BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P＜0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P＜0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P＜0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.

BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P＜0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P＜0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P＜0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.

Objective: To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials. Methods: The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group Results: The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group. Conclusion The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.

To guide transfusion practice in critically ill children who often need plasma and platelet transfusions, the Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB) developed Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children. This guideline addresses 53 recommendations related to plasma and platelet transfusion in critically ill children with 8 kinds of diseases, laboratory testing, selection/treatment of plasma and platelet components, and research priorities. This paper introduces the specific methods and results of the recommendation formation of the guideline.

Objective The results of ASTRUM-007 reveal the clinical benefits of PD-L1-positive esophageal squamous cell carcinoma(ESCC)patients.This study aims to analyze the economics of first-line treatment of PD-L1-positive ESCC with brucella combined with chemotherapy from the perspective of China's health system.Methods A three-state partitioned survival model(PSM)including progression-free survival(PFS),disease progression(PD),and death(D)was established to evaluate the economy of serplulimab combined with chemotherapy,the first-line treatment for PD-L1 positive advanced ESCC,compared with the placebo combination chemotherapy.The cycle period was two weeks,the horizon of the simulation was a lifetime,and the annual discount rate was set to 5%.The main outcome parameters are total cost,quality-adjusted life year(QALY),and incremental cost-effectiveness ratio(ICER).One-way sensitivity analysis(OWSA),probability sensitivity analysis(PSA),and scenario analysis were used to evaluate the impact of the change of important parameters in the model on ICER.Results The basic results showed that the incremental effect and incremental cost of the serplulimab combined with chemotherapy compared with the placebo combination chemotherapy were 1.281 QALYs and 266 573.26 yuan,respectively,and the ICER was 208 166.24 yuan/QALY.OWSA showed that the price of serplulimab was the most sensitive parameter to ICER;PSA showed that when the WTP threshold was three times China's per capita GDP in 2022,Serplulimab combined with chemotherapy was significantly more economical than the placebo combination chemotherapy;scenario analysis revealed that according to the ASTRUM-007 study in the Central Asian group and the charitable drug donation program of serplulimab:in patients with PD-L1 1≤CPS<10,ICER was 205 056.83 yuan/QALY;with 218 022.59/QALY in patients with PD-L1 CPS≥10,and the mean value of ICER was lower than three times of China's per capita GDP.The ICER of all patients was 59 046.65 yuan/QALY,with 68 294.42 yuan/QALY of patients with PD-L1 1≤CPS<10,44 744.02 yuan/QALY of patients with PD-L1 CPS≥10.The ICER value was lower than China's per capita GDP.Conclusion Serplulimab combined with chemotherapy is more economical than placebo combined with chemotherapy in the treatment of PD-L1-positive ESCC patients.

Objective To analyze the seroepidemiology characteristics of Epstein-Barr virus(EBV)infection in children in Shenyang.Methods From June 2022 to May 2023,serum was collected from 12 083 children at Shengjing hospital of China Medical University.Serum capsid antigen(VCA)-IgM,VCA-IgG,EBV nuclear antigen-IgG(EBNA-IgG),and early antigen-IgG(EA-IgG)antibodies were detected using the LIAISION chemiluminescence immunoassay.EBV-DNA was detected using real-time PCR.Differences in antibody positivity rates between sexes,ages,and seasons of onset were compared.Results In 12 083 patients,the positive rates of VCA-IgM,VCA-IgG,EBNA-IgG,and EA-IgG were 9.95％(1 202/12 083),50.57％(6 110/12 083),46.03％(5 562/12 083)and 4.93％(596/12 083).The positive rates of VCA-IgM and EA-IgG were lower in male patients(9.09％and 4.44％,respectively)than in female patients(11.10％,5.60％;all P＜0.05).The differences in the positive rates for VCA-IgM,VCA-IgG,EBNA-IgG,and EA-IgG antibodies in children of different ages were statistically significant(all P＜0.05).Differences in the positive rates of VCA-IgG,EBNA-IgG,and EA-IgG antibodies were statistically significant when compared between seasons(all P＜0.05).Fourteen EBV antibody-positive combinations were detected,of which the main combination was VCA-IgG and EBNA-IgG double-positive,with a total of 4 741 cases(39.24％).Of the 3 712 children who underwent EBV-DNA detection testing,3 034(81.73％)were EBV-DNA-negative and 678(18.27％)were EBV-DNA-posi-tive.VCA-IgG and EBNA-IgG double positivity was the most common in EBV-DNA-negative and EBV-DNA-positive children,accounting for 983(26.48％)and 194 cases(5.23％),respectively.Conclusion Both VCA-IgG and EBNA-IgG antibodies are main positive in children with EBV infection in Shenyang.The positive rate of EBV antibodies is lower in boys than in girls.The positive rates of EBV anti-bodies differ in children of different ages and seasons of onset.

Objective:To evaluate the clinical application and biomechanical characteristics of zygomatic implant supported prosthesis (ZIP) in restoring unilateral maxillary defect and to provide theoretical support for clinical treatment.Methods:A total of 8 patients with unilateral maxillary defect admitted to the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to June 2018 were selected. Inclusion criteria: unilateral maxillary defect, 18 to 70 years old, no systemic chronic disease, no radiotherapy history, healthy residual dentition, no moderate to severe periodontitis, no loose teeth, and no obvious malocclusion. Two zygomatic implants were implanted on the affected side, and the defects were restored with removable prostheses (RP) immediately after the operation. ZIP was manufactured and placed 6-12 months after implantation. And then, the quality of life after wearing RP and ZIP was evaluated with Dental Impact on Daily Living scale (DIDL). The subjective feelings of patients were evaluated from five aspects of appearance, pain, oral comfort, eating and chewing and general performance. The results were statistically analyzed by independent sample t test. A three dimension model of skull was established with the CT data of a 25-year-old healthy male and the models of zygomatic implants and prosthesis were constructed at the same time. In this composite model, a 150 N vertical force was loaded on the occlusal surface of the prosthetic prosthesis to simulate the bite force, and the stress distribution and concentration points of the zygomatic implant, prosthetic clasps, palatal plate, abutment and other parts were analyzed. The differences between RP and ZIP restoration were compared. Results:A total of 8 patients with unilateral maxillary defect were selected, including 5 males and 3 females, aged from 18 to 63 years, with an average of 48.9 years. A total of 16 zygomatic implants were implanted in 8 patients, and ZIP repair was completed 9-10 months after operation. The result of DIDL scale showed that, in terms of appearance, oral comfort, eating and chewing, general performance, the score of ZIP group was 0.79±0.15, 0.70±0.15, 0.63±0.24, 0.73±0.13 respectively, all of which were significantly higher than those of RP group -0.41±0.22, 0.35±0.22, -0.09±0.34, 0.30±0.19 respectively. Nevertheless, the score of ZIP group in terms of pain was 0.29±0.15, which was lower than that of RP group (0.48±0.23). Except for pain, the other differences were statistically significant ( P<0.05). The biomechanical analysis showed that, compared with RP group, the stress of ZIP was distributed mainly in the zygomatic implants. And the stress of palatal plates, clasps and abutments was reduced significantly and distributed evenly, with no obviously stress concentration point. Conclusions:ZIP can improve appearance, reduce discomfort and increase mastication efficiency. It is a better choice for unilateral maxillary defect restoration.

Objective:To evaluate the clinical application and biomechanical characteristics of zygomatic implant supported prosthesis (ZIP) in restoring unilateral maxillary defect and to provide theoretical support for clinical treatment.Methods:A total of 8 patients with unilateral maxillary defect admitted to the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to June 2018 were selected. Inclusion criteria: unilateral maxillary defect, 18 to 70 years old, no systemic chronic disease, no radiotherapy history, healthy residual dentition, no moderate to severe periodontitis, no loose teeth, and no obvious malocclusion. Two zygomatic implants were implanted on the affected side, and the defects were restored with removable prostheses (RP) immediately after the operation. ZIP was manufactured and placed 6-12 months after implantation. And then, the quality of life after wearing RP and ZIP was evaluated with Dental Impact on Daily Living scale (DIDL). The subjective feelings of patients were evaluated from five aspects of appearance, pain, oral comfort, eating and chewing and general performance. The results were statistically analyzed by independent sample t test. A three dimension model of skull was established with the CT data of a 25-year-old healthy male and the models of zygomatic implants and prosthesis were constructed at the same time. In this composite model, a 150 N vertical force was loaded on the occlusal surface of the prosthetic prosthesis to simulate the bite force, and the stress distribution and concentration points of the zygomatic implant, prosthetic clasps, palatal plate, abutment and other parts were analyzed. The differences between RP and ZIP restoration were compared. Results:A total of 8 patients with unilateral maxillary defect were selected, including 5 males and 3 females, aged from 18 to 63 years, with an average of 48.9 years. A total of 16 zygomatic implants were implanted in 8 patients, and ZIP repair was completed 9-10 months after operation. The result of DIDL scale showed that, in terms of appearance, oral comfort, eating and chewing, general performance, the score of ZIP group was 0.79±0.15, 0.70±0.15, 0.63±0.24, 0.73±0.13 respectively, all of which were significantly higher than those of RP group -0.41±0.22, 0.35±0.22, -0.09±0.34, 0.30±0.19 respectively. Nevertheless, the score of ZIP group in terms of pain was 0.29±0.15, which was lower than that of RP group (0.48±0.23). Except for pain, the other differences were statistically significant ( P<0.05). The biomechanical analysis showed that, compared with RP group, the stress of ZIP was distributed mainly in the zygomatic implants. And the stress of palatal plates, clasps and abutments was reduced significantly and distributed evenly, with no obviously stress concentration point. Conclusions:ZIP can improve appearance, reduce discomfort and increase mastication efficiency. It is a better choice for unilateral maxillary defect restoration.

Objective: To investigate the automatic implicit attitude and explicit stigma of mental illness, and the intervention effectiveness on the stigma of mental illness in college students. Methods: Single category implicit association test(SC-IAT) and questionnaire survey were used to study the degree of implicit and explicit mental illness stigma among 30 college students of Peking University, and investigated the effect of two strategies, education and contact.Data were analyzed by SPSS 22.0 with t-test and variance analysis. Results: The D values of SC-IAT in the three dimensions of cognitive evaluation, emotional response and behavioral tendency of college students were 0.29±0.37, 0.24±0.43, and 0.10±0.43.There was a statistically significant difference between the cognitive evaluation dimension, the emotional response dimension and 0(t=4.069, P<0.01; t=2.925, P<0.01). There was no statistically significant difference between the implicit stigma and the 0 in the behavioral tendency dimension(t=1.423, P=0.167). In the explicit stigma, the mercy dimension score(1.94±0.61) was lower than the median, and the difference was statistically significant(t=-12.286, P<0.01), while the scores of anger dimension(4.62±0.44) and fear dimension (4.55±0.31) were higher than the median(t=13.243, 3.200, both P<0.01). There were no significant differences in the values of implicit and external stigma among pre-intervention, education intervention and after contact(P>0.05). The correct rates of questions "Which of the following situations do you think are considered mentally unhealthy? " and "Which of the following disorders are mental illnesses" (42±13)%, (54±13)%) increased after receiving educational intervention ((49±12)%, (64±13)%), the difference was statistically significant (F=3.682, P<0.05; F=3.576, P<0.05). Conclusion College students have implicit mental illness stigma, educational and contact intervention strategies can help improve college students' understanding of relevant knowledge, and cannot improve the level of implicit stigma of college students on mental illness.

Objective: To discuss possible ethical and boundary issues when contacting clients through WeChat in different situations. Methods: Self-made questionnaires were utilized to investigate 194 counselors' (18 counselors gave clients their job WeChat ID, 64 counselors gave their private WeChat ID, and 115 counselors do not give WeChat toclients) attitudes and behaviors of encountering multiple relationship issues when using WeChat Results: For WeChat boundary, counselors who had job WeChat ID would post more private photos and videos on the post than counselors with no job ID and without ID(P <0.01). Although 41％ of counselors would use WeChat during the counseling and other related activities, only 10％ of the counselors had job ID. Counselors with no ID tended to accept clients breaking the boundaries through other ways (P <0.01). Conclusion: The study indicates that counselors have encountered ethic issues of multiple relationships when using WeChat Counselors who only have private WeChat ID should increase their sensitivity of the boundary issues in the use of WeChat.