AIM To investigate the renal protective effects of Shiwei Ruxiang Powder on gouty nephritis in rats based on mitophagy.METHODS Rats were randomly divided into the blank group,the model group,the low-dose,medium-dose,and high-dose Shiwei Ruxiang Powder groups(200,400,800 mg/kg)and allopurinol group(10 mg/kg).The rat model of gouty nephropathy was established by gavage of potassium oxyzinate(750 mg/kg)and uric acid(300 mg/kg).The rats had their levels of UA,SCr,BUN,XOD,SOD,MDA,ROS measured by automatic biochemical analyzer,ELISA and chemical fluorescence method;their renal pathological changes observed by HE staining;their apoptosis of renal tissue cells observed by TUNEL staining;and their mRNA and protein expressions of IL-1β,TNF-α,Bax,Bcl-2,caspase-3,caspase-9,PINK1,Parkin and LC3-Ⅱ detected by RT-qPCR and Western blot.RESULTS Compared with the model group,Shiwei Ruxiang Powder groups displayed dose-dependently decreased serum levels of UA,BUN and SCr,renal deposition of urate crystal and apoptosis(P<0.05);decreased renal levels of ROS and inflammatory factors IL-1β and TNF-α(P<0.05);and increased renal expressions of mitochondrial autophagy-related proteins PINK1,Parkin and LC3-Ⅱ(P<0.01).CONCLUSION Shiwei Ruxiang Powder may relieve gouty kidney injury in rats by reducing the uric acid level,the renal oxidative stress and inflammatory response,and activating mitophagy pathway as well.

Objective To analyze the literature on artificial intelligence in forensic research from 2012 to 2022 in the Web of Science Core Collection Database,to explore research hotspots and developmen-tal trends.Methods A total of 736 articles on artificial intelligence in forensic medicine in the Web of Science Core Collection Database from 2012 to 2022 were visualized and analyzed through the litera-ture measuring tool CiteSpace.The authors,institution,country(region),title,journal,keywords,cited references and other information of relevant literatures were analyzed.Results A total of 736 articles published in 220 journals by 355 authors from 289 institutions in 69 countries(regions)were identi-fied,with the number of articles published showing an increasing trend year by year.Among them,the United States had the highest number of publications and China ranked the second.Academy of Forensic Science had the highest number of publications among the institutions.Forensic Science Inter-national,Journal of Forensic Sciences,International Journal of Legal Medicine ranked high in publica-tion and citation frequency.Through the analysis of keywords,it was found that the research hotspots of artificial intelligence in the forensic field mainly focused on the use of artificial intelligence technol-ogy for sex and age estimation,cause of death analysis,postmortem interval estimation,individual identification and so on.Conclusion It is necessary to pay attention to international and institutional cooperation and to strengthen the cross-disciplinary research.Exploring the combination of advanced ar-tificial intelligence technologies with forensic research will be a hotspot and direction for future re-search.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective:To analyze the correlation between serum calcium levels and the prognosis of survival and renal recovery in patients with acute kidney injury (AKI) accompanied by hypercalcemia.Methods:This retrospective study analyzed the clinical data of patients with AKI accompanied by hypercalcemia admitted to Shanghai General Hospital from December 2015 to August 2022. There were 157 patients included in the study. The observation endpoint was set at discharge, focusing on the patients' survival and renal recovery during this period. Based on their status at discharge, patients were divided into a survival group (116 cases) and a death group (41 cases); and among the survivors, into a renal recovery group (63 cases) and a non-recovery group (53 cases). Continuous variables conforming to normal distribution were expressed as xˉ± s, and the mean comparison between the two groups was performed using an independent sample t-test. Continuous variables not conforming to normal distribution were represented by median (interquartile range) and compared between groups using the Mann-Whitney U test. Categorical variables were expressed as frequency (percentage), and comparisons were made using the chi-squared (χ 2) test or Fisher's exact test, as applicable. The correlation between serum calcium levels and patient outcomes was analyzed using univariate and multivariate Logistic regression. Results:The average age of the study subjects was (68.37±16.28) years, with 97 males (61.78%). The ages in the survival and death groups were (65.39±16.13) years and (76.80±13.67) years, respectively, with 66 males in the survival group and 31 in the death group. The history of malignancy (excluding multiple myeloma) was 37 cases and 23 cases, respectively, and serum albumin levels were (35.41±6.84) g/L and (30.82±5.75) g/L, respectively. Significant Statistical differences were observed in age, gender, history of malignancy (excluding multiple myeloma), and serum albumin were found between the survival and death groups (statistical values: t=4.04, χ 2=4.49, χ 2=7.51, t=3.85; all P<0.05). AIK 1 stage were 33.33%(21/63) and 64.15%(34/53), 2 stage were 36.51%(23/63) and 24.53%(13/34), 3 stage were 30.16%(23/63) and 11.32%(6/34) in the renal recovery and non-recovery groupsrespectively. Serum calcium at discharge in the renal recovery and non-recovery groups were (2.50±0.38) mmol/L and (2.70±0.58) mmol/L, respectively, with mean serum calcium levels of (2.60±0.29) mmol/L and (2.78±0.39) mmol/L, and lowest serum calcium levels of (2.28±0.36) mmol/L and (2.50±0.51) mmol/L, respectively. BNP levels were 118 (64, 283) ng/L and 248 (69, 1 383) ng/L, respectively. Significant differences in AKI stage, serum calcium at discharge, mean serum calcium, lowest serum calcium, and BNP were observed between the two groups (statistical values: χ 2=11.84, t=2.26, t=2.75, t=2.73, U=2.62, all P<0.05). Multivariate logistic regression analysis showed that age ( OR=1.062, 95% CI 1.027-1.098, P<0.001), history of malignancy (excluding multiple myeloma) ( OR=3.811, 95% CI 1.623-8.951, P=0.002), and serum albumin ( OR=0.889, 95% CI 0.829-0.953, P=0.001) were independent risk factors for in-hospital mortality of patients; severity of AKI(AKI2 OR=2.984, 95% CI 1.281-6.954, P=0.011, AKI3 OR=5.280, 95% CI 1.863-14.963, P=0.002) and serum calcium level at discharge ( OR=0.813, 95% CI 0.666-0.992, P=0.041) were independent risk factors affecting early renal recovery of patients. Conclusion:Serum calcium level is not associated with the risk of in-hospital mortality in patients with AKI accompanied by hypercalcemia but is related to the prognosis of early renal recovery. Proactively managing serum calcium, along with treatment of the primary malignancy and correction of hypoalbuminemia can help improve the prognosis of these patients.

Liposome was used as carrier to carry triptolide and ginsenoside Rg3 in the treatment of pancreatic cancer tumor mice. The effects of liposome on the levels of CD4⁺ and CD8⁺ microenvironmental immune factors of pancreatic cancer tumor were investigated, and the tumor inhibitory effect and safety were evaluated. In this study, Pan02 cells were used to construct a tumor-bearing C57BL/6 mouse model. After 14 days of treatment, the changes in tumor volume and body weight of tumor-bearing mice were observed. The results showed that the high and low doses of liposome had significant therapeutic effect on tumor volume in the model group (P < 0.01), and the tumor inhibition rate of high doses of liposome was significantly increased compared with triptolide group (P < 0.05). Immunohistochemistry showed that compared with the model group, the tumor inhibition rate of liposome was significantly increased. The high-dose liposome group can up-regulate the ratio of immune factor CD4⁺/CD8⁺, inhibit the expression of tumor proliferation factor and promote the expression of tumor apoptosis factor, and has a high safety after pathological hematoxylin and eosin staining of liver, spleen, lung and kidney and serum factor detection. Animal welfare and experimental procedures are in accordance with the regulations of the Experimental Animal Ethics Committee of Henan University of Chinese Medicine (approval No.: DWLL202103173). This study provides a new idea for the exploration of immunotherapy for pancreatic cancer.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Char syndrome is a rare autosomal dominant genetic disorder characterized by patent ductus arteriosus, facial dysmorphism, and dysplasia of fingers/toes. It may also be associated with multiple papillae, dental dysplasia, and sleep disorders. TFAP2B has proven to be a pathogenic gene for neural crest derivation and development, and several variants of this gene have been identified. Bone morphogenetic protein signaling plays an important role in embryonic development by participating in limb growth and patterning, and regulation of neural crest cell development. TFAP2B is an upstream regulatory gene for bone morphogenetic proteins 2 and 4. Variants of the TFAP2B gene may lead to abnormal proliferation of neural crest cells by affecting the expression of bone morphogenetic proteins, resulting in multiple organ dysplasia syndrome. In addition, TFAP2B variants may only lead to patent ductus arteriosus instead of typical Char syndrome.

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*

Objective:To analyze the effects of different plasma B-type natriuretic peptide (BNP) changes on worsening renal function (WRF) on 1-year all-cause mortality in patients with acute heart failure (AHF).Methods:The clinical data of 399 patients with AHF admitted to our hospital from January 2015 to December 2019 were retrospectively analyzed. According to the severity of WRF, the patients were divided into non-severe worsening renal function (nsWRF) group, severe worsening renal function (sWRF) group and non-WRF group. Plasma BNP decrease was defined as a reduction of B-type natriuretic peptide (BNP) at the time of discharge by ≥30% compared with the time of admission.Demographic characteristics and medical history, clinical data at admission, during hospitalization and at discharge, and survival status 1 year after discharge were collected. The measurement data presented in the form of normal distribution are as follows: single factor analysis of variance is used for comparison between groups, and LSD- t test is used for comparison between pairs; The Kruskal Wallis rank sum test was used for the multi group comparison of non normal distribution measurement data, and Wilcoxon rank sum test was used for the pairwise comparison. The comparison of counting data between groups was conducted using χ 2 test. Survival analysis was conducted using the Kaplan Meier method and Log rank test, and the Cox proportional risk regression model was used to analyze the influencing factors of 1-year all-cause mortality in patients. Results:399 cases of AHF were divided into nsWRF group with 68 cases, sWRF group with 82 cases, and nWRF group with 249 cases. 86 cases (21.5%) died within 1 year after discharge. The one-year mortality rate of the sWRF group was higher than that of the nWRF group and nsWRF group [42.7% (35/82) vs 16.1% (40/249), 16.2% (11/68)], and the differences were statistically significant (The χ 2 values were 24.94 and 12.28 respectively, both P<0.001), while there was no statistically significant difference between the nWRF group and the nsWRF group (χ 2=0.00、 P=0.982). The 1-year mortality rate of the nWRF group and sWRF group with decreased BNP during hospitalization was lower than that of the non decreased BNP group [29.1% (6/55) vs 70.4% (19/27), 10.5% (17/162) vs 26.4% (23/87), The χ 2 values are 12.61 and 10.67 respectively, and the P values are <0.001 and 0.001, respectively. The occurrence of nsWRF during hospitalization did not increase the one-year all-cause mortality risk of AHF patients ( P=0.754), but the occurrence of sWRF increased the all-cause mortality risk of AHF patients (odds ratio=2.33, 95% confidence interval: 1.31-4.13, P=0.004). The decrease in BNP during hospitalization reduced the one-year all-cause mortality risk of AHF patients (odds ratio=0.36, 95% confidence interval: 0.23-0.55, P<0.001). Conclusions:NsWRF does not increase the one-year all-cause mortality risk of AHF patients, while sWRF increases the one-year all-cause mortality risk, and a decrease in BNP during hospitalization reduces the one-year all-cause mortality risk.

The successful development and application of mRNA COVID-19 vaccine fully illustrated the great potential and application prospect of mRNA technology in the field of biomedicine. Currently, many companies worldwide are developing drugs and vaccines based on mRNA technology for the prevention and treatment of various diseases. It can be foreseen that with the continuous launch of mRNA drugs, commercial GMP production capacity matching them is also urgent. The optimization of production processes, intelligent manufacturing and other risk control strategies, as well as the control of industrialization costs, will help improve the core competitiveness of mRNA innovative drug development. In view of this, this article will provide an overview of the global production process of mRNA drugs and the progress of related GMP production dynamics, sort out the key chain points of the mRNA industry chain, explore the construction of the mRNA pharmaceutical enterprise value chain and the formation of core competitiveness, and provide reference and reference for the research and development of innovative mRNA drugs and high-quality development in China.