblast(CFU-F)experiment was performed to evaluate the potential effects of serums on the self-renewal ability of MSC.The expression of CD29 and CD105 of MSC was evaluated by immunofluorescence staining.In addition,the expression of self-renewal-related genes including Oct-4,Sox-2,and Nanog in MSC was detected by real-time fluorescence quantitative PCR(RT-qPCR).Results:We successfully established an in vitro cell model that could mimic the bone marrow microenvironment damage of the mouse with aGVHD.CFU-F assay showed that,on day 7 after the culture,compared with the BMT group,MSC colony formation ability of aGVHD serum concentrations groups of 2％and 5％was significantly reduced(P＜0.05);after the culture,at day 14,compared with the BMT group,MSC colony formation ability in different aGVHD serum concentration was significantly reduced(P＜0.05).The immunofluorescence staining showed that,compared with the BMT group,the proportion of MSC surface molecules CD29+and CD 105+cells was significantly dereased in the aGVHD serum concentration group(P＜0.05),the most significant difference was at a serum concentration of 10％(P＜0.001,P＜0.01).The results of RT-qPCR detection showed that the expression of the MSC self-renewal-related genes Oct-4,Sox-2,and Nanog was decreased,the most significant difference was observed at an aGVHD serum concentration of 10％(P＜0.01,P＜0.001,P＜0.001).Conclusion:By co-culturing different concentrations of mouse aGVHD serum and mouse MSC,we found that the addition of mouse aGVHD serum at different concentrations impaired the MSC self-renewal ability,which providing a new tool for the field of aGVHD bone marrow microenvironment damage.

Eleven compounds were isolated from the ethyl acetate fraction of the 95% aqueous ethanol extract of the roots of Sophora tonkinensis by silica gel, ODS, Sephadex LH-20 column chromatography, and semi-preparative RP-HPLC. Their structures were identified as 7-hydroxy-8-isopentenylchromone (1), furo[2,3-f]-1,3-benzodioxole-7-carboxylic acid (2), 6-[3-(2′,4′-dihydroxyphenyl)acryloyl]-7-hydroxy-2,2-dimethyl-8-(3-methyl-2-butenyl)-2H-benzopyran (3), flemichapparin B (4), tectorigenin (5), genistein (6), 6-hydroxy-1,3-benzodioxole-5-carboxylic acid (7), vanillic acid (8), protocatechuic acid (9), 2,4-dihydroxybenzoic acid (10), and p-hydroxybenzoic acid (11) through extensive spectroscopic data (IR, UV, HR-ESI-MS, and NMR spectra). Among them, compounds 1 and 2 were new compounds. In addition, compound 3 showed significant α-glucosidase and protein tyrosine phosphatase-1B (PTP1B) inhibitory activities with IC₅₀ values of 5.595 and 0.320 μmol·L^-1, respectively.

Ferroptosis is a newly discovered method of programmed cell death. Current studies have shown that activation of ferroptosis-related pathways can inhibit the growth and proliferation of tumor cells and reverse their drug resistance. Oral cancer is a common malignant tumor with a high recurrence rate and high drug resistance. Inducing ferroptosis is a potential treatment strategy. There are still many uncertainties in the application of ferroptosis in the treatment of oral cancer, which need to be further explored. This article systematically introduces the mechanism of ferroptosis and its recent progress in oral cancer treatment to provide new mechanisms and methods for the clinical treatment of oral cancer. Current research shows that the mechanism of ferroptosis is mainly related to amino acid metabolism, Fe2+ metabolism, and lipid metabolism. Ferroptosis in oral cancer cells can reverse drug resistance in cancer cells and improve the activity of immune cells. New drugs, such as curcumin analogs and triptolide, can induce ferroptosis in oral cancer, and the development of nanomaterials has improved the utilization rate of drugs. Inhibiting the expression of the ferroptosis-related factors SLC7A11, NF-E2-related factor 2 (Nrf2), and ferritin heavy chain 1 (FTH1) can promote ferroptosis in oral cancer cells. It is a potential target for the clinical treatment of oral cancer, but its translation into clinical practice still needs further research.

For the treatment of an intertrochanteric fracture combined with femoral head necrosis in middle-age patients, it has been controversial whether to perform fracture reduction and fixation first then total hip replacement, or direct total hip replacement. We present a rare case of 53-year-old male patient suffered from bilateral intertrochanteric fracture caused by a road traffic injury. The patient had a history of femoral head necrosis for eight years, and the Harris score was 30. We performed total hip replacement with prolonged biologic shank prostheses for primary repair. One year after the surgery, nearly full range of motion was achieved without instability (active flexion angle of 110°, extension angle of 20°, adduction angle of 40°, abduction angle of 40°, internal rotation angle of 25°, and external rotation angle of 40°). The Harris score was 85. For the middle-aged patient with unstable intertrochanteric fractures and osteonecrosis of the femoral head, we can choose primary repair for concurrent bilateral intertrochanteric fracture and femoral head necrosis with prolonged shank biologic total hip replacement.
Male ; Middle Aged ; Humans ; Arthroplasty, Replacement, Hip/methods* ; Femur Head/surgery* ; Femur Head Necrosis/surgery* ; Fracture Fixation, Internal/methods* ; Hip Fractures/surgery* ; Biological Products ; Treatment Outcome ; Retrospective Studies

Objective: To establish and optimize a TaqMan-probe quantitative real-time PCR (qPCR) assay for the detection of 7 important Rickettsiales pathogens and simultaneous identification of the infection types. Methods: Based on the ompB gene of Rickettsia prowazekii, Rickettsia mooseri and spotted fever group rickettsiae, the groEL gene of Orientia tsutsugamushi, the 16S rRNA of Ehrlichia chaffeensis, the gltA gene of Anaplasma phagocytophilum and the com1 gene of Coxiella burnetii, we synthesized primers and TaqMan-probes and optimized the reaction system and reaction process to same solution. The sensitivity, specificity and reproducibility of this assay were evaluated and the assay was used for the detection of simulated and actual samples. Results: The Ct value of the standard curves of the 7 pathogens showed a good linear relationship with the number of DNA copies (all R² >0.990 0), the minimum detection limit was 10 copies/μl, showing good specificity. In the 96 tick nucleic acid extracts, Coxiella burnetii was detected in 1 sampleand spotted fever group Rickettsiae was detected in 3 samples. In the 80 blood samples from patients with undefined febrile illness, Orientia tsutsugamushi was detected in 1 sample and spotted fever group rickettsiae was detected in 2 samples. Conclusions: In this study, based on the established TaqMan-probe qPCR assay, the reaction system and reaction condition of the 7 important pathogens of Rickettsiales were optimized to the same solution. This method overcomes the shortcomings of using different reaction systems and reaction conditions for different pathogens, which can precisely identify the species of 7 important pathogens of Rickettsiales in clinical sample detections and is important for the infection type identification and laboratory detection time reduction to facilitate precise treatment of the patients.
Humans ; Rickettsiales ; Real-Time Polymerase Chain Reaction ; RNA, Ribosomal, 16S ; Reproducibility of Results ; Orientia tsutsugamushi ; Spotted Fever Group Rickettsiosis

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen of coronavirus disease 2019. Diagnostic methods based on the clustered regularly interspaced short palindromic repeats (CRISPR) have been developed to detect SARSCoV-2 rapidly. Therefore, a systematic review and meta-analysis were performed to assess the diagnostic accuracy of CRISPR for detecting SARS-CoV-2 infection. Materials and Methods: Studies published before August 2021 were retrieved from four databases, using the keywords “SARS-CoV-2” and “CRISPR.” Data were collected from these publications, and the sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic curve was plotted for analysis with MetaDiSc 1.4. The Stata 15.0 software was used to draw Deeks’ funnel plots to evaluate publication bias. Results: We performed a pooled analysis of 38 independent studies shown in 30 publications. The reference standard was reverse transcription-quantitative PCR. The results indicated that the sensitivity of CRISPR-based methods for diagnosis was 0.94 (95% CI 0.93–0.95), the specificity was 0.98 (95% CI 0.97–0.99), the PLR was 34.03 (95% CI 20.81–55.66), the NLR was 0.08 (95% CI 0.06– 0.10), and the DOR was 575.74 (95% CI 382.36–866.95). The area under the curve was 0.9894. Conclusion Studies indicate that a diagnostic method based on CRISPR has high sensitivity and specificity. Therefore, this would be a potential diagnostic tool to improve the accuracy of SARS-CoV-2 detection.

AIM: To evaluate the effect of 0.02% mitomycin-C(MMC)on the corneal density after transepithelial photorefractive keratectomy(Trans-PRK). METHODS: Retrospective case analysis. Selected 28 patients with 56 eyes in moderate myopia who underwent Trans-PRK surgery from January 2021 to June 2021 in our hospital. They were divided into MMC group in 28 eyes with a combination of 0.02% MMC 20s during the surgery and the control group in 28 eyes was not use MMC during the surgery. The Pentacam anterior segment analyzer was used to measured the corneal density in different diameter ranges and different thickness layers before and after surgery at 14d, and after surgery at 1 and 3mo.RESULTS: The total corneal density value of MMC group was 16.60(15.70,17.10 )before the surgery, after the surgery at 14d was 16.63(15.90,17.50 ), at 1mo was 16.57(15.10,16.70 ), at 3mo was 16.04(14.60,16.60 ). The total corneal density value of control group was 16.30(15.50,17.30 )before the surgery, after the surgery at 14d was 16.20(15.20,17.10 ), at 1mo was 16.08(14.90,16.40 )and at 3mo was 15.60(14.60,16.40 ). In the zone of 0-2mm diameter was centered on the corneal vertex, the corneal density of the two groups at 14d after the surgery was higher than those before surgery(P<0.001 ). In the zone of 2-6mm diameter, the corneal density of the two groups at 1mo and 3mo after surgery was higher than those before the surgery(P<0.001). In the zone of 6-10mm, the corneal density of the two groups at 14d, 1 and 3mo after surgery was higher than those before the surgery(P<0.001). In the layer of anterior 120 μm, the corneal density of the two groups at 1mo and 3mo after the surgery was decreased than that before surgery(P<0.01). In the middle layer, the corneal density of the two groups at 1mo after the surgery was decreased than those before surgery(P<0.01).CONCLUSION:The use of 0.02% MMC during the operation can reduce the corneal density and increase the corneal light transmittance in the early postoperative period. The occurrence and prognosis of haze can be effectively quantified by observing the changes of corneal optical density in different ranges in different time periods after operation.

Extranodal natural killer/T-cell lymphoma (ENKTCL) is the subtype of non-Hodgkin lymphoma with high heterogeneity and invasiveness. Though most ENKTCL patients are present as early-stage at diagnosis, clinical prognosis significantly differs due to the limitations of clinical staging. Radiotherapy (RT) and chemotherapy (CT) are the first-line treatments for early ENKTCL patients. However, there is no consensus on the combined modalities of RT and CT, and their optimal strategy. With the continuous renewal of clinical staging and prognostic models, early-stage ENKTCL patients tend to accept risk-adapted treatment with proper stratification. In this review, the latest research progresses on clinical staging, prognostic models and treatment were retrospectively analyzed, aiming to provide references for clinical decision-making.