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.

ObjectiveTo comprehensively elucidate the potential mechanisms of Xiao Xumingtang （XXMT） combined with electroacupuncture （EA） collaboratively in alleviating cerebral ischemia/reperfusion （I/R） injury. MethodThe rat model of cerebral I/R injury was established using the modified suture-occluded method. Seven days after modeling， rats in the XXMT+EA groups were administered XXMT at low （15 g·kg^-1）， medium （30 g·kg^-1）， and high （60 g·kg^-1） doses， alongside daily 20-min EA treatment （stimulating acupoints GV14 and GV20）. Cerebral infarction and neuronal damage were evaluated using the Zea Longa test score， TTC staining， and TUNEL staining. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of NOD-like receptor hot protein domain related protein 3 （NLRP3）， Gasdermin D （GSDMD）， cysteinyl aspartate specific proteinase-1 （Caspase-1）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） in the ischemic area of the cerebral cortex. ResultCompared with the sham group， the I/R group showed a significant increase in neurological deficit scores and infarct volume （P<0.01）， along with a higher apoptosis rate of cortical neurons and elevated mRNA and protein expression levels of NLRP3， GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05）. In contrast， the medium- and high-dose XXMT combined with EA treatment significantly reduced neurological deficit scores and infarct volume （P<0.01）， and decreased the apoptosis rate of cortical neurons as well as the mRNA and protein expression levels of NLRP3， GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05）. The improvement showed a dose-dependent relationship with XXMT. ConclusionThe combined use of XXMT and EA can exert neuroprotective effects by modulating the NLRP3/GSDMD/Caspase-1 signaling pathway， thereby reducing neurological deficits， minimizing brain infarct size， and improving cortical neuronal damage.

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.

ObjectiveTo evaluate the effect and safety of Jiuxin Pill （救心丸） on exercise tolerance and quality of life in patients with stable angina pectoris （SAP）. MethodsA randomised， double-blind， placebo-controlled， multicentre study design was used to enroll 170 patients of SAP from nine centres， which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan， and added Jiuxin Pill or placebo respectively， 2 pills （0.05 g） each time twicely for 28 days. The main outcomes were total exercise time （TED） in the exercise treadmill test and Seattle Angina Questionnaire （SAQ） scores including physical limitation （PL）， angina stability （AS）， angina frequency （AF）， treatment satisfaction （TS）， and disease perception （DP）. The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min （HRR1）， metabolic equivalents （METs）， maximum magnitude of ST-segment depression， and the Borg rating of perceived exertion scale， the average number of angina attacks per week， withdrawal and reduction rate of nitroglycerin， traditional Chinese medicine syndrome scores， incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment， day 28±2 in treatment period， and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set （FAS） and safety analysis set （SS）. Compared with the group before treatment and with the control group after treatment， the trial group had higher TED， HRR1， and METs， and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment （P＜0.01）. Compared with the group before treatment and with the control group after treatment and at follow-up， the total SAQ score and scores of AS， AF， TS and DP of the trial group after treatment and at follow-up elevated， while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced （P＜0.01）. There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups （P＞0.05）. Major adverse cardiovascular events occurred in 1 case （1/84， 1.19%） in the trial group and 1 case （1/85， 1.18%） in the control group， and the difference between groups was not statistically significant （P＞0.05）. A total of 3 cases of adverse events occurred in the trial group （3/84， 3.57%）， and a total of 6 cases of adverse events occurred in the control group （6/85， 7.06%）， and there was no statistically significant difference in the incidence of adverse events between groups （P＞0.05）. ConclusionIn the treatment of SAP， Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance， improve quality of life， and demonstrate great safety.

Objective To observe the value of clinical and CT radiomics features for predicting microsatellite instability-high(MSI-H)status of gastric cancer.Methods Totally 150 gastric cancer patients including 30 cases of MSI-H positive and 120 cases of MSI-H negative were enrolled and divided into training set(n=105)or validation set(n=45)at the ratio of 7∶3.Based on abdominal vein phase enhanced CT images,lesions radiomics features were extracted and screened,and radiomics scores(Radscore)was calculated.Clinical data and Radscores were compared between MSI-H positive and negative patients in training set and validation set.Based on clinical factors and Radscores being significant different between MSI-H positive and negative ones,clinical model,CT radiomics model and clinical-CT radiomics combination model were constructed,and their predictive value for MSI-H status of gastric cancer were observed.Results Significant differences of tumor location and Radscore were found between MSI-H positive and negative patients in both training and validation sets(all P＜0.05).The area under the curve(AUC)of clinical model,CT radiomics model and combination model for evaluating MSI-H status of gastric cancer in training set was 0.760,0.799 and 0.864,respectively,of that in validation set was 0.735,0.812 and 0.849,respectively.AUC of clinical-CT radiomics combination model was greater than that of the other 2 single models(all P＜0.05).Conclusion Clinical-CT radiomics combination model based on tumor location and Radscore could effectively predict MSI-H status of gastric cancer.

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.