Background Fine particulate matter (PM_2.5) monitoring stations may generate missing data for a certain period of time due to various factors. This data loss will adversely affect air quality assessment and pollution control decision-making. Objective To propose an inverse distance weighted (IDW) spatiotemporal interpolation method based on particle swarm optimization (PSO) to interpolate and fill missing PM_2.5 spatiotemporal sequence data and increase interpolation accuracy. Methods An interpolation experiment was designed into two parts. The first part used hourly PM_2.5 observational data from four moments on January 1, 2017 in the Yangtze River Delta region. The second part employed daily PM_2.5 observational data from the first 10 d of January 2017 in the Beijing-Tianjin-Hebei region. Interpolation accuracy was evaluated using four metrics: root mean square error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE), and mean relative error (MRE). Results IDW spatiotemporal interpolation method optimized with PSO significantly improved the accuracy of filling missing PM_2.5 spatiotemporal sequence data. In the hourly-scale experiment conducted in the Yangtze River Delta region, compared to a distance index of 2, the accuracy metrics RMSE, MAE, MAPE, and MRE generated by the proposed method improved on average by 0.17 μg·m⁻³, 0.27 μg·m⁻³, 0.17%, and 0.01%, respectively. The PM_2.5 spatial field maps generated for four moments based on this method clearly illustrated the spatiotemporal distribution characteristics of hourly PM_2.5 concentrations in the Yangtze River Delta region. In the daily-scale experiment conducted in the Beijing-Tianjin-Hebei region, the PSO-optimized distance index outperformed the traditional method, with interpolation accuracy improvements of approximately 0.215 μg·m⁻³, 0.283 μg·m⁻³, 0.174%, and 0.014%, respectively. Furthermore, the seasonal PM_2.5 spatial field maps generated by this method revealed the spatiotemporal distribution characteristics of PM_2.5 concentrations in the Beijing-Tianjin-Hebei region across different seasons, further validating the effectiveness and applicability of this method. Conclusion The IDW spatiotemporal interpolation method optimized with PSO is highly accurate and reliable for interpolating the missing data in the Yangtze River Delta region and the Beijing-Tianjin-Hebei region, providing valuable insights for air pollution control and public health protection.

Objective To analyze the application value of cervical vascular color Doppler ultrasound com-bined with serum microRNA-222-3p(miR-222-3p)and microRNA-206(miR-206)in the diagnosis of carotid artery stenosis in patients with cerebral infarction.Methods A total of 90 patients with cerebral infarction ad-mitted to this hospital from July 2018 to July 2022 were selected as the study group,and were divided into mild stenosis group(29 cases),moderate stenosis group(35 cases),and severe stenosis group(26 cases)ac-cording to the degree of carotid artery stenosis.In addition,96 healthy people who underwent physical exami-nation in the hospital were selected as the control group.Real-time fluorescence quantitative PCR was used to detect the levels of serum miR-222-3p and miR-206 in each group.All patients with cerebral infarction under-went cervical vascular color Doppler ultrasound examination,and the clinical data of patients with different de-grees of stenosis were analyzed.Multivariate Logistic regression was used to analyze the factors affecting the degree of carotid artery stenosis in patients with cerebral infarction.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of carotid ultrasound indicators,serum miR-222-3p and miR-206 levels for the degree of carotid artery stenosis in patients with cerebral infarction.Results Compared with the control group,the study group had a significant increase in the serum level of miR-222-3p and a sig-nificant reduction in the serum level of miR-206(P＜0.05).Compared with the mild stenosis group,the peak systolic velocity(PSV),end diastolic volume(EDV)and serum miR-222-3p level were increased,and the ser-um miR-206 level was decreased in the moderate stenosis group and the severe stenosis group(P＜0.05).Compared with moderate stenosis group,EVD,PSV and serum miR-222-3p levels were significantly in-creased,and miR-206 level was decreased in severe stenosis group(P＜0.05).EVD,PSV,serum miR-222-3p level were risk factors for carotid artery stenosis in patients with cerebral infarction,and serum miR-206 level was a protective factor for carotid artery stenosis in patients with cerebral infarction(P＜0.05).The area un-der the curve of EVD,PSV combined with serum miR-222-3p and miR-206 in diagnosing the degree of carotid artery stenosis in patients with cerebral infarction was 0.991,and the sensitivity and specificity were 98.36％and 93.10％,respectively.It was better than that of EVD,PSV,serum miR-222-3p,and miR-206 alone(Zcombination-EVD=2.927,P=0.003,Z combination-PSV=2.834,P=0.005,Zcombination-miR-222-3p=3.300,P=0.001,Zcombination-miR-206=3.730,P＜0.001).Conclusion Cervical vascular color Doppler ultrasound combined with ser-um miR-222-3p and miR-206 has application value in the diagnosis of carotid artery stenosis in patients with cerebral infarction.

Objective:To compare the safety and efficacy of high-dose- rate interstitial brachytherapy and particle implantation radiotherapy in the treatment of lymph nodes with pelvic metastases in the field after external radiotherapy.Methods:Clinical data of 42 patients with residual or newly metastatic pelvic lymph nodes after radiotherapy at Cangzhou Integrated Traditional Chinese and Western Medicine Hospital who met the inclusion criteria from January 2017 to April 2020 were retrospectively analyzed. Among them, 12 patients were male and 30 females, aged 39-82 years, (61.6±9.64) years on average. According to the treatment method, all patients were divided into the high-dose-rate interstitial brachytherapy group ( n=18) and particle implantation radiotherapy group ( n=24). During 3-year follow-up, the local control rate (LCR), incidence of complications and overall survival (OS) were compared between two groups. Age and operation time conforming to normal distribution were analyzed by t-test. The remaining indexes were analyzed by the Chi-square test or Fisher's exact test. The OS and LCR were calculated by Kaplan-Meier method. Results:There was no significant difference in baseline data between two groups (all P>0.05). The operation time in the high-dose- rate interstitial brachytherapy group was longer than that in the particle implantation radiotherapy group [(66.39±11.07) : (45.75±9.19) min, P<0.001]. During subsequent follow-up, there was no significant difference in the LCR between two groups (1-year LCR 88.9% vs. 87.5%, P=0.927; 2-year LCR 72.2% vs. 62.5%, P=0.874). There was no significant difference in the median OS between two groups (31.6 vs. 29.8 months, P=0.798). There was no significant difference in the incidence of early complications between two groups [ (4/18) vs. 5/24 (20.8%), P=1.000]. No late complications observed. Conclusion:High-dose- rate interstitial brachytherapy yields equivalent efficacy and safety to particle implantation radiotherapy in the treatment of lymph nodes with pelvic metastases.

Objective:To analyze the cause and epidemiological characteristics of an outbreak of cutaneous anthrax in Caoxian County, Heze City, Shandong Province, and to provide scientific basis for anthrax prevention and control.Methods:Using on-site epidemiological investigation methods and the "Anthrax Epidemiological Case Investigation Form", case investigations were conducted based on the epidemiological contact history and close contacts of suspected anthrax cases reported by the national health care system ( n = 83). Scorched skin smears, diseased cattle tissues, soil samples from the slaughter site and smears from slaughter utensils were collected from cases for Real-time PCR testing and pathogenic bacteria isolation and culture, respectively. Anthrax determination criteria were carried out with reference to "Anthrax Diagnosis" (WS 283-2020). Results:A total of 13 cases of cutaneous anthrax were found in this outbreak, including 12 clinically diagnosed cases and one confirmed case (positive Real-time PCR test and isolation of a strain of Bacillus anthracis). The epidemiological investigation determined that the source of infection in this outbreak was diseased cattle, the transmission route was through slaughter of diseased cattle, contact with contaminated utensils and related cattle products, and the patients were mainly engaged in occupations related to cattle slaughter or cattle product collection and sale. A total of 84 samples were collected, including 13 skin scabs, 64 environmental samples and 7 beef samples. Thirty-six positive PCR tests were performed, with a positive rate of 42.86% (36/84). Among them, 100.00% (13/13) were positive for skin scab smear specimens, 29.69% (19/64) for environmental samples and 4/7 for beef samples. A total of 8 strains of Bacillus anthracis were isolated, including 6 environmental specimens, 1 suspected case and 1 beef strain, with an overall detection rate of 9.52% (8/84). Eighty-three close contacts were investigated. Thirteen households involved in the epidemic were disinfected by spraying (200 ml/m 2) with chlorine-containing disinfectant (5 000 mg/L), and a total of 40 households involved in the epidemic were disinfected, covering an area of about 10 765 m 2. Forty-five pieces of suspected contaminated clothing were burned and disposed of, and 152 pieces of kitchenware were soaked. Conclusions:Slaughter of infected cattle, contact with contaminated utensils and related cattle products are the main causes of this skin anthrax outbreak. Strengthening market supervision, deepening inter-animal epidemic prevention, carrying out publicity and education on anthrax prevention and control, and enhancing practitioners' awareness of disease prevention is the key to prevent anthrax from occurring.

OBJECTIVES: The prevalence of carbapenem-resistant Enterobacterales (CRE) presents a significant challenge in clinical anti-infective treatment. This study aims to investigate drug resistance and the molecular epidemiological characteristics of CRE in our area. Additionally, we seek to evaluate practicality of utilizing carbapenemase inhibitor enhancement test in clinical laboratory. METHODS: Non-repeated CREs isolated from clinical specimens at Xiangya Hospital, Central South University, were collected. Minimum inhibitory concentration (MIC) combined with Kirby-Bauer (KB) assay was used to detect the drug susceptibility of the strains, and 13 carbapenemase-producing genes were detected by PCR. The phenotype of 126 strains of carbapenemase-producing Enterobacterales identified by PCR was detected by the carbapenemase inhibitor enhancement test to understand the agreement between the method and the gold standard PCR results. RESULTS: Among 704 CRE strains examined, we observed significant drug resistance in 501 strains dentified as carbapenemase-producing Enterobacterales (CPE). Klebsiella pneumoniae was the predominant CPE strain, followed by Enterobacter cloacae and Escherichia coli. A total of 9 carbapenemase types were detected, including Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Verona integron- encoded metallo-β-lactamases (VIM), imipenemase (IMP), oxacillinase-48 (OXA-48), and rare imipenem-hydrolyzing β-lactamase (IMI), adelaide imipenemase (AIM), Bicêtre carbapenemase (BIC), and guiana extended-spectrum β-lactamase (GES). The detection rate of KPC serine carbapenemase was 61.7% (309/501). The carbapenemase inhibitor enhancement test exhibited a 100% consistency rate for the strains producing Class A serine carbapenemase and/or Class B metallo-β-lactamases. CONCLUSIONS CRE strains in Changsha, Hunan, China, are wide distribution and exhibit carbapenemase production. The main mechanism of carbapenem resistance in these bacterias is predominatly attributed to the production of KPC serine carbapenemase. The presence of GES and IMI genes carried by Enterobacterales has been detected for the first time in this region. The carbapenemase inhibitor enhancement test has been proven to be an accurate method for detecting CRE producing Class A serine carbapenemase and/or Class B metallo-β-lactamases. This method offers simpicity of operation and ease of results interpretation, making it weel-suited meeting the clinical microbiology laboratory's reguirements for the detection of serine carbapenemase and metallo-β-lactamases.
Humans ; Carbapenems/pharmacology* ; Molecular Epidemiology ; Bacterial Proteins/analysis* ; beta-Lactamases/analysis* ; Klebsiella pneumoniae/genetics* ; Escherichia coli ; Microbial Sensitivity Tests ; Serine ; Anti-Bacterial Agents/pharmacology*

OBJECTIVES: There is less clinical data on multiple myeloma (MM) in China, and the aim of this study was to collect and analyze the clinical data of newly diagnosed multiple myeloma (NDMM) patients in Hunan Province during 1 year, to understand the real clinical features and treatment outcome for Hunan Province patients with MM, and to strengthen the understanding of the standardized diagnosis process and treatment plan of MM. METHODS: The clinical data of 529 patients with NDMM in 12 large-scale general hospitals in Hunan Province from January 1 to December 31, 2019 were collected and analyzed, including baseline data, treatment regimens, duration of treatment, and adverse reactions. The clinical characteristics, treatment, and safety of patients were analyzed by SPSS 21.0. RESULTS: Among the 529 NDMM patients, the age was 33-90 (median 64) years and the male-female ratio was 1.38꞉1. The clinical features ranged from high to low were as follows: Bone pain (77.7%), anemia (66.8%), renal insufficiency (40.6%), hypercalcemia (15.1%). Typing: IgG 46.5%, IgA 24.6%, IgD 2.6%, IgM 0.8%, light chain 15.7%, double clone 3.0%, no secretion 0.6%, absence 6.2%. Staging: Durie-Salmon stage I, II, and III were 4.5%, 10.6%, 77.3%, respectively, and 40 cases (7.6%) missed this data. International Staging System (ISS) stage I, II, and III were 10.4%, 24.4%, and 47.6%, respectively, and 93 cases (17.6%) were missing. Revised International Staging System (R-ISS) stage I, II, and III were 5.5%, 27.0%, 23.1%, respectively, and 235 cases (44.4%) missed this data. Among the 98 NDMM patients in the Third Xiangya Hospital, Central South University, Durie-Salmon (DS) stage missing 2.0%, ISS stage missing 12.3%, and R-ISS stage missing 12.3%.Treatment: Among the 529 patients,475 received treatment, the rate of treatment was 89.8%; 67.4% of the patients were able to complete four courses of chemotherapy at induction phase, 90.3% of the patients received proteasome inhibitor based combination chemotherapy regimen more than once, 67.2% received immunomodulator based regimen more than once, and 59.8% of the patients received proteasome inhibitor and immunomodulator based combination chemotherapy regimen more than once. Curative: Overall response rate (ORR) and high quality response rate (HQR) of the 4-course group were better than those of the 2-course group (ORR: 85% vs 65%, P=0.006; HQR: 68.3% vs 24.0%, P<0.001). The HQR of the standard chemotherapy group was better than that of the non-standard chemotherapy group (65.1% vs 48.2%, P=0.035). Adverse reactions during treatment included hematologic toxicity (17.5%), peripheral neuropathy (24.8%), gastrointestinal adverse events (23.8%), pulmonary infection (25.9%), herpes zoster (4.6%), and venous thrombotic events (1.7%). CONCLUSIONS In 2019, the missed diagnosis rate of MM patients was high, the medium age of diagnosis was older, and the accuracy of patient diagnosis was not high. There is a great difference among medical centers, especially in the stage and risk stratified, nearly half of NDMM patients are not diagnosed with R-ISS stage; the lack of cytogenetic data needs to be supplemented by follow-up studies. A high proportion of patients with NDMM present with bone pain and anemia.Patients received treatment have higher use of chemotherapy regimens containing proteasome inhibitors and/or immunomodulators, but there is a significant gap among different medical centers, and standardized treatment needs to be strengthened. The safety during chemotherapy is controllable.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Humans ; Immunologic Factors/therapeutic use* ; Male ; Middle Aged ; Multiple Myeloma/therapy* ; Neoplasm Staging ; Pain ; Prognosis ; Proteasome Inhibitors/therapeutic use*

Objective:To explore the effect of key amino acid mutations of 3D protein in enterovirus 71 on viral proliferation, and infer the mechanism of mutation affecting viral proliferation according to the tertiary structure model of 3D protein.Methods:The proliferation characteristics of the mutant strain that was constructed by site-directed mutagenesis and reverse genetics using the pMD19T-SDLY107-EGFP constructed from the fatal strain SDLY107 as a template were measured. Meanwhile the tertiary structure of the 3D protein was predicted, and then the possible mechanism of the mutation affecting the proliferation ability of the virus was speculated according to the functional characteristics of the domain of the 3D protein.Results:Two mutant viruses, eGFP-EV-A71 (S37N) and eGFP-EV-A71 (R142K), were successfully constructed by double enzyme digestion and viral gene sequencing. The proliferation rate of the two mutant strains in RD cells was significantly lower than that of the parent strains. The 3D protein tertiary structure prediction model showed that the 3D protein consisted of three domains: "Finger" , "thumb" and "Palm" , constituting a cupped right-handed structure. S37N and R142K are located in the "thumb" domain and " finger" domain, respectively. The "thumb" and "finger" domains have important effects on the activity of 3D polymerase and the stability of protein.Conclusions:Mutations at S37N and R142K sites of EV71 3D protein decrease the replication ability of EV71, and these two mutations may affect the proliferation of EV71 virus by changing the 3D protein polymerase activity and the interactions between multiple domains.

Objective:We try to screen out predictive indicators with higher value by analyzing the differences in clinical and laboratory indicators between severe fever with thrombocytopenia syndrome (SFTS) patients in the intensive care unit (ICU) group and non-ICU group.Methods:The clinical and laboratory index data of 69 SFTS patients diagnosed in the laboratory in a hospital from June to December 2019 were retrospectively collected. According to the clinical outcome of the patients, they were divided into ICU and non-ICU groups. The differences in clinical manifestations and laboratory indicators between the two groups were analyzed. The receiver operating characteristic curve (ROC) was used to screen the more valuable predictive indicators.Results:Compared with the non-ICU group, ICU group SFTS patients had significantly higher procalcitonin (PCT), C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), leucine aminopeptidase (LAP), glutamate dehydrogenase (GDH), adenosine deaminase (ADA), cystatin C (Cys C), α-hydroxybutyrate dehydrogenase (α-HBDH), creatine kinase (CK), lactate dehydrogenase (LDH) levels ( W=530.0, P=0.003; W=496.5, P=0.015; W=496.0, P=0.015; W=535.5, P=0.002; W=545.5, P=0.001; W=498.5, P=0.013; W=537.0, P=0.002; W=523.0, P=0.004; W=512.0, P=0.007; W=502.0, P=0.012; W=486.0, P=0.023; W=509.0, P=0.008; W=541.0, P=0.002) and significantly lower platelet count (PLT), indirect bilirubin (IBIL), albumin/globulin ratio(A/G) and superoxide dismutase (SOD) levels ( W=199.0, P=0.024; W=175.5.5, P=0.009; t=-2.9, P=0.004; W=209.5, P=0.036; t=-3.0, P=0.004). ROC result showed that ALP [area under the curve (AUC)=0.804, 95% confidence interval ( CI) (0.679~0.929)] and LDH [AUC=0.805, 95% CI (0.680~ 0.930)] have a higher value for predicting the risk of severe illness. Conclusions:Abnormal liver function, heart function, and renal function indicators in SFTS patients indicate that patients are at risk of exacerbation. Among them, ALP and LDH levels have higher predictive value for risk of severe disease, suggesting that the monitoring of patients with the above symptoms should be strengthened in the clinical nursing process.

OBJECTIVE：To explo re the potential molecular mechanism of ursolic acid in the treatment of osteoporosis （OP）. METHODS：TCMSP，PubMed database and UniProt database were used to screen potential targets of monomer compound ursolic acid. OP related target genes were searched with GeneCards database. The common target genes of component-disease were obtained by Venny 2.1 online mapping tool. The protein-protein interaction （PPI）network of component-disease common target genes was constructed by using STRING database ，and topological analysis was carried out ；the core target genes ，whose degree value was greater than the average degree value ，were screened. GO functional annotation and KEGG pathway enrichment analysis of component-disease common target genes were carried out by DAVID database. AutoDock Vina 1.1.2 software was used for molecular docking ，using protein encoded by the core target gene as receptor and ursolic acid as ligand. RESULTS ：A total of 55 ursolic acid related target genes and 4 273 OP related target genes were excavated ，with a total of 44 common target genes. PPI network with above common target genes included 44 nodes and 513 edges，with an average node degree of 23.3. There were 24 core target genes ，including VEGFA，TP53，IL6，CASP3. There were 340 GO functional items were enriched （corrected P＜ 0.05），including 263 biological processes （negative regulation of apoptosis ，etc.），25 molecular functions （protein binding ，etc.） and 52 cell components （cytosol，etc.）. There were 90 KEGG signaling pathways （corrected P＜0.05），such as tumor pathway ， hepatitis B pathway ，TNF signaling pathway ，viral carcinogenesis and phosphatidylinositol 3 kinase/protein kinase B （PI3K-Akt） signaling pathway. The binding energy between ursolic acid and 6 proteins encoded by core target genes such as TP53 was lower than －5 kcal/mol，which had strong binding activity. CONCLUSIONS ：The therapeutic effect of ursolic acid on OP may be achieved by regulating VEGFA，TP53，IL6，CASP3，JUN and other core target genes and acting on multiple key pathways such as cancer pathway ， hepatitis B and TNF signaling

Objective The role of this essay is to explore the relationship of BIM deletion polymorphism and paclitaxel intrinsic resistance in breast cancer. Methods Human breast cancer cell lines were screened by techniques of PCR and gene sequencing to detect BIM deletion polymorphism.MTS was used to detect the cytotoxic effects of paclitaxel in different cell lines. Meanwhile,levels of BIM mRNA and protein were detected by rtPCR and Western Blot. Results Comparing with the wild type cell line(MCF7),T47D was a deletion cell line with BIM deletion polymorphism and resistant to paclitaxel(T47D vs.MCF-7,IC50>30le vs.IC50=0.16 vs.02 μmol/L). Moreover,the ratio of BIM EXON3 to EXON4 was significantly increased and the level of functional BIM protein was down-regulated in T47D compared with MCF7(P < 0.05). Conclusion BIM deletion polymorphism might initiate intrinsic resistance to paclitaxel therapy in breast cancer.