The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction （枳壳甘草汤， ZGD） delays intervertebral disc degeneration （IDD） based on the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group， model group， low-dose ZGD group， high-dose ZGD group， and high-dose ZGD + inhibitor group， with 10 rats in each group. In the sham surgery group， the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle （depth approximately 2 mm） without damaging the intervertebral disc. In the other groups， rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling， rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/（kg·d） of the decoction via gastric gavage， respectively. The high-dose ZGD + inhibitor group was given 12.24 g/（kg·d） of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/（kg·d） of normal saline via gavage. The gavage was given once a day， and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention， the pathological changes of the tail intervertebral discs were observed using HE staining， Oil Red O-Green staining， and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus， and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway， including YAP， phosphorylated YAP （p-YAP）， phosphorylated MST1/2 （p-MST1/2）， phosphorylated TAZ （p-TAZ） and apoptosis-related proteins， such as Cleaved Caspase 3， P53， Bcl-2 and Bax. ResultsCompared with sham surgery group， the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan， Bcl-2， and YAP proteins in the nucleus pulposus decreased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate increased （P < 0.01）. Compared with the model group， the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan， Bcl-2， and YAP proteins increased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate decreased （P＜0.05 or P＜0.01）. The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group， with a decrease in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and an increase in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. Compared with the high-dose ZGD group， the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration， with an increase in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and a decrease in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus， maintaining the function of the Hippo-YAP/TAZ signaling pathway， and reducing apoptosis of nucleus pulposus cells.

Objective:To analyze the situation of rodents carrying Hantavirus and the genetic and evolutionary characteristics of the virus in Zibo city, Shandong province in 2022, and provide reference for the scientific prevention and control of hemorrhagic fever with renal syndrome (HFRS).Methods:Real-time quantitative PCR (RT-qPCR) was used to detect hantavirus (HV) nucleic acids in rodent lung tissues and identify HV genotypes. Each nucleic acid fragment was designed to amplify various gene fragments by segment, and the whole genome of Hantavirus was sequenced by second generation sequencing. Sequence assembly was performed using SeqMan 7.1.0.44, a subprogram of DNAStar. Sequence alignment and evolutionary analysis were conducted using MEGA 7.0 and BioEdit software.Results:A total of 270 host animals were captured in this survey. Among them, 13 rodent lung samples tested positive for Hantavirus, resulting in a virus-positive rate of 4.8%. The full-genome sequences of four hantavirus strains were successfully obtained, all identified as Seoul virus (SEOV) genotype. Four Hantavirus-positive samples showed high nucleotide sequence homology in the M gene and belonged to the SEOV S3 subtype. These strains exhibited high similarity with those from Hebei, Liaoning, and Beijing. The amino acid sequences of the nucleoprotein and glycoprotein immunogenic epitopes were identical to those of the vaccine strain Z37.Conclusions:This study successfully determined the full genome sequences of four hantavirus strains from Zibo city, Shandong province. The genotypes are primarily SEOV, with the subtype being S3. The homology of genes within the same subtype is high, with no significant variations observed. The alignment of immune epitopes in key proteins suggests that the current vaccine may provide protection against locally circulating strains, but further in-depth research is still required.

Objective:To understand the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Shandong province from 2010 to 2022, analyze the trends in morbidity and mortality, and provide a scientific basis for the prevention, control, diagnosis, and treatment of SFTS.Methods:The data on SFTS cases and deaths were retrospectively collected through the China Disease Control and Prevention Information System′s infectious disease surveillance system and the Shandong province all-cause mortality surveillance system. Descriptive epidemiological method was used for epidemiological analysis, and the Joinpoint regression model was applied to analyze trends in morbidity and mortality.Results:From 2010 to 2022, 6 714 SFTS cases were reported in Shandong, with an average crude incidence rate (CIR) and age-standardized incidence rate (ASIR) of 0.52/100 000 and 0.43/100 000, respectively. Among these, 1, 064 cases died within 30 days of onset, with an average crude mortality rate (CMR) and age-standardized mortality rate (ASMR) of 0.08/100, 000 and 0.06/100 000, respectively, and an average case fatality rate of 15.85%. The average incidence rates for males and females were 0.52/100 000 and 0.53/100 000, respectively, with no statistically significant difference ( P>0.05). The average annual mortality rate for males (0.09/100 000) was higher than that for females (0.08/100 000), and the average annual case fatality rate for males (17.21%) was higher than that for females (14.48%), with statistically significant differences ( P<0.05); 93.95% of the cases were over 45 years old, and 86.56% of the deaths were over 60 years old. Both cases and deaths were primarily among farmers, accounting for over 85% of the total. From 2010 to 2022, the incidence rate of SFTS in Shandong showed an overall upward trend, with an average annual percentage change (AAPC) in CIR of 23.58% and an AAPC in ASIR of 19.97%, P<0.05. The mortality rate of SFTS cases in Shandong from 2010 to 2022 showed a continuous and significant upward trend, with a CMR AAPC of 27.64% and an ASMR AAPC of 22.70%, P<0.05. SFTS incidence and mortality in Shandong exhibited clear seasonality, with high occurrence from May to October, primarily concentrated in the Jiaodong Peninsula and the hilly areas of central Shandong. The number of affected counties increased in a wave-like pattern, expanding from 6 in 2010 to 79 in 2021 for cases and from 2 in 2010 to 53 in 2022 for deaths. Conclusions:From 2010 to 2022, the incidence and mortality of SFTS in Shandong showed an upward and expanding trend, with a particularly heavy disease burden among middle-aged and elderly farmers.

Objective:To analyze the situation of rodents carrying Hantavirus and the genetic and evolutionary characteristics of the virus in Zibo city, Shandong province in 2022, and provide reference for the scientific prevention and control of hemorrhagic fever with renal syndrome (HFRS).Methods:Real-time quantitative PCR (RT-qPCR) was used to detect hantavirus (HV) nucleic acids in rodent lung tissues and identify HV genotypes. Each nucleic acid fragment was designed to amplify various gene fragments by segment, and the whole genome of Hantavirus was sequenced by second generation sequencing. Sequence assembly was performed using SeqMan 7.1.0.44, a subprogram of DNAStar. Sequence alignment and evolutionary analysis were conducted using MEGA 7.0 and BioEdit software.Results:A total of 270 host animals were captured in this survey. Among them, 13 rodent lung samples tested positive for Hantavirus, resulting in a virus-positive rate of 4.8%. The full-genome sequences of four hantavirus strains were successfully obtained, all identified as Seoul virus (SEOV) genotype. Four Hantavirus-positive samples showed high nucleotide sequence homology in the M gene and belonged to the SEOV S3 subtype. These strains exhibited high similarity with those from Hebei, Liaoning, and Beijing. The amino acid sequences of the nucleoprotein and glycoprotein immunogenic epitopes were identical to those of the vaccine strain Z37.Conclusions:This study successfully determined the full genome sequences of four hantavirus strains from Zibo city, Shandong province. The genotypes are primarily SEOV, with the subtype being S3. The homology of genes within the same subtype is high, with no significant variations observed. The alignment of immune epitopes in key proteins suggests that the current vaccine may provide protection against locally circulating strains, but further in-depth research is still required.

Objective:To understand the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Shandong province from 2010 to 2022, analyze the trends in morbidity and mortality, and provide a scientific basis for the prevention, control, diagnosis, and treatment of SFTS.Methods:The data on SFTS cases and deaths were retrospectively collected through the China Disease Control and Prevention Information System′s infectious disease surveillance system and the Shandong province all-cause mortality surveillance system. Descriptive epidemiological method was used for epidemiological analysis, and the Joinpoint regression model was applied to analyze trends in morbidity and mortality.Results:From 2010 to 2022, 6 714 SFTS cases were reported in Shandong, with an average crude incidence rate (CIR) and age-standardized incidence rate (ASIR) of 0.52/100 000 and 0.43/100 000, respectively. Among these, 1, 064 cases died within 30 days of onset, with an average crude mortality rate (CMR) and age-standardized mortality rate (ASMR) of 0.08/100, 000 and 0.06/100 000, respectively, and an average case fatality rate of 15.85%. The average incidence rates for males and females were 0.52/100 000 and 0.53/100 000, respectively, with no statistically significant difference ( P>0.05). The average annual mortality rate for males (0.09/100 000) was higher than that for females (0.08/100 000), and the average annual case fatality rate for males (17.21%) was higher than that for females (14.48%), with statistically significant differences ( P<0.05); 93.95% of the cases were over 45 years old, and 86.56% of the deaths were over 60 years old. Both cases and deaths were primarily among farmers, accounting for over 85% of the total. From 2010 to 2022, the incidence rate of SFTS in Shandong showed an overall upward trend, with an average annual percentage change (AAPC) in CIR of 23.58% and an AAPC in ASIR of 19.97%, P<0.05. The mortality rate of SFTS cases in Shandong from 2010 to 2022 showed a continuous and significant upward trend, with a CMR AAPC of 27.64% and an ASMR AAPC of 22.70%, P<0.05. SFTS incidence and mortality in Shandong exhibited clear seasonality, with high occurrence from May to October, primarily concentrated in the Jiaodong Peninsula and the hilly areas of central Shandong. The number of affected counties increased in a wave-like pattern, expanding from 6 in 2010 to 79 in 2021 for cases and from 2 in 2010 to 53 in 2022 for deaths. Conclusions:From 2010 to 2022, the incidence and mortality of SFTS in Shandong showed an upward and expanding trend, with a particularly heavy disease burden among middle-aged and elderly farmers.

Objective:To investigate the imaging quality of CBCT under different exposure parameters and the relationship between subjective and objective evaluation.Methods:CBCT scanners of 6 different suppliers[3D Accuitomo(Morita),i-mCAT(Kavo),5G(NewTom),Smart3D(Beijing Langshi),DCT Pro(Vatech),Vgi(NewTom)]were used to scan the spatial resolution models and head simulators under typical exposure conditions(different device with different tube voltage and current for exposure).The visibility of SedentexCT IQ phantom and anatomical structures generated by different CBCT scanners were compared.For objective evaluation,7 professional evaluators scored CBCT imaging qualities.For subjective evaluation,the resolution(LP/mm)of the images were com-pared among the devices.Results:No significant difference was found by 7 evaluators either intra or inter of the teams.By objective e-valuation,the score of NewTom 5G was 2,that of i-CAT was 5 and that of the others was 4.By subjective evaluation,the LP/mm of i-CAT was 1.8,that of Smart3D was 2.0 and that of the others was 1.0-1.7.The subjective evaluation of image quality obtained un-der different tube voltages and tube currents were significantly different.Conclusion:The subjective and objective evaluations of image quality are approximately consistent.The difference of the subjective image quality may be produced by the different tube voltage and current for exposure.

Objective:To analyze the surveillance data of population in rabies exposure and post-exposure prophylaxis (PEP) clinics in Shandong province from 2019 to 2023, explore risk factors for exposure, and provide a basis for further standardizing PEP.Methods:Based on surveillance data from the rabies exposure treatment clinic vaccination information system, population, and spatial administrative division data in Shandong province from 2019 to 2023, descriptive epidemiological methods were applied to analyze using SPSS 18.0.Results:The number of individuals receiving post-exposure treatment at PEP clinics in Shandong province from 2019 to 2023 was over 1 million annually and showed an increasing trend year by year, with the highest number of visits occurring from May to August each year. The number of female patients is increasing year by year. The 15-year-old and younger age group accounted for 31.69%-36.86% of clinic visits. Grade Ⅲ exposures accounted for 53.40%, and limbs accounted for approximately 89.81% of exposed areas. Approximately 1.94% is multi site exposure. The main injuring animals were dogs, followed by cats, and the proportion of cats is increasing year by year. The proportion of doctor′s office visitors who self-treated wounds increased from 32.32% to 45.46%, while the proportion of outpatient wound treatment decreased from 76.07% to 66.24%. The whole course vaccination rate after initial exposure is 63.79%. The whole course vaccination rate for the 15-29-year-old age group was lower than that for other age groups. The usage rate of passive immune preparations among grade Ⅲ exposed individuals is 35.66%. From 2019 to 2023, 8 cases of rabies were reported, none of whom received standard post-exposure treatment.Conclusions:The epidemic characteristics and exposure risk of people exposed to suspected rabies animals in Shandong province have changed. It is necessary to pay attention to the female population, the population with low vaccination rate between 15 to 29 years of age, cat bitten people, and carry out continuous monitoring on the exposed population, and timely adjust the prevention and control strategies.

Objective    To investigate the effect of simvastatin and mechanical pretreatment on intimal hyperplasia of venous graft and its mechanism. Methods    Twelve New Zealand rabbits were selected and randomly divided into 4 groups: a blank control group, a simvastatin topical treatment group, a mechanical precondition group and a combined group (n=3 in each group). Ultrasound was used to evaluate the changes of graft wall and blood flow velocity in the graft, and pathological section was used to evaluate the intimal hyperplasia. Human umbilical cord endodermal cells were cultured in vitro. A simvastatin group and a solvent control group were set to detect YAP phosphorylation, downstream target gene expression and cell proliferation. Results    Vascular ultrasound showed that except the simvastatin topical treatment group, the flow velocity in vein grafts in the other three groups significantly increased 21 days after surgery compared with 7 days after surgery (P<0.01). Pathological sections showed that the thickness of new intima in the simvastatin topical treatment group, mechanical precondition group, combined group and blank control group were 45.56±4.11 μm, 201.28±16.71 μm, 143.57±7.82 μm, 249.45±13.33 μm, respectively, and there were statistical differences compared with the blank control group (P<0.05). In vitro results showed that compared with the solvent control group, cell death was observed in high concentration simvastatin (5 mmol/L) group, cell proliferation was inhibited in low concentration simvastatin (2.5 mmol/L) group (P<0.05), the expression of YAP protein in the simvastatin group was unchanged, but the expression of phosphorylated YAP protein significantly increased (P<0.05), and the expression of downstream target gene ccn1 was down-regulated (P<0.001). Conclusion    Intravascular local application of simvastatin and mechanical preconditioning alone or in combination can inhibit intimal hyperplasia of venous graft. High concentration of simvastatin has cytotoxicity, while low concentration of simvastatin has inhibitory effect on cell proliferation. Simvastatin can inhibit the formation of new intima by inhibiting the entry of YAP into the nucleus and reducing the transcription of cell proliferation-related target gene ccn1.

Objective:To explore the structure and function of recombination activating gene 1 (RAG1) related to severe combined immunodeficiency (SCID) before entering the preimplantation genetic testing for monogenic (PGT-M) cycle, and to predict the pathogenicity of its novel mutation sites.Methods:According to the whole exome sequencing reports of the probands in the Department of Reproductive Medicine, the First Affiliated Hospital of Sun Yat-sen University on August 2016, the chromosome karyotypes and Sanger sequencing of their parents from their peripheral blood, the structures and protein conserved domains of the novel mutation sites of RAG1 gene were analyzed by PROVEAN, PolyPhen-2 and Mutation Taster software, and the secondary and tertiary structures of the mutant and wild type RAG1 protein were reconstructed in three-dimensional structure to predict its pathogenicity. Results:The couple were carriers of RAG1 gene mutation, which were located on chromosome 11. The female was heterozygous missense mutation of c.946T>G (p.C316G) and the male was heterozygous integer mutation of c.1194_1196del (p.L399del). The amino acid of the RAG1 mutations mentioned above were highly conserved among human, chimpanzee, pig, cattle, rats and mice. The secondary and tertiary structure reconstruction showed that the RING-type zinc finger structure lost the ability to bind zinc ions due to c.946T>G mutation, and the deletion of leucine at position 399 caused by c.1194_1196del mutation reduced one hydrogen bond. Conclusion:It is speculated that the two novel mutation sites of RAG1 are pathogenic mutations, which expand the mutation spectrum of RAG1 gene and have important research value.