ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome, with implications for microbial pathogenesis and host defense. Among these, transfer RNA-derived small RNAs (tsRNAs) have garnered attention for their roles in modulating microbial behavior. However, the bacterial factors mediating tsRNA interaction and functionality remain poorly understood. In this study, using RNA affinity pull-down assay in combination with mass spectrometry, we identified a putative membrane-bound protein, annotated as P-type ATPase transporter (PtaT) in Fusobacterium nucleatum (Fn), which binds Fn-targeting tsRNAs in a sequence-specific manner. Through targeted mutagenesis and phenotypic characterization, we showed that in both the Fn type strain and a clinical tumor isolate, deletion of ptaT led to reduced tsRNA intake and enhanced resistance to tsRNA-induced growth inhibition. Global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences between Fn wild type and PtaT-deficient mutant, highlighting the functional significance of PtaT in purine and pyrimidine metabolism. Furthermore, AlphaFold 3 prediction provides evidence supporting the specific binding between PtaT and Fn-targeting tsRNA. By uncovering the first RNA-binding protein in Fn implicated in growth modulation through interactions with host-derived small RNAs (sRNAs), our study offers new insights into sRNA-mediated host-pathogen interplay within the context of microbiome-host interactions.
Fusobacterium nucleatum/growth & development* ; RNA-Binding Proteins/genetics* ; Bacterial Proteins/genetics* ; RNA, Bacterial/metabolism* ; Humans ; RNA, Transfer/metabolism*

A method for determination and targeted screening of diflorasone components in health products using ultra performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF/MS)was established.Four representative diflorasone and esters(diflorasone,diflorasone diacetate,diflorasone-17-propionate,and diflorasone-21-propionate)were selected to optimize the pretreatment conditions,and 10 mL of extraction solvent dosage,15 min of extraction time and 5 g of salting-out agent as the optimal conditions were selected by response surface methodology.The results showed that the four analytes exhibited good linearity within the concentration range of 2.0?100 μg/L with the chromatographic peak area,and the correlation coefficients(R2)were all greater than 0.9990,while the results of recovery and relative standard deviation could satisfy the requirements of determination.The common characteristic ions of diflorasone and esters werem/z121 andm/z335,and their specific structures were obtained by analyzing the cleavage pathway based on the optimized determination conditions.A targeted screening method for other esters of diflorasone based on characteristic ions guidance strategy was established.This method had many advantages such as high efficiency,high sensitivity and good reproducibility,and could be used for targeted screening of diflorasone and esters in health products.The developed characteristic ion guided strategy could be employed to construct mass spectral databases for various glucocorticoids,enabling comprehensive targeted screening across a broad range of compounds.

Background and objective Pulmonary sarcomatoid carcinoma(PSC)is a rare subtype of non-small cell lung cancer(NSCLC),which is featured by low incidence,high malignancy rate,robust aggressive behavior and inferior prognosis.To date,there is no standardized treatment.The aim of this study is to better understand and accumulate more clini-cal experience of the disease by summarizing the clinicopathological features,diagnosis methods,therapeutic regimen and prognostic factors of PSC.Methods A total of 39 patients with PSC who diagnosed and received treatment in Beijing Chest Hospital from December 2013 to December 2023 were retrospectively recruited,and information including demographic char-acteristics,clinicopathological features,tumor-node-metastasis(TNM)stage,diagnosis method and therapeutic regimen were carefully collected.Meanwhile,follow-up was conducted.Kaplan-Meier method was used to analyze the prognostic factors of the disease.Results The PSC patients in this study ranged in age from 45 to 76 years old,including 35 males and 4 females.There were no specific clinical manifestations of PSC at initial diagnosis.Among the 39 patients,20 underwent surgical resec-tion and 19 received palliative chemoradiation or symptomatic supportive treatment.The 1-year and 5-year survival rates were 61.90％and 35.20％respectively.Univariate analysis indicated that family history of carcinoma,primary tumor site,TNM stage,lymph node metastasis,distant metastasis,whether or not received surgical resection,surgical method,treatment regimens,tumor tissue programmed cell death ligand 1(PD-L1)expression＞1％and mesenchymal-epithelial transition factor(MET)pathway abnormalities were correlated with the overall survival(OS)of patients(P＜0.05).In the subsequent multivariate analysis,lymph node metastasis emerged as the only independent prognosticator in predicting inferior OS(P=0.037).Conclu-sion PSC is rarely seen in clinical practice and commonly occurs in elder men with smoking history.Tumor tissue PD-L1 ex-pression＞1％and MET abnormalities may predict inferior prognosis of PSC and lymph node metastasis was determined as the independent prognosticator of PSC.Surgical resection along with adjuvant medical treatment is the cornerstone for early and locally advanced patients,and the clinical utility of molecular targeting therapy and immunotherapy in PSC needs to be further investigated.

Objective This study aims to explore the research hotspots and trends of Polygoni Multiflori Radix(processed)and provide a reference for follow-up research by bibliometric visualization analysis.Methods Relevant Polygoni Multiflori Radix literatures were collected through databases such as PubMed,Web of Science and China National Knowledge Infrastructure.Use CiteSpace 6.1.R6 software to do bibliometric analysis on the number and years of articles,research fields,countries/regions,institutions,authors,keywords,co-citation references,and build visual maps.Results A total of 1 517 literatures(1 131 Chinese literatures and 386 English literatures)were searched through databases in this review.We therefore conducted a quantitative analysis of accessible literature published over the last 30 years found that a very modest upward trend in publication volume from Chinese and a notable increase in publication over the world.Among the author teams,there was some cooperation,and the author team with the most published papers cooperated more closely,such as XIAO Xiao-he and WANG Jia-bo's team.In particular reducing toxicity and increasing efficiency by processing,and the toxicity and the rationalusage of Polygoni Multiflori Radix were a main research direction for nearly ten years.Meanwhile,through the co-occurrence analysis of keywords,we constructed and visualized a keyword network to explore the hotspots and future directions of Polygoni Multiflori Radix.We clearly found that effective and toxic homologous components,molecular mechanisms and early warning surveillance of hepatotoxicity might be the next topics for Polygoni Multiflori Radix.Conclusion The research on the homologous chemical components of Polygoni Multiflori Radix(processed)has been very active.The research on the conversion relationship and mechanism of homologous components of Polygoni Multiflori Radix(processed)and the mechanism of hepatotoxicity will be the research focus and development trend in this field.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

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.

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype