OBJECTIVE To conduct a comprehensive clinical evaluation of four nucleoside （acid） analogues that have been approved and marketed in China， such as entecavir， tenofovir disoproxil fumarate， tenofovir alafenamide fumarate， and tenofovir amibufenamide. METHODS According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs （2021 edition， trial implementation）， a comprehensive search was conducted across databases including CNKI， Wanfang Data， VIP， PubMed， the Cochrane Library， Embase， as well as relevant official websites. Drug package inserts， guidelines， consensus statements， and relevant literature for the four drugs were collected and subjected to a comprehensive evaluation across six dimensions： safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility. RESULTS The scores for entecavir in terms of safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility-along with its comprehensive score-were 13， 14， 13， 10， 18， and 6， totaling 74 points. For tenofovir disoproxil fumarate， the respective scores were 13， 17， 18， 8， 18， and 7， totaling 81 points. For tenofovir alafenamide fumarate， the scores were 14， 20， 12， 8， 18， and 5， totaling 77 points. Finally， for tenofovir amibufenamide， the scores were 10.5， 17， 10， 6， 15， and 4， totaling 62.5 points. CONCLUSIONS Tenofovir disoproxil fumarate， with the highest score， is recommended as the first-line option， suitable for adults， children， and pregnant women. However， caution is warranted for potential renal impairment. Tenofovir alafenamide fumarate is recommended as a second-line alternative， particularly for individuals at high risk for bone and renal damage. Entecavir has a score similar to tenofovir alafenamide fumarate but requires dosing on an empty stomach and dose adjustment based on renal function of patients. Tenofovir amibufenamide received the lowest score and is considered a weak recommendation. The clinical application of these nucleoside （acid） analogues should be individualized based on the patient’s age， physiological status， and risk factors.

Objective To investigate the risk factors for the occurrence of metabolic dysfunction-associated steatotic liver disease(MASLD)in lean individuals and construct a risk prediction model.Methods Based on the National Health and Nutrition Examination Survey(NHANES)database in the United States(from January 2017 to March 2020),1 123 adult individuals were included in this study.Then the participants were randomly divided into a training set(n=561)and a validation set(n=562)through simple random sampling.Data on their demographics,anthropometrics,lifestyle,underlying diseases,and laboratory test results were collected.LASSO regression analysis was used to screen potential variables in the training set,and multivariate logistic regression was employed to identify independent risk factors for lean MASLD.Based on these risk factors,a prediction model for lean MASLD was constructed(LMPM).To evaluate the clinical value of the LMPM,it was compared with two commonly used prediction models for non-alcoholic fatty liver disease,the fatty liver index(FLI)and the hepatic steatosis index(HSI).The performance of the model was evaluated and internally validated using the area under the receiver operating characteristic curve(AUC),net reclassification index(NRI),integrated discrimination improvement(IDI),calibration curve,decision curve,and clinical impact curve.Results Age,waist circumference,and triglycerides(TG)were identified as independent risk factors for the development of MASLD in lean individuals.The LMPM,constructed based on these indicators,demonstrated good discriminative ability in both the training and validation sets,with AUC values of 0.86(95%CI:0.82～0.89)and 0.81(95%CI:0.77～0.85),respectively,which were significantly better than those of FLI[training set:AUC=0.83(95%CI:0.79～0.87);validation set:AUC=0.74(95%CI:0.70～0.79)]and HSI[training set:AUC=0.71(95%CI:0.66～0.76);validation set:AUC=0.71(95%CI:0.65～0.76)].Compared with FLI and HSI,the LMPM showed improvements in NRI and IDI in both the training and validation sets.The calibration curve demonstrated its high accuracy,and both the decision curve analysis and the clinical impact curve analysis indicated that the LMPM provided greater clinical benefits.Conclusion Age,waist circumference,and TG are independent risk factors for lean MASLD.Based on these factors,a prediction model,named LMPM,is developed to assess the risk of MASLD in lean individuals,which exhibits good predictive performance and has certain guiding significance for the timely identification of high-risk populations.

Objective To analyze the risk factors of fluconazole resistance in Candida tropicalis(C.tropicalis)urinary tract infection(UTI),and evaluate the efficacy of different treatment regimens.Methods Patients with C.tropicalis UTI at Xiangya Hospital of Central South University from January 2021 to December 2023 were in-cluded for single center retrospective study.The minimum inhibitory concentration(MIC)of fluconazole was deter-mined by microbroth dilution.Patients were divided into a fluconazole-resistant group and a fluconazole-sensitive group based on fluconazole resistance.Risk factors for fluconazole resistance were analyzed based on clinical data,and therapeutic efficacy in patients in fluconazole-resistant group was analyzed.Results A total of 198 patients were included in the study.133(67.2％)C.tropicalis strains were detected to be sensitive to fluconazole,while 65(32.8％)strains were resistant,and 63.1％(n=41)had MIC values ≥128 μg/mL.Compared with fluconazole-sensitive group,fluconazole-resistant group had a higher proportion of pulmonary infection(P=0.019).Pulmonary infection(OR=3.282)was a risk factor for fluconazole resistance in C.tropicalis UTI,while urinary system ob-struction(OR=0.269)was a protective factor for fluconazole resistance in C.tropicalis UTI.There was no statis-tically significant difference in the usage rate of different antimicrobial agent types between the two groups(all P＞0.05).The therapeutic efficacy analysis showed that the effective rates of treatment with fluconazole dosage regi-mens of ≤200 mg/d,≥400 mg/d,and fluconazole monotherapy against fluconazole-resistant strains were 66.7％(6/9),83.3％(5/6),and 100％(6/6),respectively.For patients treated with monotherapy using other drugs or with multidrug sequential treatment regimens,the treatment effective rate was 60.0％(3/5).The proportion of pa-tients in the effective treatment group who removed their urinary catheters after detecting C.tropicalis was higher than that in the ineffective treatment group(P＜0.001).Conclusion The fluconazole resistance of C.tropicalis is related to urinary tract obstruction and concurrent pulmonary infection.When treating UTI caused by fluconazole-resistant strains,the catheter should be removed as early as possible.In addition to increasing the dosage of flucon-azole,other antifungal drugs such as flucytosine alone or sequential treatment with multiple drugs can also be con-sidered.

Cold tumors have a poor response to tumor immunotherapy due to low immune cell infiltration and the ability to evade immune attacks. Converting cold tumors into hot tumors can enhance the clinical effectiveness of anti-tumor immunotherapy. High-intensity focused ultrasound (HIFU) as a non-invasive treatment can damage tumors through mechanical effects, but there is a lack of research on its cytotoxic mechanisms at the cellular level and its role in inducing anti-immune responses. In this study, the role of HIFU in triggering tumor ferroptosis by disrupting the GSH/GSSG balance through mechanochemical action and the associated anti-tumor immune priming effect were investigated. The use of a nano-enhancer loaded with PFOB combined with HIFU could enhance ferroptosis in triple-negative breast cancer at a specific stage of tumor growth (UTGR = 0) while promoting the conversion of a cold tumor into a hot tumor, thereby improving the immune response. Overall, this provides valuable guidance for the clinical application of HIFU in tumor immunotherapy.

In the strategic context of "healthy China"， the concept of "medicine and food homology"， rooted in the culture of traditional Chinese medicine （TCM）， has received unprecedented attention. In response to population aging in China， the health of the elderly has become the focus of public health attention， and proactive health is the key to healthy aging. From the perspective of the application of medicinal and edible materials in proactive health and technological responses to population aging for the first time， this paper firstly provided a systematic overview of medicinal and edible materials and the policies related to proactive health. Second， it summarized the situation of modern technology that accelerates the research and development of medicinal and edible products， as well as the current situation of various modern biotechnologies that reveal the mechanism of action of medicinal and edible materials. Third， it discussed the application scenarios of medicinal and edible materials in proactive health and technological responses to population aging， as well as the future research and development of medicinal and edible materials. By exploring in depth the unique value and importance of medicinal and edible materials， the paper lays a theoretical foundation for improving the health care capabilities of TCM and contributes new strategies derived from TCM to healthy aging.

Anthoceros angustus Steph. is rich in phenolic acids such as rosmarinic acid (RA). Phenylalanine ammonia-lyase (PAL) is an entry enzyme in the phenylpropanoid pathway of plants, playing an important role in the biosynthesis of RA. To investigate the important role of PAL in rosmarinic acid synthesis, two PAL genes (designated as AanPAL1 and AanPAL2) were cloned from A. angustus, encoding 755 and 753 amino acid residues, respectively. The AanPAL deduced amino acid sequences contain the conserved domains of PAL and the core active amino acid residues Ala-Ser-Gly. The phylogenetic analysis indicated that AanPAL1 and AanPAL2 were clustered with PALs from bryophytes and ferns and had the shortest evolutionary distance with the PALs from Physcomitrella patens. Quantitative real-time PCR results showed that the expression of AanPAL1 and AanPAL2 was induced by exogenous methyl jasmonate (MeJA). HPLC results showed that the MeJA treatment significantly increased the accumulation of RA. AanPAL1 and AanPAL2 were expressed in Escherichia coli and purified by histidine-tag affinity chromatography. The recombinant proteins catalyzed the conversion of L-phenylalanine to generate trans-cinnamic acid with high efficiency, with the best performance at 50 ℃ and pH 8.0. The K_m and k_cat of AanPAL1 were 0.062 mmol/L and 4.35 s^-1, and those of AanPAL2 were 0.198 mmol/L and 14.48 s^-1, respectively. The specific activities of AanPAL1 and AanPAL2 were 2.61 U/mg and 8.76 U/mg, respectively. The two enzymes had relatively poor thermostability but good pH stability. The high activity of AanPAL2 was further confirmed via whole-cell catalysis with recombinant E. coli, which could convert 1 g/L L-phenylalanine into trans-cinnamic acid with a yield of 100% within 10 h. These results give insights into the regulatory role of AanPAL in the biosynthesis of RA in A. angustus and provide candidate enzymes for the biosynthesis of cinnamic acid.
Phenylalanine Ammonia-Lyase/metabolism* ; Cloning, Molecular ; Cinnamates/metabolism* ; Recombinant Proteins/metabolism* ; Rosmarinic Acid ; Depsides/metabolism* ; Escherichia coli/metabolism* ; Amino Acid Sequence ; Plant Proteins/metabolism* ; Phylogeny ; Acetates/pharmacology* ; Cyclopentanes ; Oxylipins

As the location with special public health environments,funeral parlors are of paramount importance in the prevention and control of infectious diseases as well as disinfection practices.This paper analyzes the unique hy-gienic characteristics of funeral parlors,summarizes relevant laws,regulations,standards,and literatures in funeral parlors at home and abroad,and elaborates the problems relevant to infection prevention and control in funeral par-lors from perspectives of body disposal risks,microbial contamination characteristics in funeral parlors,and the current status of staff's knowledge on infectious diseases.It aims to enhance the professional prevention and control capabilities of funeral service personnel and management personnel,ensure the health and safety of service recipients and staff,optimize service quality,provide theoretical basis and practical guidance for forming a sound infectious disease prevention and control system for funeral service institutions,and clarify research directions for the preven-tion and control of infectious diseases in funeral parlors in the future.

AIM:To establish methods for the isolation,identification,primary culture and evaluation of gas-tric smooth muscle cells(GSMC)from rat and mouse.METHODS:Thirty SD rats and thirty C57BL/6 mice were random-ly assigned into three groups,with 10 rats or mice in each group.Three parallel experiments were conducted to isolate pri-mary GSMC under aseptic conditions.The isolated cells were identified through morphological observation,immunofluo-rescence and Western blot.Flow cytometry was employed to analyze the purity of the cells.Additionally,trypan blue ex-clusion test was utilized to evaluate the viability of the cells after resuscitation.RESULTS:Isolated rat and mouse GSMC exhibited a fusiform or polygonal morphology.Immunofluorescence and Western blot results demonstrated the expression of α-smooth muscle actin(α-SMA).Flow cytometry showed that the positive expression rate of α-SMA was 99.6%in rat GSMC and 97.4%in mouse GSMC.Moreover,the viability rates of rat and mouse GSMC after cryopreservation were found to be greater than 97%.CONCLUSION:A stable and reliable method for the isolation,culture and evaluation of primary GSMC from rat and mouse has been established.

Objective To analyze the risk factors of fluconazole resistance in Candida tropicalis(C.tropicalis)urinary tract infection(UTI),and evaluate the efficacy of different treatment regimens.Methods Patients with C.tropicalis UTI at Xiangya Hospital of Central South University from January 2021 to December 2023 were in-cluded for single center retrospective study.The minimum inhibitory concentration(MIC)of fluconazole was deter-mined by microbroth dilution.Patients were divided into a fluconazole-resistant group and a fluconazole-sensitive group based on fluconazole resistance.Risk factors for fluconazole resistance were analyzed based on clinical data,and therapeutic efficacy in patients in fluconazole-resistant group was analyzed.Results A total of 198 patients were included in the study.133(67.2％)C.tropicalis strains were detected to be sensitive to fluconazole,while 65(32.8％)strains were resistant,and 63.1％(n=41)had MIC values ≥128 μg/mL.Compared with fluconazole-sensitive group,fluconazole-resistant group had a higher proportion of pulmonary infection(P=0.019).Pulmonary infection(OR=3.282)was a risk factor for fluconazole resistance in C.tropicalis UTI,while urinary system ob-struction(OR=0.269)was a protective factor for fluconazole resistance in C.tropicalis UTI.There was no statis-tically significant difference in the usage rate of different antimicrobial agent types between the two groups(all P＞0.05).The therapeutic efficacy analysis showed that the effective rates of treatment with fluconazole dosage regi-mens of ≤200 mg/d,≥400 mg/d,and fluconazole monotherapy against fluconazole-resistant strains were 66.7％(6/9),83.3％(5/6),and 100％(6/6),respectively.For patients treated with monotherapy using other drugs or with multidrug sequential treatment regimens,the treatment effective rate was 60.0％(3/5).The proportion of pa-tients in the effective treatment group who removed their urinary catheters after detecting C.tropicalis was higher than that in the ineffective treatment group(P＜0.001).Conclusion The fluconazole resistance of C.tropicalis is related to urinary tract obstruction and concurrent pulmonary infection.When treating UTI caused by fluconazole-resistant strains,the catheter should be removed as early as possible.In addition to increasing the dosage of flucon-azole,other antifungal drugs such as flucytosine alone or sequential treatment with multiple drugs can also be con-sidered.

As the location with special public health environments,funeral parlors are of paramount importance in the prevention and control of infectious diseases as well as disinfection practices.This paper analyzes the unique hy-gienic characteristics of funeral parlors,summarizes relevant laws,regulations,standards,and literatures in funeral parlors at home and abroad,and elaborates the problems relevant to infection prevention and control in funeral par-lors from perspectives of body disposal risks,microbial contamination characteristics in funeral parlors,and the current status of staff's knowledge on infectious diseases.It aims to enhance the professional prevention and control capabilities of funeral service personnel and management personnel,ensure the health and safety of service recipients and staff,optimize service quality,provide theoretical basis and practical guidance for forming a sound infectious disease prevention and control system for funeral service institutions,and clarify research directions for the preven-tion and control of infectious diseases in funeral parlors in the future.