BACKGROUND:Reducing the rate of abnormal fertilization is an effective approach to improving the efficacy of in vitro fertilization and reducing patients'financial strain.However,the current research on abnormal fertilization has focused on exploring the types of prokaryotic nuclei and their generation mechanisms,as well as analyzing embryos formed by abnormal fertilization,chromosomal ploidy and utilization value.There is a lack of clinical prediction models for abnormal fertilization based on retrospective studies. OBJECTIVE:To construct a nomogram model to predict abnormal female factors in in vitro fertilization. METHODS:A total of 5 075 patients undergoing treatment for conventional in vitro fertilization at Nanxishan Hospital of Guangxi Zhuang Autonomous Region from March 2017 to March 2022 were retrospectively analyzed.The male confounders were calibrated on a 1:1 propensity score with a match tolerance of 0.02,and 1 672 cases were successfully matched.According to the Vienna Consensus,patients with≥60%normal fertilization capacity were included in the normal fertilization group(n=836)and those with<60%normal fertilization capacity were included in the abnormal fertilization group(n=836).The model and validation groups were obtained by random sampling at a ratio of 7:3.Factors related to the occurrence of abnormal fertilization following conventional in vitro fertilization in the model group were screened using univariate analysis and the best matching factors were selected using the Least Absolute Shrinkage and Selection Operator(LASSO)and included in a multifactorial forward stepwise Logistic regression to identify their independent influencing factors and plot a nomogram.Finally,the prediction model was validated for discrimination,accuracy and clinical application efficacy using receiver operating characteristic curves,calibration curves,clinical decision curves and clinical impact curves. RESULTS AND CONCLUSION:The univariate analysis indicated the factors influencing the occurrence of abnormal fertilization were age,controlled ovarian hyperstimulation protocol,number of assisted pregnancies,years of infertility,infertility factors,anti-mullerian hormone,sinus follicle count,basal luteinizing hormone,luteinizing hormone concentration on the human chorionic gonadotropin day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).LASSO regression further identified the best matching factors,including age,microstimulation protocol,number of assisted pregnancies,years of infertility,anti-mullerian hormone,luteinizing hormone level on human chorionic gonadotropin injection day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).Multifactorial forward stepwise Logistic regression results showed that age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day were independent influencing factors for the occurrence of abnormal fertilization following conventional in vitro fertilization.The receiver operating characteristic curves showed an area under the curve of 0.761(0.746,0.777)for the model group and 0.767(0.733,0.801)for the validation group,indicating that the model has good discrimination.The mean absolute error of the calibration curve was 0.044,and the Hosmer-Lemeshow test indicated that there was no significant difference between the predicted probability of abnormal fertilization and the actual probability of abnormal fertilization(P>0.05),indicating the prediction model has good consistency and accuracy.The clinical decision curves and clinical impact curves showed that the model and validation groups had the maximum net clinical benefit at valve probability values of 0.00-0.52 and 0.00-0.48,respectively,and there was a good clinical application efficacy in this valve probability range.To conclude,the nomogram model has good discrimination and accuracy as well as clinical application efficacy for predicting the occurrence of abnormal fertilization in women undergoing conventional in vitro fertilization based on age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day.

Background Polycyclic aromatic hydrocarbons (PAHs), one of the main components of fine particulate matter (PM_2.5), have a certain impact on ambient air quality, and long-term exposure to PAHs may pose potential health risks to human beings. Objective To identify the distribution characteristics and sources of PAHs in atmospheric PM_2.5 in a district of Taizhou City from 2019 to 2021, and to evaluate the health risks of PAHs to the population in the area through the inhalation pathway. Methods From 2019 to 2021, air PM_2.5 sampling was carried out at a state-controlled surveillance point in a district of Taizhou City for 7 consecutive days on the 10th-16th of each month, the sampling time was 24 h·d⁻¹, and the sampling flow rate was 100 L·min⁻¹. PM_2.5 mass concentration was calculated by gravimetric method. A total of 16 PAHs were determined by ultrasonic extraction-liquid chromatography. Kruskal-Wallis H test was used to compare the distribution charac teristics of PAHs concentrations by years and seasons, characteristic ratio and principal component analysis (PCA) was used to analyze their sources, and a lifetime carcinogenic risk (ILCR) model was used to assess the health risk of PAHs. Results From 2019 to 2021, the annual average concentrations [M (P₂₅, P₇₅)] of ∑PAHs in atmospheric PM_2.5 in the selected district of Taizhou City were 6.52 (2.46, 10.59), 8.52 (4.56, 12.29), and 3.72 (1.51, 7.11) ng·m⁻³, respectively, and the annual benzo[a]pyrene (BaP) excess rates (national limit: 1 ng·m⁻³) were 27.38% (23/84), 47.62% (40/84), and 19.04% (16/84), respectively, both presenting 2020> 2019 > 2021 (P<0.001, P<0.05). The ∑PAHs concentration distribution showed a seasonal variation, with the highest value in winter and the lowest value in summer (P<0.05). Among the atmospheric PM_2.5 samples, the proportion of 5-ring PAHs was the highest, the proportion of 2-3-ring PAHs was the lowest; the proportion of 2-4-ring PAHs showed a yearly upward trend, and the proportion of 5-6-ring PAHs showed yearly downward trend (P<0.05). The characteristic ratio and PCA results suggested that the sources of sampled PAHs were mainly mixed sources such as dust, fossil fuel (natural gas), coal combustion, industrial emissions, and motor vehicle exhaust emissions. The ILCR (R_ILCR) of PAHs by inhalation for men, women, and children were 1.83×10⁻⁶, 2.35×10⁻⁶, and 2.04×10⁻⁶, respectively, and the annual average R_ILCR was 2.07×10⁻⁶, all greater than 1×10⁻⁶. Conclusion For the sampled time period, the main sources of PAHs pollution in atmospheric PM_2.5 in the target district of Taizhou City are dust, fossil fuel (natural gas), coal combustion, industrial emissions, motor vehicle emissions, etc., and PAHs may have a potential carcinogenic risk to local residents.

Objective By analyzing the clinical characteristics and related factors of treatment outcomes in patients with nontuberculous mycobacterial pulmonary disease(NTM-PD)in Taizhou,this study provided reference for the management,diagnosis and treatment of NTM-PD.Methods Clinical characteristics of 167 patients with NTM-PD isolated in Taizhou Hospital of Zhejiang Province from January 2016 to December 2021 were retrospectively analyzed.The differences in clinical characteristics were compared between cured group and failed group of 83 cases with Mycobacterium avium complex pulmonary disease(MAC-PD).Results MAC-PD was the most common species among the 167 cases of NTM-PD,accounting for 94.6％,88 patients were treated.The cure rate was 47.7％.Compared with cured group,the patients in failed group had statistical differences in body mass index(BMI)≤ 18.5kg/m2,acid-fast bacilli smear-positive,combined with previous pulmonary tuberculosis,imaging with fibrous-cavernous type and unstandardized medication(P＜0.05).Conclusion MAC-PD is the most common among NTM-PD patients in Taizhou.BMI ≤ 18.5kg/m2,acid-fast bacilli smear-positive,combined with previous pulmonary tuberculosis,imaging with fibrous-cavernous type and unstandardized medication of MAC-PD were more difficult to treat.

Viruses, the smallest microorganisms, continue to present an escalating threat to human health, being the leading cause of mortality worldwide. Over the decades, although significant progress has been made in the development of therapies and vaccines against viral diseases, the need for effective antiviral interventions remains urgent. This urgency stems from the lack of effective vaccines, the severe side effects associated with current drugs, and the emergence of drug-resistant viral strains. Natural plants, particularly traditionally-used herbs, are often considered an excellent source of medicinal drugs with potent antiviral efficacy, as well as a substantial safety profile. Scutellaria baicalensis, a traditional Chinese medicine, has garnered considerable attention due to its extensive investigation across diverse therapeutic areas and its demonstrated efficacy in both preclinical and clinical trials. In this review, we mainly focused on the potential antiviral activities of ingredients in Scutellaria baicalensis, shedding light on their underlying mechanisms of action and therapeutic applications in the treatment of viral infections.
Humans ; Antiviral Agents/therapeutic use* ; Scutellaria baicalensis ; Virus Diseases/drug therapy* ; Medicine, Chinese Traditional

Objective:To assess the predictive performance of the risk of cardiovascular diseases (CVD) derived from the China Kadoorie Biobank (CKB-CVD) model, prediction for atherosclerotic cardiovascular disease (ASCVD) risk in China (China-PAR) model, and the risk of fatal and nonfatal ischemic cardiovascular diseases derived from the USA-People′s Republic of China Collaborative Study (USA-PRC) model in Chinese Multi-provincial Cohort Study (CMCS).Methods:In this prospective cohort study, a total of 21 948 individuals aged ≥35 years without CVD were selected from 8 provinces and cities in China during the CMCS survey from 1992 to 2005 for 10-year follow-up. The occurrence of CVD or ASCVD events during the follow-up period was used as the gold standard. The CKB-CVD and China-PAR models were used to calculate the predicted risk of CVD events, while the USA-PRC model was used to calculate the predicted risk of ASCVD events. The discrimination of the models was evaluated using the C-statistic, and the calibration was assessed using the Hosmer-Lemeshow χ2 test and decile plot. Results:During the 10-year follow-up, a total of 955 (4.4%) CVD events, including 791 (3.6%) ASCVD events, were recorded among the study participants. The C-index for the CKB-CVD, China-PAR, and USA-PRC models were 0.775 (95% CI: 0.757-0.793), 0.781 (95% CI: 0.763-0.798), and 0.769 (95% CI: 0.750-0.789) for men, and 0.762 (95% CI: 0.737-0.788), 0.769 (95% CI: 0.745-0.794), and 0.767 (95% CI: 0.741-0.794) for women, respectively. China-PAR model showed good calibration for men ( χ2=2.20), however, both CKB-CVD and USA-PRC models demonstrated poor calibration in both men and women ( χ2>20). The results indicated that the CKB-CVD model overestimated the risk of CVD events in both males and females, while the China-PAR model underestimated the risk in females. Furthermore, the USA-PRC model underestimated the risk of ASCVD in both males and females in most decile groups, but overestimated the risk in the highest decile group. Conclusion:The CKB-CVD, China-PAR, and USA-PRC risk assessment models show some degree of deviation from the actual risk of events in the CMCS cohort, but all exhibit good discrimination.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

Objective:To investigate the value of plasma Epstein-Barr virus (EBV) DNA detection in the screening of nasopharyngeal carcinoma (NPC) and its clinical application in non-high-risk areas.Methods:Plasma EBV DNA results in 1 153 newly diagnosed nasopharyngeal carcinoma patients who were treated in Sichuan Cancer Hospital from 2015 to 2020 and 244 healthy control cases with matched sex and age were retrospectively analyzed. EBV DNA were detected by quantitative real-time PCR. Positive rate of EBV DNA was determined by the cutoff value of 400 (≥400 copies/ml as positive) and optimization threshold method (presence of S amplification curve as positive). Further analyses were conducted to compare EBV DNA load in different clinical stage, TNM stage and regions distribution characteristics. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of the cutoff value of 400 and optimization threshold method for NPC.Results:Compared with healthy controls, EBV DNA increased significantly in newly diagnosed NPC patients ( P<0.001). Both evaluation methods revealed that the EBV DNA positive percentage increased with TNM and clinical stage ( P<0.001). With 400 copies/ml as cutoff value, the diagnostic sensitivity and specificity were 40.85% and 100%, respectively. The area under the curve was 0.704 (95% CI 0.676-0.733, P<0.001). Evaluated by the optimization threshold method, the sensitivity and specificity could improve to 82.0% and 99.2%, respectively, and the area under the curve reached 0.910 (95% CI 0.894-0.924, P<0.001). Conclusions:In the low prevalence area of nasopharyngeal carcinoma, the sensitivity for diagnosis of nasopharyngeal carcinoma is only 40.9% by the 400 copies/ml cutoff value method. The optimization threshold method is a better choice to improve the diagnostic sensitivity without lowering the diagnostic specificity.

Objective:To investigate the clinicopathologic features, differential diagnosis, immunohistochemical profiles and molecular characteristics of primary extraskeletal osteosarcoma (ESOS).Methods:Ten cases of ESOS diagnosed and treated in Fujian Provincial Hospital, Fuzhou, China from January 2003 to January 2019 were collected and subjected to immunohistochemical staining and molecular analyses. The patients were followed up by telephone interview. Relative literature was also reviewed to assess the characteristics of this tumor.Results:The ten cases occurred in 3 women and 7 men, aged from 36 to 85 years (median, 60 years). The sizes of these tumors ranged from 5.5 to 17.5 cm (median, 11.0 cm). Histologically, at low magnification, the tumors were nodular, leafy and lobulated. They were composed of spindle cells, neoplastic osteoid cells, and cartilage tissues, with unequally-proportional mixture of these components. The three components intermingled with each other. Immunohistochemistry profiling showed that the tumor cells were positive for SATB2 (9/9), while α-SMA (4/10) and EMA (1/10) stains were focally positive. Ki-67 proliferation index was 10%?50%. Desmin, CD68, S-100 protein, SOX10, HMB45, CD117, DOG1, CD34, CKpan, GATA3 and PAX8 stains were negative. MDM2/CDK4 gene amplification signals were not detected in the 6 cases (0/6), which were subjected to the FISH. The SSX18 break-apart signal and the C-KIT and PDGFR-α mutations were not detected (0/5 and 0/3, respectively). Conclusions:Primary ESOS is an extra-osseous osteogenic tumor. The diagnosis is mainly dependent on clinical, radiological and pathological characteristics. Immunohistochemistry and molecular profiling are helpful for making the correct diagnosis.

Objective: The aim of this study is to investigate the effect of sublingual immunotherapy with Dermatophagoides Farinae on the expression of specific IgG4（sIgG4） in patients with allergic rhinitis （AR） in Hainan area. Method: Seventy-two patients with dust-mite allergic rhinitis, all three generations of whom were local islanders in Hainan, were randomly divided into control group（36 cases） and SLIT group（36 cases）. sIgG4 and sIgE expression levels were detected before treatment, 6 months after treatment, 12 months after treatment, and 18 months after treatment. The patient's symptom score, medication score, VAS score and adverse reactions was also assessed. Finally, through statistical analysis of the relevant data collected at 4 time points in the two groups of patients, the efficacy, safety and changes of sIgG4 antibody expression level in patients with allergic rhinitis receiving sublingual specific immunotherapy in Hainan were observed. Result: Symptoms scores, medication scores and VAS scores were significantly improved in the SLIT group after treatment compared with before treatment（P<0.05）, and serum sIgG4 increased significantly（P<0.01）, serum sIgE showed no significant change（P>0.05）. In the control group, symptom scores, medication scores and VAS scores were also significantly improved compared with before treatment（P<0.05）, while serum sIgG4 and sIgE showed no significant change（P>0.05）. When comparing the two groups, Symptoms scores, medication scores and VAS scores of the SLIT group were significantly lower than those of the control group at 12 months and 18 months after treatment（P<0.05）. sIgG4 expression levels in the SLIT group were significantly higher than those in the control group after 6, 12 and 18 months of treatment（P<0.01）. There was no significant difference in sIgE expression level between the two groups（P>0.05）. No severe systemic adverse reactions occurred in the two groups, and 3 patients showed mild adverse reactions in the SLIT group. Conclusion Sublingual immunotherapy of Dermatophagoides Farinae was effective and could increase the expression of sIgG4 in patients with Dermatophagoides farinae AR, sIgG4 is expected to be an immunological marker for the objective evaluation of the clinical efficacy of Hapten.

The aim of this study is to investigate the effect of sublingual immunotherapy with Dermatophagoides Farinae on the expression of specific IgG4（sIgG4） in patients with allergic rhinitis （AR） in Hainan area. Seventy-two patients with dust-mite allergic rhinitis, all three generations of whom were local islanders in Hainan, were randomly divided into control group（36 cases） and SLIT group（36 cases）. sIgG4 and sIgE expression levels were detected before treatment, 6 months after treatment, 12 months after treatment, and 18 months after treatment. The patient's symptom score, medication score, VAS score and adverse reactions was also assessed. Finally, through statistical analysis of the relevant data collected at 4 time points in the two groups of patients, the efficacy, safety and changes of sIgG4 antibody expression level in patients with allergic rhinitis receiving sublingual specific immunotherapy in Hainan were observed. Symptoms scores, medication scores and VAS scores were significantly improved in the SLIT group after treatment compared with before treatment（<0.05）, and serum sIgG4 increased significantly（<0.01）, serum sIgE showed no significant change（>0.05）. In the control group, symptom scores, medication scores and VAS scores were also significantly improved compared with before treatment（<0.05）, while serum sIgG4 and sIgE showed no significant change（>0.05）. When comparing the two groups, Symptoms scores, medication scores and VAS scores of the SLIT group were significantly lower than those of the control group at 12 months and 18 months after treatment（<0.05）. sIgG4 expression levels in the SLIT group were significantly higher than those in the control group after 6, 12 and 18 months of treatment（<0.01）. There was no significant difference in sIgE expression level between the two groups（>0.05）. No severe systemic adverse reactions occurred in the two groups, and 3 patients showed mild adverse reactions in the SLIT group. Sublingual immunotherapy of Dermatophagoides Farinae was effective and could increase the expression of sIgG4 in patients with Dermatophagoides farinae AR, sIgG4 is expected to be an immunological marker for the objective evaluation of the clinical efficacy of Hapten.