To investigate the mechanism of Jianpi Qutan Formula in regulating the balance between classically activated macrophages(M1) and alternatively activated macrophages(M2) in atherosclerotic plaques through phosphorylation and activation of the signal transducer and activator of transcription 6(STAT6), thereby reducing inflammation, increasing plaque stability, and exerting anti-atherosclerosis(AS) effects. An AS model was established by feeding apolipoprotein E(ApoE)~(-/-) mice with atherosclerotic chow for 8 weeks. The ApoE~(-/-) mice were randomly divided into a model group(Mod group), a Jianpi Qutan Formula group(JPQT group, 8.97 g·kg~(-1)), and a Atorvastatin Calcium Tablets group(ATO group, 1.3 mg·kg~(-1)) according to a random table method, with 10 mice in each group. Additionally, 10 male C57BL/6J mice of the same age, fed with a normal diet, were set as the control group(Con group). The JPQT and ATO groups received their respective treatments via oral gavage for 8 consecutive weeks, while the Con and Mod groups were administered an equivalent volume of saline. Body weight was continuously monitored, and after blood collection, total cholesterol(TC) and triglyceride(TG) levels in the serum of each group were compared. Hematoxylin-eosin(HE) staining and oil red O staining were used to observe plaque formation in aortic tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the expression levels of pro-inflammatory cytokines interleukin(IL)-6 and IL-12, as well as the anti-inflammatory cytokine IL-10. Immunofluorescence was used to detect the positive expression of aortic cluster of differentiation(CD)86 and CD206. Western blot analysis was conducted to detect the protein expression levels of aortic inducible nitric oxide synthase(iNOS), arginase 1(Arg1), STAT6, and p-STAT6. Compared to the Con group, the Mod group exhibited increased body weight and blood lipid levels, disordered aortic structure, significant AS plaque formation accompanied by extensive lipid deposition, and elevated serum levels of pro-inflammatory cytokines IL-6 and IL-12, as well as elevated CD86 and iNOS protein levels. In contrast, the serum levels of the anti-inflammatory cytokine IL-10, along with the protein expression levels of CD206, Arg1, and p-STAT6/STAT6, were reduced. Compared to the Mod group, the drug intervention groups showed improvements in body weight and lipid metabolism, with a more significant improvement in aortic structure, reduced lipid accumulation, decreased serum levels of IL-6 and IL-12, and lower CD86 and iNOS protein levels. Meanwhile, levels of IL-10, CD206, Arg1, and p-STAT6/STAT6 increased. Jianpi Qutan Formula improves AS by regulating the imbalance in M1/M2 macrophage polarization, and its mechanism is likely closely related to the activation of the STAT6 signaling pathway.
Animals ; Atherosclerosis/metabolism* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Macrophages/cytology* ; Mice, Inbred C57BL ; STAT6 Transcription Factor/immunology* ; Humans ; Apolipoproteins E/genetics* ; Interleukin-6/immunology*

OBJECTIVE: To investigate the regulatory effects of two traditional mineral medicines (TMMs), Gypsum Fibrosum (Shigao, GF) and Terra Flava Usta (Zaoxintu, TFU), on gut-beneficial bacteria in mice, and preliminarily explore their mechanisms of action. METHODS: Mice were randomly divided into 3 groups (n=10 per group): the control group (standard diet), the GF group (diet supplemented with 2% GF), and the TFU group (diet supplemented with 2% TFU). After 4-week intervention, 16S rRNA gene sequencing was used to analyze the changes in the gut microbiota (GM). Scanning electron microscopy, in combination with coumarin A tetramethyl rhodamine conjugate and Hoechst stainings, was used to observe the bacteria and biofilm formation. RESULTS: Principal coordinate analysis revealed that GF and TFU significantly altered the GM composition in mice. Further analysis revealed that GF and TFU affected different types of gut bacteria, suggesting that different TMMs may selectively modulate specific bacterial populations. For certain bacteria, such as Faecalibaculum and Ileibacterium, both GF and TFU exhibited growth-promoting effects, implying that they may be sensitive to TMMs and that different TMMs can increase their abundance through their respective mechanisms. Notably, Lactobacillus reuteri, a widely recognized and used probiotic, was significantly enriched in the GF group. Random forest analysis identified Ileibacterium valens as a potential indicator bacterium for TMMs' impact on GM. Further mechanistic studies showed that gut bacteria formed biofilm structures on the TFU surface. CONCLUSIONS This study provides new insights into the interaction between TMMs and GM. As safe and effective natural clays, GF and TFU hold promise as potential candidates for prebiotic development.
Animals ; Gastrointestinal Microbiome/drug effects* ; Bacteria/growth & development* ; Mice ; Biofilms/drug effects* ; Male ; RNA, Ribosomal, 16S/genetics*

Additive manufacturing(3D printing)technology aligns with the direction of precision and customization in future medicine,presenting a significant opportunity for innovative development in high-end medical devices.Currently,research and industrialization of 3D printed medical devices mainly focus on nondegradable implants and degradable implants.Primary areas including metallic orthopaedic implants,polyether-ether-ketone(PEEK)bone implants,and biodegradable implants have been developed for clinical and industrial application.Recent research achievements in these areas are reviewed,with a discussion on the additive manufacturing technologies and applications for customized implants.Challenges faced by different types of implants are analyzed from technological,application,and regulatory perspectives.Furthermore,prospects and suggestions for future development are outlined.

Objective To investigate the age-related changes of the mandibular third molar root pulp visibility in individuals in East China,and to explore the feasibility of applying this method to deter-mine whether an individual is 18 years or older.Methods A total of 1 280 oral panoramic images were collected from the 15-30 years old East China population,and the mandibular third molar root pulp visibility in all oral panoramic images was evaluated using OLZE 0-3 four-stage method,and the age distribution of the samples at each stage was analyzed using descriptive statistics.Results Stages 0,1,2 and 3 first appeared in 16.88,19.18,21.91 and 25.44 years for males and in 17.47,20.91,22.01 and 26.01 years for females.In all samples,individuals at stages 1 to 3 were over 18 years old.Conclusion It is feasible to determine whether an individual in East China is 18 years or older based on the mandibular third molar root pulp visibility on oral panoramic images.

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Sphingosine 1-phosphate receptor 1(S1PR1)is currently a popular research target for the treatment of immune-related diseases,but it also has potential cardiac safety risks.This article summarizes the experience of the completed phase Ⅰ clinical trial of S1PR1 innovative drug and discusses the necessity and implementation points of cardiac safety risk management and control in the phase Ⅰ clinical trial of S1PR1 innovative drug by summarizing the experience of the completed phase Ⅰclinical trial of S1PR1 innovative drug,combined with the guiding principles of risk identification and control strategy for early clinical trial and clinical evaluation of drug QT at home and abroad,for the reference of the industry.

Objective:To observe the therapeutic effect of Shengsan Jiedu Huayu decoction in alleviating inflammatory liver injury in rats with acute-on-chronic liver failure (ACLF) and its effect on the activation intensity for the NLRP3 signaling pathway.Methods:63 SD rats were randomly divided into a blank group, a model group, and low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction (7.29 g/kg/d, 14.58 g/kg/d, and 29.16 g/kg/d). The ACLF rat model was replicated using carbon tetrachloride combined with d-galactosamine and lipopolysaccharide. Different dose gradients of the Shengsan Jiedu Huayu decoction were used for a five-day intervention treatment, and then rat serum and tissue samples were collected. A biochemical analyzer was used to detect the serum levels of ALT, AST, and TBIL in rats. ELISA was used to detect serum IL-18 and IL-1β content. HE staining was used to observe histomorphological changes in liver tissue. Immunohistochemistry was used to detect GSDMD expression in liver tissue. Western blot and PCR were used to detect NLRP3, Caspase1, ASC, TLR4, IL-1β, IL-18 protein, and mRNA expression levels.The groups were compared using analysis of variance and the rank-sum test.Results:Compared with the blank group, the model group’s rat liver tissue was severely injured. Serum levels of ALT, AST, and TBIL, inflammatory factors IL-1β and IL-18, and the GSDMD protein expression level, NLRP3 expression level, TLR4, caspase 1, ASC, IL-1β, IL-18 protein, and mRNA ( P<0.01) were all significantly increased in the model than the blank group ( P<0.01). Additionally, compared with the model group, the low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction had improved liver tissue injury in ACLF rats, while the serum levels of ALT, AST, TBIL, IL-1β, IL-18, liver tissue GSDMD protein, NLRP3, TLR4, caspase 1, and ASC expressions were all lower in the different dose gradients of the Shengsan Jiedu Huayu decoction than the model group, with the most evident reduction in the high-dose group ( P<0.01). Conclusion:Shengsan Jiedu Huayu decoction can weaken the activation intensity of the NLRP3 signaling pathway, alleviate liver tissue pathological injury, reduce inflammatory factor release, and alleviate inflammatory liver injury in ACLF rats.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective To design and validate a novel surgical guide for retrieval of foreign body in jaw. Methods Firstly, a surgical guide based on cone beam computed tomography and trephine technique was designed to remove broken dental instrument fragments. Its feasibility and accuracy were assessed by removing broken dental instrument in goat mandible, and then it was successfully applied in clinical cases. The linear and angular discrepancies between actual and planned columnar bone with imaginary fragment was analyzed. The euclidean distance was measured at the hex and apex of the columnar bone and the angle of axis deviation was also calculated. We obtained seven parameters (cdh, cda, hdh, hda, vdh, vda, and ad) to describe deviations. Results Mean central deviation at the hex and apex was (0.51 ± 0.14) mm and (0.62 ± 0.19) mm, respectively. Accompanying mean values were as follow: horizontal deviation at the hex was (0.48 ± 0.16) mm, horizontal deviation at the apex was (0.52 ± 0.22) mm, vertical deviation at the hex was (0.17 ± 0.09) mm, vertical deviation at the apex was (0.29 ± 0.13) mm, and angular deviation of (5.38 ± 3.43) degrees. In a clinical case, the guide successfully located and removed the fracture file. Conclusion This study reveals that this kind novel surgical guide could aid to locate and remove the foreign body in jaw.