ObjectiveWe reviewed the existing experimental studies about renal injury-inducing Chinese medicine and systematically analyzed the toxicity mechanisms， toxic components， toxicity attenuation measures， and modern evaluation methods of renal injury-inducing Chinese medicine. The results are expected to provide new ideas for the modern research on kidney injury-inducing Chinese medicine， offer new breakthrough points for the toxicity attenuation of Chinese medicine by compatibility and processing， and give insights into the future research of Chinese medicine toxicology on the basis of ensuring the safety and scientific application of Chinese medicine. MethodsThe animal， cell， and clinical studies of kidney injury-inducing Chinese medicine were retrieved from CNKI， Wanfang Data， VIP， PubMed， and Web of Science. The names and toxic components of renal injury-inducing Chinese medicine， renal injury sites， toxicity mechanisms， toxicity attenuation measures， and related evaluation methods were summarized. ResultsThe toxicity mechanisms of kidney injury-inducing Chinese medicine mainly involved oxidative stress， endoplasmic reticulum stress， inflammatory cell infiltration， and organic anion transporters. Processing and compatibility were the main toxicity attenuation measures. The evaluation methods encompassed animal experiments， cell models， network pharmacology， metabolomics， toxicology genomics， and fluorescent probe technology. ConclusionAt present， the toxicological verification of kidney injury-inducing Chinese medicine starts from toxic components and combines various experimental methods， which is more comprehensive and systematic than the previous studies based on only animal experiments. According to the classical theories of traditional Chinese medicine， the toxicity of kidney injury-inducing Chinese medicine is mainly attenuated by decocting in water， steaming， and frying. With the progress of science and technology， new processing methods for toxicity attenuation are emerging， and structural transformation， fermentation， and microwave methods are the key research directions of toxicity attenuation of Chinese medicine in recent years.

ObjectiveWe reviewed the existing experimental studies about renal injury-inducing Chinese medicine and systematically analyzed the toxicity mechanisms， toxic components， toxicity attenuation measures， and modern evaluation methods of renal injury-inducing Chinese medicine. The results are expected to provide new ideas for the modern research on kidney injury-inducing Chinese medicine， offer new breakthrough points for the toxicity attenuation of Chinese medicine by compatibility and processing， and give insights into the future research of Chinese medicine toxicology on the basis of ensuring the safety and scientific application of Chinese medicine. MethodsThe animal， cell， and clinical studies of kidney injury-inducing Chinese medicine were retrieved from CNKI， Wanfang Data， VIP， PubMed， and Web of Science. The names and toxic components of renal injury-inducing Chinese medicine， renal injury sites， toxicity mechanisms， toxicity attenuation measures， and related evaluation methods were summarized. ResultsThe toxicity mechanisms of kidney injury-inducing Chinese medicine mainly involved oxidative stress， endoplasmic reticulum stress， inflammatory cell infiltration， and organic anion transporters. Processing and compatibility were the main toxicity attenuation measures. The evaluation methods encompassed animal experiments， cell models， network pharmacology， metabolomics， toxicology genomics， and fluorescent probe technology. ConclusionAt present， the toxicological verification of kidney injury-inducing Chinese medicine starts from toxic components and combines various experimental methods， which is more comprehensive and systematic than the previous studies based on only animal experiments. According to the classical theories of traditional Chinese medicine， the toxicity of kidney injury-inducing Chinese medicine is mainly attenuated by decocting in water， steaming， and frying. With the progress of science and technology， new processing methods for toxicity attenuation are emerging， and structural transformation， fermentation， and microwave methods are the key research directions of toxicity attenuation of Chinese medicine in recent years.

Objectives: This study evaluates the efficacy of a new temporomandibular joint (TMJ) capsule suspension technique for stabilizing the TMJ after free fibular flap reconstruction of the mandibular condyle. Patients and Methods: Patients undergoing the TMJ capsule suspension technique during free fibular flap reconstruction after mandibulectomy with condylectomy (study group; n=9) were compared with a control group (n=9). Mandibular movement trajectory and surface electromyographic signals of bilateral masseters were recorded. The neocondyle–disc relationship was examined with magnetic resonance imaging (MRI) at 6 months after surgery. Results: Maximal mouth opening and bilateral marginal movement distances were comparable between the two groups (P>0.05). The asymmetry index of the condyle path length was significantly higher in controls (P=0.02). Bilateral mouth opening trajectories were symmetric in 7 patients and deviated to the affected side in 2 patients in the study group; they deviated to the affected side in all controls. The mean electromyographic values of the masseter on the affected side in resting, maximum bite, and chewing states were comparable between the two groups (P=0.13, P=0.65, and P=0.82, respectively). On MRI at 6 months, the thicknesses of the anterior, medial, and posterior bands and TMJ disc length were similar on the affected and normal sides in the study group (P=0.57, P=0.13, P=0.48, and P=0.87, respectively). Conclusion The proposed TMJ capsule suspension technique could improve postoperative TMJ structure and function after fibular free flap reconstruction following mandibulectomy with condylectomy.

Objectives: This study evaluates the efficacy of a new temporomandibular joint (TMJ) capsule suspension technique for stabilizing the TMJ after free fibular flap reconstruction of the mandibular condyle. Patients and Methods: Patients undergoing the TMJ capsule suspension technique during free fibular flap reconstruction after mandibulectomy with condylectomy (study group; n=9) were compared with a control group (n=9). Mandibular movement trajectory and surface electromyographic signals of bilateral masseters were recorded. The neocondyle–disc relationship was examined with magnetic resonance imaging (MRI) at 6 months after surgery. Results: Maximal mouth opening and bilateral marginal movement distances were comparable between the two groups (P>0.05). The asymmetry index of the condyle path length was significantly higher in controls (P=0.02). Bilateral mouth opening trajectories were symmetric in 7 patients and deviated to the affected side in 2 patients in the study group; they deviated to the affected side in all controls. The mean electromyographic values of the masseter on the affected side in resting, maximum bite, and chewing states were comparable between the two groups (P=0.13, P=0.65, and P=0.82, respectively). On MRI at 6 months, the thicknesses of the anterior, medial, and posterior bands and TMJ disc length were similar on the affected and normal sides in the study group (P=0.57, P=0.13, P=0.48, and P=0.87, respectively). Conclusion The proposed TMJ capsule suspension technique could improve postoperative TMJ structure and function after fibular free flap reconstruction following mandibulectomy with condylectomy.

Objectives: This study evaluates the efficacy of a new temporomandibular joint (TMJ) capsule suspension technique for stabilizing the TMJ after free fibular flap reconstruction of the mandibular condyle. Patients and Methods: Patients undergoing the TMJ capsule suspension technique during free fibular flap reconstruction after mandibulectomy with condylectomy (study group; n=9) were compared with a control group (n=9). Mandibular movement trajectory and surface electromyographic signals of bilateral masseters were recorded. The neocondyle–disc relationship was examined with magnetic resonance imaging (MRI) at 6 months after surgery. Results: Maximal mouth opening and bilateral marginal movement distances were comparable between the two groups (P>0.05). The asymmetry index of the condyle path length was significantly higher in controls (P=0.02). Bilateral mouth opening trajectories were symmetric in 7 patients and deviated to the affected side in 2 patients in the study group; they deviated to the affected side in all controls. The mean electromyographic values of the masseter on the affected side in resting, maximum bite, and chewing states were comparable between the two groups (P=0.13, P=0.65, and P=0.82, respectively). On MRI at 6 months, the thicknesses of the anterior, medial, and posterior bands and TMJ disc length were similar on the affected and normal sides in the study group (P=0.57, P=0.13, P=0.48, and P=0.87, respectively). Conclusion The proposed TMJ capsule suspension technique could improve postoperative TMJ structure and function after fibular free flap reconstruction following mandibulectomy with condylectomy.

Objective:To investigate the conversion of stromal vascular fraction (SVF) in the microenvironment of radiation-induced skin injuries to provide guidance for clinical applications.Methods:Based on a random number table, C57BL/6N mice were categorized into four groups: the blank control, negative control, acute injury, and chronic injury groups, with each group containing 25 mice. The backs of mice in the blank control, acute injury, and chronic injury groups were exposed to 15 Gy X-ray irradiation. Then, the mice in the negative control, acute injury, and chronic injury groups were injected subcutaneously with the SVF derived from B6/G-R mice. The survival of these mice was observed 1, 3, 7, 14, and 21 d after the injection through fluorescence tracing and in vivo imaging. Accordingly, the clinical SVF injection regimens were optimized based on the experimental result of mice. Finally, local SVF injection was performed on different frequencies for patients in different wound conditions, with the efficacy being observed. Results:The fluorescence of SVF was observed from the tissue slices of the acute injury, chronic injury, and negative control groups 14 d post-injection. The result showed that the fluorescence intensity of SVF 1, 3, and 7 d post-injection was in the order of the negative control group > the acute injury group > the chronic injury group. The acute injury group ranked at the top and the chronic injury group remained at the bottom 14 d after the injection. The fluorescence of SVF in each group was barely detected 21 d after the injection. Compared to the negative control group, the acute injury group exhibited statistical differences only 14 d post-injection ( t = 4.11, P < 0.05), while the chronic injury group displayed statistical differences 1, 3, 7, and 14 d after the injection ( t = 3.88-5.74, P < 0.05). Furthermore, the acute injury group exhibited significantly higher fluorescence intensity of SVF than the chronic injury group ( t = 4.73-8.38, P < 0.05). The half-life of SVF for the negative control, acute injury, and chronic injury groups was 6.336, 6.014, and 2.163 d, respectively. As indicated by the application of SVF transplantation based on traditional surgical protocols in the clinical trial, SVF can significantly promote wound repair, with earlier SVF transplantation being more beneficial for wound healing. Conclusions:The conversion of SVF differs in the microenvironments of acute and chronic radiation-induced skin injuries. This can serve as an essential guide for the administration timing and injection frequency of SVF in clinical applications.

Clinical trials of drugs for rare diseases face special challenges such as a limited number of patients,difficult recruitment,long trial period,and frequent video interviews during the trial.Therefore,in the clinical operation of rare diseases,a decentralized clinical trials(DCT)model based on the"patient-cen-tred"research and development concept is implemented.With the help of decentralized elements and digital health technology,the barriers of geographical restrictions can be overcome and subjects do not have to be limit-ed to traditional clinical trial sites(hospitals/research centers),which can significantly reduce the burden on subjects,increase their representation,and obtain a wider range of scientific research data.To guide the indus-try's scientific and standardized application of DCT in the research and development of drugs for rare diseases,the Center for Drug Evaluation of the National Medical Products Administration(NMPA)organized the stake holders to draft the Technical Guideline for the Application of Decentralized Clinical Trials in the Research and Development of Drugs for Rare Diseases.This guideline provides scientific recommendations for the development and implementation of DCT for rare disease drugs.It aims to solve the difficult and key problems during rare disease drug research and development,improve the efficiency and optimize patient experience.This article,combining the research and development concepts in the guideline,explains the current research and develop-ment thinking on the application of DCT in the research and development of rare disease drugs,with a view of providing reference for the industry.

Objective: To investigate the changes of microorganisms and metabolites in joint effusion of patients with Rheumatoid arthritis(RA), Osteoarthritis(OA) and Urarthritis(UA). To provide new ideas for the study of the effect of microbiota on the pathogenesis of arthritis. Methods: Joint effusion samples were collected from 20 patients with RA, 20 patients with OA, and 20 patients with UA. 16S rRNA gene sequencing and untargeted ultra-high performance Liquid chromatography-mass spectrometry(LC-MS) were used to explore the differences in microorganisms and metabolites among the three groups. Pearson correlation analysis was used to detect the correlation between effusion microbiota and metabolites. Results: There were differences in microbial diversity and microbiota composition among the three groups. Combined with VIP>1 from OPLS-DA andP<0.05 from two-tailed Students t-test, 45 differential metabolites(Between RA and OA groups), 38 differential metabolites(Between UA and OA groups) and 16 differential metabolites(Between RA and UA groups), were identified. GO analysis and KEGG pathway analysis showed that the differential metabolic pathways among the three groups were mainly concentrated in citric acid cycle(TCA cycle), nucleotide metabolism, amino acid metabolism and glycolysis pathway. Correlation analysis of joint effusion microbiota and metabolites suggested that bacteria enriched in the three groups of joint effusion, such asPrevotella,Clostridium ruminosus,Prevotellaceae＿UCG-001, were related to many key metabolites such as lysozyme, uric acid, glucose, and L-glutamine. Conclusion This study shows that there are a variety of bacterial flora in joint cavity effusion of RA, OA, and UA patients, and the differential metabolites produced by them are involved in the pathogenesis of the three types of arthritis by affecting a variety of metabolic pathways.

Objective To investigate the effect and mechanism of tetramethylpyrazine(TMP)on cognitive function in mice with post-traumatic stress disorder(PTSD).Methods The mice were randomly divided into normal group,model group and experimental group.Except for the normal group,the PTSD mouse model was established by single prolonged stress(SPS).The experimental group was intraperitoneally injected with 10 mg·kg-1 TMP,and the normal group and the model group were intraperitoneally injected with an equal amount of 0.9％NaCl.The Morris water maze,open field and elevated plus maze tests were used to evaluate the cognitive behavior of the mice.The apoptosis of neurons was detected by Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL).The expression of ionized calcium binding adapter molecule-1(Iba-1)protein was detected by immunofluorescence(ICC).The content of oxidative stress inflammatory factors was detected by enzyme-linked immunosorbent assay(ELISA).Results The escape latency of the normal group,model group,and TMP group were(56.50±9.89),(87.16±10.48)and(68.63±10.19)s,respectively;the corner residence time of the open field were(190.37±40.64),(260.39±40.54)and(218.63±38.27)s,respectively;the apoptosis rates were(18.28±2.35)％,(39.36±3.65)％and(30.74±3.58)％,respectively;the fluorescence intensities of Iba-1 were(8.01±2.23)％,(50.87±7.31)％and(7.49±1.41)％;malondialdehyde contents were(5.46±0.95),(12.98±2.06)and(8.31±1.28)nmol·mg-1,respectively;tumor necrosis factor-α contents were(53.59±9.91),(115.46±11.53)and(74.38±10.77)pg·mL-1,respectively.The above indexes in the normal group and the experimental group were statistically significant compared with the model group(P＜0.05,P＜0.01).Conclusion TMP can improve the cognitive function of PTSD mice,and the mechanism may be related to the regulation of inflammation and oxidative stress.

Objective:To explore the effects of depressive symptoms on sleep quality in adolescents with depressive disorder, and the mediating roles of cognitive fusion and sleep belief.Methods:A sample of 210 adolescents with first episode depressive disorder aged 12-18 years were recruited to complete 17-item Hamilton depression scale (HAMD-17), Pittsburgh sleep quality index (PSQI), cognitive fusion questionnaire (CFQ), and dysfunctional beliefs and attitudes about sleep scale (DBAS-16) from November 2021 to July 2022. SPSS 26.0 software was used to perform descriptive analysis and correlation analysis. The mediating effect was tested by Bootstrap analysis using PROCESS V 3.4 Macro program.Results:The incidence of low sleep quality in adolescents with depressive disorder was 69.0%(145/210). HAMD-17 score was (22.4±7.9), PSQI score was (9.7±3.7), CFQ score was (51.6±7.8), DBAS-16 score was (43.5±8.4).PSQI was positively correlated with the scores of HAMD-17 and CFQ( r=0.613, 0.463, both P<0.001).HAMD-17 was positively correlated with CFQ score ( r=0.488, P<0.001).DBAS-16 was negatively correlated with scores of PSQI, HAMD-17 and CFQ( r=-0.326, -0.284, -0.354, all P<0.001). The direct effect of depression on sleep quality was 0.230(95% CI=0.169-0.293). The indirect effect of depression on sleep quality through two pathways, the separate mediating effect value of cognitive fusion was 0.041 (95% CI=0.011-0.074), and the chain mediating effect value of cognitive fusion and sleep beliefs was 0.008(95% CI=0.001-0.020). Conclusion:Depressive symptoms can directly affect sleep quality of depressive disorder adolescents and indirectly through cognitive fusion and sleep beliefs.