OBJECTIVE To investigate the analgesic effect and potential mechanism of punicalagin on neuropathic pain （NP） rats based on the hypoxia-inducible factor-1α （HIF-1α）/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） signaling pathway. METHODS Male SD rats were randomly divided into sham operation group （18 rats） and modeling group （72 rats）. NP rat model was established by chronic constriction injury （CCI） of sciatic nerve. The successfully modeled rats were divided into NP group， 2-methoxyestradiol group （HIF-1α antagonist 10 mg/kg）， punicalagin group （300 mg/kg）， and punicalagin+dimethyloxaloglycine group （punicalagin 300 mg/kg+HIF-1α agonist 175 mg/kg）， with 18 rats in each group. Rats in each group were injected intraperitoneally and/or intragastrically with the corresponding solution or 1% dimethyl sulfoxide/normal saline， once a day， for 14 consecutive days. After the last administration， the mechanical withdrawal threshold （MWT）， thermal withdrawal latency （TWL）， the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and IL-6 in spinal cord tissue were detected； the morphological changes in the spinal dorsal horn were observed. Apoptosis rate of spinal dorsal horn neurons， the co-localization of NLRP3/ionized calcium binding adapter molecule 1 （Iba-1） （calculated by the number of NLRP3+/Iba-1+ cells） and the protein expressions of HIF-1α， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC） and caspase-1 in spinal cord tissue were detected. RESULTS Compared with the sham operation group， neurofibril in spinal dorsal horn of rats in NP group was thickened and wound into knots， and vacuolar degeneration containing silver granules was observed； the MWT and TWL were reduced or shortened； the levels of TNF-α， IL-1β and IL-6 in spinal cord tissue， the apoptosis rate of spinal dorsal horn neurons， the number of NLRP3+/Iba-1+ cells， and protein expressions of HIF-1α， NLRP3， ASC and caspase-1 were significantly increased or up-regulated （P＜0.05）. Compared with the NP group， the above indexes were significantly improved in the 2-methoxyestradiol group and punicalagin group （P＜0.05）， while dimethyloxaloglycine could significantly reverse the improvement effect of punicalagin on the above indexes （P＜0.05）. CONCLUSIONS Punicalagin can relieve pain in NP rats， and its analgesic effect may be achieved by inhibiting HIF-1α/NLRP3 signaling pathway and blocking the activation of ma0o4e@163.com NLRP3 inflammasome in spinal dorsal horn microglia.

Objective To integrate and analyze the disease burden of esophageal cancer caused by alcohol consumption in China from 1990 to 2019, along with the differences between genders, and predict the trends in disease burden changes from 2020 to 2029 to improve prevention and treatment strategies. Methods The disease burden of esophageal cancer caused by alcohol consumption in China from 1990 to 2019 was extracted and integrated from the 2019 Global Burden of Disease (GBD) database, and the corresponding trend was analyzed using the Joinpoint regression model with Joinpoint 4.9.1.0 software. The gray prediction model [GM (1, 1) ] was used to forecast the disease burden of alcohol-related esophageal cancer in China from 2020 to 2029. Results In 2019, the leading causes of esophageal cancer in China were tobacco, alcohol, high body mass index, and insufficient fruit and vegetable intake, accounting for the first to fifth positions in esophageal cancer deaths. From a gender perspective, in 2019, the death number and standardized mortality rate for males were 18.97 times and 20.00 times higher than for females, respectively. The disability-adjusted life years (DALYs) and standardized DALYs rate for males were 33.08 times and 24.78 times higher than those for females, respectively, indicating a heavier disease burden of alcohol-related esophageal cancer among Chinese males. From 1990 to 2019, the average annual percentage change (AAPC) in deaths and DALYs due to alcohol-related esophageal cancer in China was 2.08% and 1.63%, respectively, showing a continuous upward trend with statistical significance (P<0.05). The AAPC values for standardized mortality rate and standardized DALYs rate from 1990 to 2019 were –0.92% and –1.23%, respectively, showing a continuous downward trend with statistical significance (P<0.05). The population aged ≥55 years was the main group bearing the disease burden among all age groups from 1990 to 2019. The gray prediction model predicted that by 2029, the overall standardized mortality rate and standardized DALYs rate would decrease to 2.94/100 000and 67.94/100 000, with a greater decline in females than in males. Conclusion Over the past 30 years, the disease burden of alcohol-related esophageal cancer in China has slightly decreased. However, the reduction in disease burden is still lower compared to the overall decline in esophageal cancer burden, and the disease burden for males is significantly higher than for females. Focusing on prevention and treatment for males and the elderly population remains a major issue in addressing alcohol-related esophageal cancer in China.

Respiratory syncytial virus(RSV), an RNA virus, is one of the leading pathogens causing respiratory tract infections in infants, the elderly and immunocompromised people, resulting in a huge medical burden of disease worldwide every year. The fusion protein(F protein) on the surface of RSV is the main target of neutralizing antibodies, especially the discovery of its pre-fusion conformation(pre-F), which has laid a key theoretical foundation for the design of a new generation of vaccines. In view of the current limited effective prevention and treatment methods for RSV-related diseases, it is necessary to develop effective vaccines, and vaccines of various technical routes, including subunit vaccines, mRNA vaccines,live attenuated vaccines and viral vector vaccines, are under the development stage. Among them, some RSV vaccine prouducts for the elderly and pregnant women have been approved for marketing. This paper mainly outlines the problems encountered in the early development of RSV vaccines, the current status and progress of RSV vaccine research, in order to provide reference for the follow-up development, clinical evaluation and immunization strategy formulation of RSV vaccines.

Objective To explore the action mechanism of tauroursodeoxycholic acid(TUDCA)promoting intracellular clearance of Burkholderia pseudomallei(B.pseudomallei)in RAW264.7 macrophages.Methods After TUDCA of different concentrations were used to treat RAW264.7 cells pre-infected with B.pseudomallei for 8 h or not,flow cytometry was applied to detect the apoptosis of the infected and control cells.In addition,another endoplasmic reticulum stress(ERS)inhibitor 4-PBA was used to detect the apoptosis and proliferation of host cells after B.pseudomallei infection with Annexin-V/PI double staining and MTT cell proliferation assay.Furthermore,after transfected with CHOP siRNA,Western blotting and flow cytometry were employed to detect the effect of TUDCA on the expression levels of Caspase-3 and Caspase-12 and the changes in apoptotic rate after B.pseudomallei infection,respectively.Finally,the effect of TUDCA on intracellular multiplication of infected RAW264.7 cells were observed to estimate the CFU value in the presence and absence of CHOP siRNA.Results Under different concentrations of TUDCA,100 or 200 μmol/L TUDCA significantly reduced B.pseudomallei-induced apoptosis in RAW264.7 cells(P＜0.05).Meanwhile,both TUDCA and 4-PBA treatment could decrease the apoptosis induced by B.pseudomallei infection by ERS(P＜0.05).Further,the expression levels of Caspase-3 and Caspase-12 were obviously increased after B.pseudomallei infection compared with uninfected groups,but their expression levels in the siCHOP group was significantly lower than that in the siC group.Besides,flow cytometry also showed that TUDCA could reduce apoptosis induced by B.pseudomallei infection(P＜0.05),but no significant effect of TUDCA on apoptosis was observed under CHOP knockdown.Finally,intracellular CFU assay indicated that TUDCA treatment promoted the host cell clearance of B.pseudomallei(P＜0.05),but no such effect was observed in siCHOP group.Conclusion In B.pseudomallei infected RAW264.7 cells,TUDCA promotes the intracellular clearance of the bacteria by inhibiting ERS-induced apoptosis.

Objective To preliminarily investigate the association between changes in intestinal microbiota and oral microbiota of allogeneic hematopoietic stem cell transplantation(allo-HSCT)patients and early gastrointestinal acute graft versus host disease(aGVHD),and try to explore potentially effective biomarkers and provide theoretical basis for early prediction and intervention of gastrointestinal aGVHD.Methods Ten acute leukemia patients who developed gastrointestinal aGVHD within 1 month after receiving allo-HSCT in Department of Hematology of Sichuan Provincial People's Hospital from September 2021 to June 2023 were enrolled,and their fecal samples and saliva samples before and after the aGVHD were collected.16S rRNA sequencing analysis was applied for the differential changes in intestinal and oral microbiota before and after the development of early gastrointestinal aGVHD.Results ① A decrease in Bacteroides spp.and an increase in Enterococcus spp.and Enterobacteriaceae spp.in the intestinal microbiota were positively correlated with the occurrence of early upper gastrointestinal aGVHD(P＜0.05),whereas no significant difference was observed in the overall microbial diversity of the oral microbiota(P＞0.05).② LEfSe analysis of the intestinal microbiota before and after gastrointestinal aGVHD revealed an increase in Klebsiella spp.and Enterococcus spp.and a decrease in Escherichia coli;In the oral microbiota,LEfSe analysis revealed 10 microbial markers with significant difference,of which Gamma proteobacteria was the most significant.③ The difference in β-diversity of the intestinal microbiota was significant(P=0.03),whereas there was no significant difference in the α-and β-diversity of the oral microbiota.Conclusion Significant differences are found in intestinal microbiota before and after the occurrence of early gastrointestinal aGVHD in patients after Allo-HSCT,and the occurrence may have a correlation with the chang in oral microbiota.

Objective:To compare the mid-term clinical effects of AngioJet rheolytic thrombectomy assisted catheter-directed thrombolysis (ART+CDT) with catheter-directed thrombolysis (CDT) in the treatment of acute deep venous thrombosis of lower extremities.Methods:Ninety-one patients admitted to the Department from Jan 2016 to Dec 2017 were placed with inferior vena cava filters and divided into ART+CDT group (30 cases)and CDT group (61 cases). Total urokinase dosge, thrombolytic time, operative cost, length of hospital stay, detumescence rate, thrombus clearance rate, cumulative patency rate of lower limb veins, Villalta score at 2 years and 5 years, thrombosis recurrence rate and chronic venous insufficiency quality of life questionnaire were compared between the two groups.Results:The success rate of surgery was 100% in both groups, there was no mortality. There were significant differences in the short-term postoperative outcomes between the two groups in terms of total dosage of urokinase, thrombolysis time, total cost of surgery, length of hospital stay, detumescence rate, venous patency scores before and after treatment, and venous patency rate (all P<0.05). For the mid- and long-term postoperative outcomes of 2 and 5 years, there were no significant differences in the incidence of PTS, recurrence rate of thrombus, chronic venous function scale, and cumulative patency rate at 2 years (all P>0.05). Conclusions:ART+CDT has a significant advantage over CDT alone in terms of early efficacy and early reopening of blood flow in patients. Both ART+CDT and CDT have a low incidence of PTS and a low recurrence rate of thrombus in the mid-term follow-up, and both have satisfactory performance in the mid- and long-term efficacy of interventional treatment of deep venous thrombosis of lower limbs.

A 11-year old female patient with severe thalassemia, receipt a lentivirus-based cell and gene therapy (CGT) therapy in Shenzhen Children′s Hosptial on July 27th, 2021. At the two follow-up visits after discharge, patient were continuously tested positive for HIV screening through HIV Ag/Ab Combo assay (chemiluminescence Immunoassay), and the viral load results of HIV-1 nucleic acid testing (NAT) were both>5 000 copies/ml. The patient can be diagnosed with HIV infection according to the National Guideline for Detection of HIV/AIDS(2020 Revised Edition). The thorough investigation findings and supplementary experiment results indicated that the false-positive HIV-1 NAT results was caused by cross-reactivity between the target sites detected by conventional HIV-1 NAT reagents and the lentiviral vectors fragments integrated into the genome of patient′s hematopoietic stem/progenitor cells. In conclusion, it is important for laboratories to select appropriate HIV-1 NAT testing platforms which won′t cause cross-reactivity for the testing of samples from patients who have been treated with HIV-derived vectors. It is also recommended to design and develop NAT testing platforms with multiple target regions labeled by different fluorescents for HIV NAT supplementation experiment to reduce the risk of false-positive diagnoses of HIV infection.

ObjectiveTo explore the risk factors and survival analysis of chemotherapy compliance in ≥65 years old patients with non-small cell lung cancer. MethodsFrom December 2018 to August 2020， 110 patients with non-small cell lung cancer ≥65 years old in our hospital were selected for study. According to their chemotherapy compliance， the patients were divided into untreated （25 cases）， partial chemotherapy （30 cases） and full chemotherapy （55 cases）. Multivariate Cox regression was used to analyze the independent risk factors affecting the compliance of chemotherapy among the three groups， and constructed a column chart prediction model and evaluated the diagnostic effectiveness of the model using receiver operating characteristic （ROC） curves， calibration curves， and clinical decision curves. The patients were followed up until August 2023. Kaplan-Meyer survival curve and Log-rank test were used to compare the differences in survival time between the groups. ResultsThere were significant differences among the three groups in gender， long-term smoking history， education level， Charlson complication index， toxic and side effects of chemotherapy drugs and dosage， pathological type， operation mode， place of residence， payment mode， chemotherapy stage， white blood cell count and neutrophils （P<0.05）. Multivariate Cox analysis showed that patients' education level， pathological TNM stage， toxic and side effects of chemotherapy drugs and dosage， operation mode， residence， payment mode and chemotherapy stage were independent risk factors affecting chemotherapy compliance of patients with non-small cell lung cancer （all P<0.05）. There were significant differences in the survival rates between the non-chemotherapy group and the full chemotherapy group， and between the partial chemotherapy group and the full chemotherapy group （P<0.05）， but there was no significant difference between the non-chemotherapy group and the partial chemotherapy group （P>0.05）. And based on this， a prediction model was constructed， and the ROC curve was drawn to show that the AUC of the model was 0.758 （95%CI： 0.743‒0.855）， the sensitivity was 0.788， and the specificity was 0.853， indicating that the model had high discrimination， the calibration curve indicated that the prediction model had good accuracy， the clinical decision curve indicated that the predictive model had strong clinical practicality. ConclusionNSCLC tends to occur in the elderly. We should focus on the patients with low educational level， late pathological TNM stage， severe toxicity and side effects， high dose of chemotherapy drugs， having undergone open chest surgery， living in rural areas， without medical insurance， and in the period of chemotherapy consolidation and refractory relapse， so as to improve their compliance with chemotherapy.

Background Mercury, as a global heavy metal pollutant, poses a serious threat to human health. The toxicity of mercury depends on its chemical form. Distinguishing the forms of mercury in the environment is of great significance for mercury management and reducing human mercury exposure risks. Objective To establish a non-targeted metallomics method based on synchrotron radiation X-ray fluorescence (SRXRF) spectroscopy combined with machine learning to screen inorganic mercury (IHg) or methylmercury (MeHg) exposed rice plants. Methods Rice seeds were exposed to ultra-pure water (control group), 0.1 mg·L⁻¹ IHg (IHg group) or MeHg (MeHg group) solutions, respectively. After germination, the seedlings were cultured for 21 d, and rice leaves were collected, dried, weighed, and pressed. The content of metallome in rice leaves was determined by SRXRF. Machine learning models including soft independent modeling cluster analysis (SIMCA), partial least squares discriminant analysis (PLS-DA), and logistic regression (LR) were used to classify the SRXRF full spectra of different groups and find the best model to distinguish rice exposed to IHg or MeHg. Besides, characteristic elements were selected as input parameters to optimize the model by improving computing speed and reducing model calculation. Results The SRXRF spectral intensities of the control group, IHg group, and MeHg group were different, indicating that exposure to IHg and MeHg can interfere the homeostasis of metallome in rice leaves. The results of principal component analysis (PCA) of SRXRF spectra showed that the control group could be well distinguished from the mercury exposed groups, but the IHg group and the MeHg group were mostly overlapped. The accuracy rates of the three models (PLS-DA, SIMCA, and LR) were higher than 98% for the training set, higher than 95% for the validation set, and higher than 94% for the cross-validation set. Besides, the accuracy of the LR model was higher than that of the PLS-DA model and the SIMCA model. Furthermore, the accuracy was 92.05% when using characteristic elements K, Ca, Mn, Fe, and Zn selected by LR to distinguish the IHg group and the MeHg group. Compared with the full spectra model, although the prediction accuracy of the characteristic spectral model decreased, the input parameters of the model decreased by 99.51%, and precision, recall, and F1 score were above 84.48%, indicating that the model could distinguish rice exposed to different mercury forms. Conclusion Non-targeted metallomics method based on SRXRF and machine learning can be applied for high-throughput screening of rice exposed to different forms of mercury and thus decrease the risks of people being exposed to mercury.

OBJECTIVE To study the best extraction process of β-asarone from Acori Tatarinowii Rhizoma by ethanol heating reflux method, and to explore the antioxidant activity of different segments. METHODS With β-asarone from Acori Tatarinowii Rhizoma as the evaluation index to optimize the extraction method. On the basis of a single factor experiment, the effects of ethanol concentration, solid-liquid ratio and extraction time on the extraction amount of β-asarone from Acori Tatarinowii Rhizoma were investigated by orthogonal design and response surface methodology. After the optimal extraction process was determined, the antioxidant activities of different segments were studied. RESULTS The optimum extraction process of β-asarone from Acori Tatarinowii Rhizoma was as follows: ethanol concentration was 95%, solid-liquid ratio was 1∶20 g·mL–1 and extraction time was 2.5 h. Under these conditions, the extraction amount of β-asarone from Acori Tatarinowii Rhizoma was 0.918 7 mg·g–1. The results of in vitro antioxidant activity showed that the order of antioxidant capacity was ethyl acetate>petroleum ether>ethanol>n-butanol. Among them, the ethyl acetate fraction had the strongest antioxidant activity, with good ability to scavenge DPPH and ABTS free radicals, and had certain reduction ability. CONCLUSION The optimized method is stable, reliable and simple, which can be used for extraction and antioxidant activity determination of β-asarone from Acori Tatarinowii Rhizoma, and provides a basis for the further development of Acori Tatarinowii Rhizoma.