Objective To investigate the predictive value of quantitative parameters of contrast-enhanced ultrasound (CEUS) in evaluating kidneys from donation after brain death (DBD) for the occurrence of delayed graft function (DGF) in recipients. Methods The clinical data of 134 DBD donors and 202 corresponding kidneys and recipients were retrospective analyzed. The recipients were divided into DGF group (n=39) and non-DGF group (n=163) according to the renal function after kidney transplantation. Conventional ultrasound, CEUS parameters, and clinical data were compared between the two groups. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off values for predicting DGF using CEUS parameters, clinical parameters, and their combination, based on the highest Youden index. The predictive ability of different parameters for DGF was evaluated. Results There were statistically significant differences in cortical peak intensity (PIc), medullary peak intensity (PIm), donor albumin (ALB), serum creatinine (Scr) after admission, and the Na⁺ concentration of recipients between the two groups (all P<0.05). The area under the curve (AUC) for predicting DGF using the combination of CEUS parameters PIc and PIm was 0.711, with an optimal cut-off value of 0.193 and a Youden index of 0.382. The AUC for predicting DGF using the combination of CEUS parameters PIc, PIm and clinical parameters was 0.808, with an optimal cut-off value of 0.191 and a Youden index of 0.517. The sensitivity and specificity were 0.769 and 0.613 for the former, and 0.769 and 0.748 for the latter, respectively. The AUC for predicting DGF using CEUS parameters PIc and PIm combined with clinical parameters was significantly higher than that using CEUS parameters PIc and PIm (P<0.05). Conclusions The CEUS quantitative parameters PIc and PIm have good predictive value in assessing kidneys from DBD donors for DGF in recipients, and the diagnostic efficacy is better when combined with clinical parameters.

Objective　To analyze the epidemiological characteristics and infection sources of six human Streptococcus suis infection outbreaks in Shenzhen in 2023, and to provide a reference for effective prevention and control of the epidemic. Methods　Field epidemiological methods were used to investigate the disease onset and medical consultation process, exposure history of household and farmer market pork stalls, and other relevant factors. Data on patient demographics, clinical profiles, epidemiological characteristics, and common exposure cases were collected. Blood, cerebrospinal fluid, and environmental samples were collected for pathogen detection and genotyping. Spatial-geographical analysis of infection characteristics was performed using the professional mapping software ArcMap. Results　In 2023, a total of six cases were reported in Shenzhen, all of which were severe hospitalized cases with no deaths. Among them, five cases were of the meningitis type, and one was of the common type. All patients improved and were discharged after treatment. All six cases were male, with a median age of 47.5 years, and all had a history of direct exposure to raw pork through hand-skin wounds. Two cases were engaged in raw pork sales, while four were non-occupationally exposed individuals. Of the six cases, four were identified as Streptococcus suis serotype 2, and two were serotype 14. The positive rate of raw pork and environmental samples was 8.45% (6/71). Field epidemiological investigation found these six outbreaks were mainly directed toward three slaughterhouses in Guangming District, Bao'an District, and Longgang District. However, different genetic typing results suggested sporadic cases. Conclusions　These six outbreaks in Shenzhen in 2023 were all sporadic individual cases, showing characteristics such as multiple-point sporadic occurrences, diversified case composition, and primarily meningitis-type clinical manifestations. Although the genetic typing of the samples varied, the epidemiological investigation indicated three slaughterhouses as potential sources, providing a scientific basis for source control. In infectious disease epidemic source tracing, gene sequencing combined with field epidemiological surveys is more conducive to determining the source of infection and the relationship between transmission.

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

This article reports a patient with hepatic coma who underwent artificial liver support therapy and liver transplantation successfully， and the patient recovered well in the later stage after active treatment. This article also discusses the timing of liver transplantation.

Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease therapy. Compared with chemical synthesis and extraction, the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants, and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal plants. Here, we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal plants. The strategies and methods mainly include genetic engineering, plant cell culture engineering, metabolic engineering, and synthetic biology based on multiple "OMICS" technologies, with paradigms for the biosynthesis of terpenoids and alkaloids. We also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products, exemplifying compounds such as vindoline (alkaloid), artemisinin and paclitaxel (terpenoids), to illustrate the power of biotechnology in medicinal plants.

BACKGROUND:It has been demonstrated that osteoclast activation plays an important role in skeletal system-related diseases.The mechanism of regulation of osteoclast activation by extracellular vesicles carrying non-coding RNA has not been fully elucidated. OBJECTIVE:To review and summarize relevant literature in and outside China,and to review the regulation of osteoclast activation by different non-coding RNAs in extracellular vesicles in different diseases,so as to provide a certain direction for subsequent research. METHODS:"Non-coding RNA,miRNA,lncRNA,circRNA,snoRNA,osteoclasts,extracellular vesicles,exosome,microparticle,apoptotic bodies"were used as search terms to search the databases of CNKI,WanFang,and VIP."Extracellular vesicles,exosome,microparticle,apoptotic bodies,non-coding RNA,miRNA,lncRNA,circRNA,snoRNA,osteoclast"were used as search terms to search PubMed.Finally,71 articles were included. RESULTS AND CONCLUSION:(1)The activation of osteoclasts is affected by many factors,among which the specific mechanism of non-coding RNA regulating osteoclast activation is not clear.(2)Extracellular vesicles can be secreted by osteoblasts,bone marrow mesenchymal stem cells,tumor cells and other cells.As a carrier of intercellular communication,extracellular vesicles can carry non-coding RNA to regulate osteoclast activation.(3)In the current studies on the regulation of osteoclast activation by extracellular vesicles carrying non-coding RNA,most of the diseases are osteoporosis,followed by tumor bone metastasis,and most types of non-coding RNA are miRNA.(4)There are relatively few studies on the regulation of extracellular vesicles carrying lncRNA and circRNA and snoRNA on osteoclast activation,and the regulatory mechanism is mainly ceRNA mechanism.(5)In conclusion,an in-depth study of the regulatory mechanism of extracellular vesicles carrying non-coding RNA on osteoclast activation is helpful to find key targets for the treatment of skeletal system-related diseases.

BACKGROUND:Compared with traditional two-dimensional culture,three-dimensional microtissue culture can show greater advantages.However,more favorable cultivation methods in three-dimensional culture still need to be further explored. OBJECTIVE:To evaluate the cell behavior of microtissue and its ability to promote cartilage formation under two three-dimensional culture methods. METHODS:Cartilage-derived microcarriers were prepared by chemical decellularization and tissue crushing.DNA quantification and nuclear staining were used to verify the success of decellularization,and histological staining was used to observe the matrix retention before and after decellularization.The microcarriers were characterized by scanning electron microscopy and CCK-8 assay.Cartilage-derived microtissues were constructed by combining cartilage-derived microcarriers with human adipose mesenchymal stem cells through three-dimensional static culture and three-dimensional dynamic culture methods.The cell viability and chondrogenic ability of the two groups of microtissues were detected by scanning electron microscopy,live and dead staining,and RT-qPCR. RESULTS AND CONCLUSION:(1)Cartilage-derived microcarriers were successfully prepared.Compared with before decellularization,the DNA content significantly decreased after decellularization(P<0.001).Scanning electron microscope observation showed that the surface of the microcarrier was surrounded by collagen,maintaining the characteristics of the natural extracellular matrix of cartilage cells.CCK-8 assay indicated that microcarriers had no cytotoxicity and could promote cell proliferation.(2)Scanning electron microscopy and live and dead staining results showed that compared with the three-dimensional static group,the three-dimensional dynamic group had a more extended morphology of microtissue cells,and extensive connections between cells and cells,between cells and matrix,and between matrix.(3)The results of RT-qPCR showed that the expressions of SOX9,proteoglycan,and type Ⅱ collagen in microtissues of both groups were increased at 7 or 14 days.The relative expression levels of each gene in the three-dimensional dynamic group were significantly higher than those in the three-dimensional static group at 14 days(P<0.05).At 21 days,the three-dimensional static group had significantly higher gene expression compared with the three-diomensional dynamic group(P<0.001).(4)The results showed that compared with three-dimensional static culture microtissue,three-dimensional dynamic culture microtissue could achieve higher expression of chondrogen-related genes in a shorter time,showing better cell viability and chondrogenic ability.

Objective:To investigate the effect of sleep on physical performance and the correlation between sleep quality and physical performance in the elderly.Methods:In this prospective multicenter case-control study, 472 elderly people aged 60-80 years were recruited from three regions in China, Beijing, Tianjin, and Hainan Province.Basic information of study participants was collected through face-to-face interviews, and physical performance of study participants was assessed by the time up and go(TUG)test on site, with 106 cases(22.5%)in the normal physical performance group and 366 cases(77.5%)in the abnormal group.The Pittsburgh Sleep Quality Index(PSQI)and the Epworth Sleepiness Scale(ESS)were applied to assess sleep quality of study subjects.Correlation analysis was performed to examine factors affecting subjects' physical performance.Results:Age, history of alcohol consumption, BMI, past medical history, the ESS score, daytime sleepiness, and some components of PSQI, such as sleep quality, sleep efficiency, sleep disturbances, use of sleeping drugs and daytime dysfunction, were influencing factors of the TUG score.Two components of PSQI, sleep duration and habitual sleep efficiency, and the ESS score were positively correlated with physical performance.Logistic regression analysis showed that risk factors for decreased physical performance in the elderly included increased age( OR=1.125, 95% CI: 1.083-1.168, P<0.01), history of alcohol consumption( OR=0.482, 95% CI: 0.384-0.605, P<0.001), abnormally high body mass index( OR=1.663, 95% CI: 1.340-2.063, P<0.01), hyperlipemia( OR=0.156, 95% CI: 0.077-0.318, P<0.01), digestive system diseases( OR=0.154, 95% CI: 0.044-0.532, P<0.01), use of sleeping drugs( OR=0.415, 95% CI: 0.202-0.854, P<0.05), daytime sleepiness( OR=4.234, 95% CI: 2.800-6.403, P<0.01), a high habitual sleep efficiency score of PSQI( OR=1.425, 95% CI: 1.214-1.672, P<0.01)and a high sleep disturbances score in PSQI( OR=3.356, 95% CI: 2.337-4.819, P<0.01). Conclusions:The incidence of physical performance decline is high in the elderly.There is a correlation between physical performance and sleep quality.

Objective To investigate the status of human papillomavirus(HPV)infection in women in Li-aocheng area,and to analyze the relationship between HPV genotypes and thin-prep cytologic test(TCT),so as to provide reference for the diagnosis,treatment and vaccination of cervical cancer in this area.Methods The relevant data of 4 968 women who underwent physical examination in the hospital from Januar-y 2020 to April 2023 were retrospectively analyzed.Cervical exfoliated cells were collected for TCT and HPV genotyping,and the distribution of HPV infection and genotype in women of different ages was analyzed.x2 test was used to compare the differences between groups,and multivariate Logistic regression was used to ana-lyze the influencing factors of different HPV types on cervical lesions.Results The overall HPV infection rate was 21.05％,and there was a significant difference in the overall infection rate among different age groups(x2=42.695,P＜0.001).The HPV infection rate of＞49-59 years old group was the highest(26.85％),followed by＞59 years old group.Among the different types of HPV infection,single infection accounted for the highest proportion(15.12％),followed by double infection(4.07％).The top five high-risk genotypes of HPV infection rate were HPV52,16,58,53,66,and HPV16,52,58 were the main high-risk genotypes in HPV single infection.TCT distribution of 1 046 HPV-positive cases:54.97％had no intraepithelial lesion or malig-nant lesion,29.64％atypical squamous cells of undetermined significance,2.58％atypical squamous cells could not exclude high-grade squamous intraepithelial lesion,11.47％low-grade squamous intraepithelial le-sion,and 1.34％high-grade squamous intraepithelial lesion.The infection rates of HPV16,58 and 66 were re-lated to the severity of cervical cytology(x2 trend=23.765,7.807,16.122,P＜0.05).Multivariate Logistic regression analysis showed that HPV16,18,31,33,35,39,51,52,53,56,58,59,66 genotypes were associated with cervical lesions.Conclusion The risk of HPV infection is high in women in this area,especially in mid-dle-aged and elderly women.High-risk HPV types 52,16 and 58 are the most common infection types in this area.HPV16 is closely related to the degree of cervical lesions.

Objective To explore the value of serum soluble transferrin receptor(sTFR)and urinary tryp-sin inhibitor(Bikunin)in assessing the short-term prognosis of patients with hepatitis B virus related acute on chronic live failure(HBV-ACLF).Methods A total of 103 patients with HBV-ACLF admitted to Weifang People's Hospital from January 2019 to December 2022 were collected as HBV-ACLF group,who were classi-fied into early stage group(n=46),middle stage group(n=34)and late stage group(n=23)according to the disease progression,and classified into good prognosis group(n=67)and poor prognosis group(n=36)according to clinical outcomes at 30 d after hospital admission.At the same time,65 patients with chronic hep-atitis B virus infection were selected as chronic hepatitis B group and 65 healthy volunteers were selected as control group were enrolled in the study.The clinical medical records of research objects were collected at the time of admission.Serum sTFR and Bikunin levels were detected by enzyme-linked immunosorbent assay.Spearman rank correlation analysis was performed to analyze the association between serum sTFR,Bikunin and disease progression.Multivariate Logistic regression analysis was performed to analyze factors affecting short-term poor prognosis of patients with HBV-ACLF.Receiver operating characteristic(ROC)curve was used to assess the predictive value of serum sTFR and Bikunin on prognosis.Results Serum sTFR and Bikun-in levels were lower in HBV-ACLF group and chronic hepatitis B group than those in control group,and those in HBV-ACLF group were lower than those in chronic hepatitis B group,and the differences were statistically significant(P＜0.05).Model for End-Stage Liver Disease(MELD)score was higher in HBV-ACLF group and chronic hepatitis B group than that in control group,and that in HBV-ACLF group was higher than that in chronic hepatitis B group,and the differences were statistically significant(P＜0.05).Compared with early stage group,serum sTFR and Bikunin levels decreased in middle stage group and late stage group,and those in late stage group were lower than those in middle stage group,and the differences were statistically significant(P＜0.05).MELD score increased in middle stage group and late stage group,and that in late stage group was higher than that in middle stage group,and the differences were statistically significant(P＜0.05).Serum sTFR and Bikunin in HBV-ACLF patients were associated with MELD score(r=-0.638,-0.592,P＜0.05),which were also associated with severity of disease(rs=-0.722,-0.671,P＜0.05).Elevated HB-sAg,elevated quantitative HBV DNA,middle and late stages of HBV-ACLF and elevated MELD score were independent risk factors for poor short-term prognosis in patients with HBV-ACLF(OR＞1,P＜0.05),while elevated serum sTFR and Bikunin were protective factors for poor short-term prognosis in patients with HBV-ACLF(OR＜1,P＜0.05).Serum sTFR and Bikunin both had some predictive value for poor short-term prog-nosis,and the predictive value of the combination was greater than that of single indicator(Z=2.139,2.165,P＜0.05).Conclusion Serum sTFR and Bikunin levels are decreased in patients with HBV-ACLF,which are associated with disease progression and short-term prognosis.Early combined detection of two indicators could predict the risk of poor prognosis in patients with HBV-ACLF at 30 d after hospital admission.