Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity in vitro and in vivo. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells in vitro, among them 33a and 36b exhibited potent activity against HCT116 cells (IC₅₀ = 0.27 and 0.49 μmol/L, respectively). Both compounds 33a and 36b inhibited cell metastasis, arrested the cell cycle in the G₂/M phase, and induced apoptosis in vitro. Mechanistic studies revealed that 33a and 36b increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds 33a and 36b showed antitumor activity by suppressing the c-MYC pathway. c-MYC silencing assays indicated that c-MYC proteins participated in 33a-mediated anticancer activities in HCT116 cells. More importantly, compound 33a presented favorable pharmacokinetic properties in mice (T _1/2 = 6.8 h) and showed significant antitumor efficacy in vivo without obvious toxicity, showing promising potential for further clinical development.

Metabolic dysfunction-associated fatty liver disease (MAFLD), characterized by fatty acid overload, secondary chronic inflammation, and fibrosis, has become the most prevalent chronic liver disease globally. While no effective pharmacotherapy exists for MAFLD, mitigating inflammatory responses represents a promising approach to preventing the progression from steatosis to severe steatohepatitis. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which detects endogenous danger and stress signals, has emerged as a significant target for inflammatory disease treatment, as transcriptional inactivation of its components demonstrates the therapeutic potential for MAFLD. Natural products targeting NLRP3 inflammasome activation have shown promising efficacy in MAFLD therapy. This review synthesizes the current understanding of NLRP3 inflammasome activation and therapeutic targets for NLRP3 homeostasis. Additionally, natural products reported to inhibit NLRP3 inflammasome for MAFLD improvement are categorized according to their mechanisms of action. The review also addresses limitations and future directions regarding natural products targeting NLRP3 inflammasome in MAFLD treatment. Enhanced understanding of NLRP3 inflammasome activation mechanisms in MAFLD and the identification of novel natural products supported by mechanistic research will significantly advance MAFLD treatment.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Inflammasomes/metabolism* ; Biological Products/therapeutic use* ; Animals ; Fatty Liver/immunology*

OBJECTIVE To establish a method for simultan eous determination of 5 kinds of pentacyclic triterpenoids as 3-O- acetyl-pomolic acid in Chaenomeles speciosa ，and to analyze the difference in the contents of C. speciosa from different producing areas by different processing technologies . METHODS HPLC method was adopted . The determination was performed on COSMOSIL 5 C18-MS-Ⅱ column with mobile phase consisted of acetonitrile -0.005 mol/L ammonium dihydrogen phosphate solution （pH value adjusted to 6.5 with phosphoric acid ）（70∶30，V/V）at the flow rate of 1.0 mL/min. The column temperature was set at 30 ℃. The detection wavelength was set at 210 nm，and sample size was 20 μL. The contents of the other four pentacyclic triterpenoids were calculated according to quantitative analysis of multi -components by single -marker（QAMS）using oleanolic acid as internal reference . The results were compared with those determined by external standard method . The total content of oleanolic acid and ursolic acid ，the total content of 5 components in C. speciosa from different producing areas and different processing technologies were compared . RESULTS The linear range of 3-O-acetyl-pomolic acid ，betulinic acid ，oleanolic acid ，ursolic acid and 3-O-acetyl ursolic acid were 4.06-81.2，2.12-42.4，9.62-192.3，7.77-155.4，4.21-84.1 μg/mL，respectively（R2＞0.999）. RSDs of precision ，reproducibility and stability （24 h）tests were all lower than 3%. The average recoveries were 98.29%-101.38% （RSDs＜3%，n＝6）. The mass fraction of 3-O-acetyl-pomolic acid ，betulinic acid ，ursolic acid and 3-O-acetyl ursolic acid measured by QAMS w ere 0.023%-0.060%，0.044%-0.528%，0.101%-0.368%，0.067%-0.221%，respectively；the deviations from the results measured by external standard method were all within 8%. The total content of oleanolic acid and ursolic acid， the total content of 5 components in C. speciosa processed by fresh -cut technology from the same producing area were higher than those in C. speciosa processed by traditional technology ，and the total content of 5 components in C. speciosa from Chongqing Qianjiang were significantly higher than those from other producing areas （P＜0.05）. CONCLUSIONS QAMS method is established for the simultaneous determination of 3-O-acetyl-pomolic acid ，betulinic acid ，oleanolic acid ，ursolic acid and 3-O-acetyl ursolic acid in C. speciosa. Established method is simple ，rapid and accurate . The total content of 5 components in C. speciosa produced in Chongqing Qianjiang is higher ，and the total content of C. speciosa processed by fresh -cut technology from the same origin is higher than C. speciosa processed by traditional technology .

Objective:To explore the changes of bone mineral density (BMD) and type H vessel, which was recently identified as strongly positive for CD31 and Endomucin (CD31 hiEmcn hi) in long bone from ovariectomized (OVX) mice compared withSham group. Methods:C57BL/6Jwild-type mice were used for experiments and bone tissuewas collected. Eight-week-old female mice were randomly divided into bilateral ovariectomy (OVX) and a sham operation (Sham). The bilateral ovaries were exposed and removed in the OVX group. In the sham group, the ovaries were only exposed but left intact. After 4weeks, these mice were killed for experiment and the femurs were collected for Micro CT scanning in order to observe the changes of bone mineral density (BMD) and trabecular indexes, including bone volume (BV), total volume of interest (TV), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N). The fresh tibia of each mouse was fixed, decalcified, dehydrated and embedded for immunostaining. All experimental data were analyzed with t-test. Results:Mouse femora from two groups were dissected at 4 week time points, and the attached soft tissue was completely removed for Micro CT scanning. BMD in OVX is 0.11±0.01 g/cm 3 and 0.21±0.01 g/cm 3 in Sham, which indicated the BMD in OVX significantly decreased. The results showed significant difference between the groups ( P=0.001). The microarchitecture in trabecular bone changed. BV/TV in OVX is 11.52%±1.77% and 25.87%±1.31% in Sham, which indicated the BV/TV in OVX significantly decreased. The results showed significant difference between the groups ( P<0.05). Tb.N in OVX is 1.67±0.33/mm and 2.95±0.82/mm in Sham, which indicated the Tb.N in OVX slightly decreased. The results showed no significant difference between the groups ( P=0.066). Tb.Th in OVX is 0.06±0.01 mm and 0.07±0.01 mm in Sham, which indicated the Tb.Th in OVX significantly thinned. The results showed significant difference between the groups ( P=0.021). Tb.Sp in OVX is 0.29±0.15 mm and 0.19±0.01 mm in Sham, which indicated the Tb.Sp in OVX significantly increased. The results showed significant difference between the groups ( P<0.05). In the groups BMD decreased and trabecular microstructure was broken. Both BMD and trabecular indexes (BV/TV, Tb. Th, Tb. Sp) showed significant changes in OVX group compared with Sham ( P<0.05) except Tb.N. We next examined the expression of CD31 and EMCN via immunostaining in order to observe the changes of type H vessel.By immunostaining, the percentage of HV/TV in OVX group was 9.14%±0.99% and 29.33%±1.22% in the sham-operated mice. Dramatically decreased type H vessels in the metaphysis of OVX mice were observed compared with that of Sham control mice. The results showed significant difference between the groups ( P<0.05). Conclusion:In this study, ovariectomized mice, a widely used model for postmenopausal osteoporosis, exhibited significantly reduced type H vessels accompanied by reduced BMD, which indicatedtype H vessel involved in the occurrence of postmenopausal osteoporosis.

Objective: To analyze the chemical constituents of Morchella esculenta, and to determine the main activeingredient of it, so as to better control the quality of Morchella esculenta and promote the development and utilization of Morchella. Methods: The compounds were extracted and percolated by ethanol. The samples were separated using silicagel and identified by13C-NMR data. HPLC was used to assay the contents of 4-Hydroxybenzyl alcohol. Results: A totalof 5 compounds were isolated and their structures were identified as 11, 15, 19-trimethyl-5, 9-eicosadienoic acid, cis-13-Docosenoic acid&Erucic acid, 4-Hydroxybenzyl alcohol, Ergosta-5, 7, 22-triene-3β-ol and Mannitol. Conclusion: 4-Hydroxybenzyl alcohol was first isolated from the Morchella esculenta fruiting body, and HPLC method for thedetermination of 4-Hydroxybenzyl alcohol was established. The content of 4-Hydroxybenzyl alcohol were no less than0.40％. The determination method can be used for quality control of Morchella esculenta.

ObjectiveTo study the associations of Val66Met functional polymorphism in brain-derived neurotrophic factor (BDNF)with creativity and personality traits in a healthy college student population.MethodThe creativity performance and personality traits of the 830 healthy college students (272 males and 558females) were assessed with Williams Creativity Scale (CAP) and adult Eysenek Personality Questionnaire (EPQ),then study was performed on the association Val66Met in BDNF with creativity and personality traits.ResultsThe results indicated that Val66Met was significantly associated with the curiosity of CAP (F=0.519,P=0.036).The numbers of Val allele showed a positive correlation to the performance of curiosity.Val66Val genotype individuals had the best performance (31.924 ± 4.010 ) while the Met66Met ones showed the worst performante(30.889 ± 3.478).However,the association of Val66Met with the personality traits of EPQ was uot significant in the study (P＞ 0.05).Furthermore,there was no a significant effect of the interaction between the genetic variant and Extraversion/Introversion on the curiosity of CAP (P =0.747 ).ConclusionThe present study suggests that Val66Met in BDNF contributes to creativity,but not to personality traits in the population.

Objective To evaluate the therapeutic effects of stereotactic conformal radiotherapy (SCRT) on 30 cases of thalamic and brainstem tumors. Methods During the period from October 1997 to April 2002, 30 patients, 19 male and 11 female, with an age range from 13 to 68 years (an average of 37 years) suffering from thalamic and brainstem tumors, were treated in our institute. The size of the tumors ranged from 3.5 cm 3 to 73.0 cm 3 with an average of 16.5 cm 3. Eight cases were treated with SCRT after regular radiotherapy, 7 cases were treated with SCRT after surgical resection of the tumor and 15 cases were treated with SCRT only. Results The clinical symptoms of all the patients disappeared thoroughly. Their KPS was significantly improved (P