ObjectiveTo explore the differences in the accumulation of secondary metabolites of Dendrobium nobile cultivated on epiphytic stones and trees， so as to elucidate the scientific connotation of "only those that grow on stones has superior quality"， and provide a direction for the cultivation and quality evaluation of D. nobile. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS）-based widely targeted metabolomics was used to detect the metabolites of D. nobile cultivated on epiphytic stones and trees. And the combination of principal component analysis（PCA）， hierarchical cluster analysis（HCA）， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was performed for multivariate statistical analysis of metabolites. Differential metabolites were screened by variable importance in the projection（VIP） value≥1 and log₂fold change（FC）≥1 or ≤-1， and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis was conducted. ResultsA total of 1 267 metabolites were identified in the stems of D. nobile from the two cultivation modes， dominated by flavonoids（292）， phenolic acids（284）， and alkaloids（189）. Through OPLS-DA screening， 473 differential metabolites were obtained. Compared to epiphytic tree-cultivated D. nobile， epiphytic stone-cultivated D. nobile exhibited upregulation of flavonoids， phenolic acids， alkaloids， lignans and coumarins， while quinones and terpenoids were down-regulated. The differential metabolites mainly included flavonoid glycosides and alkaloids， and these differential metabolites significantly contributed to characterizing the two cultivation patterns. KEGG enrichment analysis revealed significant enrichment in pathways of flavone and flavonol biosynthesis， flavonoid biosynthesis， tyrosine metabolism， and phenylalanine metabolism in epiphytic stone-cultivated D. nobile. ConclusionEpiphytic stone cultivation is beneficial for the accumulation of phenolic acids， flavonoids， and alkaloids in D. nobile， indicating that the "only those that grow on stones has superior quality" documented in the materia medica has certain scientific basis， and the findings also provide a reference for quality evaluation and discrimination research between epiphytic stone and tree cultivated D. nobile.

Objective:To understand the trends of the disease burden of Alzheimer's disease(AD)attributable to high body mass index(BMI)and high fasting plasma glucose(FPG)in the past 30 years and future trends in China, and to provide suggestions for the prevention and treatment of AD.Methods:Based on the Global Burden of Disease Research Database(GBD), data on AD deaths and disability adjusted life years(DALYs)attributable to high BMI and high FPG were collected from 1990 to 2021 in Chinese and global populations.The Joinpoint log-linear regression model was used to explore and compare the changing trends of AD burden in China and globally from 1990 to 2021, and a Bayesian age-period-cohort model was constructed for predictive analysis.Results:In 2021, the age-standardized mortality and DALYs rates of AD attributed to high BMI in the Chinese population were 1.256/100, 000 and 24.751/100, 000, respectively, and those attributed to high FPG were 3.636/100, 000 and 66.721/100, 000, respectively.The age-standardized rates of mortality and DALYs of females were both higher than those of males.From 1990 to 2021, the age-standardized rates of mortality and DALYs of AD attributed to high BMI increased slowly at first and then rapidly in China, the corresponding average annual percent change(AAPC)and 95% confidence interval(95% CI)were 9.87%(9.63%-10.12%), and 9.81%(9.54%-10.09%), respectively( P<0.001). The age-standardized rates of mortality and DALYs of AD caused by high FPG showed a fluctuating upward trend, with AAPC of 0.29%(95% CI: 0.17%-0.41%)and 0.53%(95% CI: 0.45%-0.61%), respectively( P<0.001). It is predicted that by 2030, the age-standardized rates of mortality and DALYs of AD attributed to high BMI and high FPG in the whole population of China will increase to 4.87/100 000 and 97.20/100 000, both lower than the global level(5.45/100 000 and 100.24/100 000). In addition to a slight decline in the age-standardized mortality rate in Chinese men, the age-standardized rates of mortality and DALYs attributed to high BMI and high FPG in Chinese women and the global population will both show an upward trend. Conclusions:The burden of AD attributed to high BMI and high FPG is relatively severe, with gender differences, and is expected to increase slightly by 2030.It is recommended that early identification of key high-risk populations of AD should be strengthened, especially for the elderly and female groups.Interventions targeting modifiable risk factors should be carried out, and effective measures should be adopted to reduce the burden of AD.

Objective:To understand the trends of the disease burden of Alzheimer's disease(AD)attributable to high body mass index(BMI)and high fasting plasma glucose(FPG)in the past 30 years and future trends in China, and to provide suggestions for the prevention and treatment of AD.Methods:Based on the Global Burden of Disease Research Database(GBD), data on AD deaths and disability adjusted life years(DALYs)attributable to high BMI and high FPG were collected from 1990 to 2021 in Chinese and global populations.The Joinpoint log-linear regression model was used to explore and compare the changing trends of AD burden in China and globally from 1990 to 2021, and a Bayesian age-period-cohort model was constructed for predictive analysis.Results:In 2021, the age-standardized mortality and DALYs rates of AD attributed to high BMI in the Chinese population were 1.256/100, 000 and 24.751/100, 000, respectively, and those attributed to high FPG were 3.636/100, 000 and 66.721/100, 000, respectively.The age-standardized rates of mortality and DALYs of females were both higher than those of males.From 1990 to 2021, the age-standardized rates of mortality and DALYs of AD attributed to high BMI increased slowly at first and then rapidly in China, the corresponding average annual percent change(AAPC)and 95% confidence interval(95% CI)were 9.87%(9.63%-10.12%), and 9.81%(9.54%-10.09%), respectively( P<0.001). The age-standardized rates of mortality and DALYs of AD caused by high FPG showed a fluctuating upward trend, with AAPC of 0.29%(95% CI: 0.17%-0.41%)and 0.53%(95% CI: 0.45%-0.61%), respectively( P<0.001). It is predicted that by 2030, the age-standardized rates of mortality and DALYs of AD attributed to high BMI and high FPG in the whole population of China will increase to 4.87/100 000 and 97.20/100 000, both lower than the global level(5.45/100 000 and 100.24/100 000). In addition to a slight decline in the age-standardized mortality rate in Chinese men, the age-standardized rates of mortality and DALYs attributed to high BMI and high FPG in Chinese women and the global population will both show an upward trend. Conclusions:The burden of AD attributed to high BMI and high FPG is relatively severe, with gender differences, and is expected to increase slightly by 2030.It is recommended that early identification of key high-risk populations of AD should be strengthened, especially for the elderly and female groups.Interventions targeting modifiable risk factors should be carried out, and effective measures should be adopted to reduce the burden of AD.

Objective To analyze and compare the change of disease burden attributed to high temperature in the Chinese population in 2019 compared with 1990. Methods Based on the global burden of disease study data in 2019, the number of deaths, mortality, disability-adjusted life years (DALY) and DALY rate attributable to high temperature in Chinese population of different ages and genders in 1990 and 2019 were extracted to analyze the changing trend of disease burden attributable to high temperature exposure in Chinese population and its main causes. The Joinpoint regression model was used to analyze the trend of changes in standardized attributable DALY rates. Results Compared with 1990, the number of disease deaths attributable to high temperature in China in 2019 increased from 10 700 to 13 900, and the attributable DALY decreased from 532,200 to 276 100 person-years. The standardized mortality and DALY rates decreased by 35.25% and 65.20%, respectively. The burden attributable to high temperature was higher in males than in females, and the burden was relatively heavier in the population aged 70 and above. In 2019, chronic non-communicable diseases were the main cause of the attributable burden of high temperature exposure, and ischemic heart disease had the highest DALY burden, with an age-standardized DALY rate of 4.64/100 000. Conclusion The absolute death burden attributable to high temperature exposure in Chinese population is still increasing. It is necessary to pay more attention to high-risk groups such as men and the elderly, continue to strengthen environmental protection, and formulate relevant interventions in a targeted way to further reduce the disease burden caused by high temperature exposure.

Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.

Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

Objective:To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD).Methods:A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results:A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion:The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.