Objective:To explore the diagnostic value of motion pain induction test for early knee osteoarthritis.Methods:A cross-sectional study was conducted and the data came from The Project of Health Management of Knee osteoarthritis in Community in Hangzhou in 2018, and a total number of 1 816 people were included which were divided into normal group ( n=530), early group ( n=534) and middle-late group ( n=752) by not sick, sick while Kellgren-Lawrence (KL) ≤Ⅱ and sick while KL>Ⅱ starting, squatting, walking up and down stairs and doing housework were included in the test, and the statistical indicators included age, gender and pain scores (visual analogue scale, VAS). Receiver operating characteristic (ROC) curves were mapped after the correlation analysis to obtain the cut-off points and compare their values of area under the curve (AUC). The confounders which included age and gender were corrected by propensity score matching (PSM) and the balance test is consistent with P>0.05 after the PSM. The Kappa analysis was used to verify the consistency of two diagnostic methods. Results:The age of normal, early and medial-late groupwas 67.39±7.43, 67.41±9.52, 71.55±9.87. And the gender distribution of three groups was (238 male, 292 female), (209 male, 325 female), (357 male, 395 female). There was no heterogeneitybetween the normal group and early group in distribution ( P>0.05) while there was heterogeneity between the early and medial-late group ( t=-0.034, P<0.05; χ2=8.80, P<0.05). The VAS scoresof starting pain in three groups was 0.16±0.37,2.70±1.69, 3.68±2.10. The VAS scoresof squatting pain was 0.42±0.49, 2.88±1.44, 4.01±2.08. The VAS scoresof up and down stair pain was 0.47±0.50, 2.87±1.38, 3.82±1.98. The VAS scoresof housework pain was 0.14±0.35, 2.15±1.40, 3.45±2.09. The VAS scoresofmaximum pain was 0.51±0.50, 3.59±1.48, 4.68±2.01. And there was significant difference between normal and early groupin all kinds of pain ( t=-33.81; t=-37.25; t=-37.66; t=-32.07; t=-45.41; P<0.05). The difference between early and medial-late group in all type of pain was significant ( t=-8.93; t=-10.84; t=-9.56; t=-12.52; t=-10.64; P<0.05). The results were similar after adjusting for confounders except for the pain of starting ( P>0.05). The results of ROC curve between normal and early group showed the maximum pain's AUC point was 0.98 and larger than others, and its cut-off point was 1. After adjusted, the results of ROC curve between early and medial-late group showed the maximum pain's AUC point was 0.72 which was larger than others and cut-off point was 4. For the AUC of ROC curve between early and medial-late groupwas lower, Kappa-test was used, and the Kappa point of two diagnostic methods was 0.41 ( P<0.05). Conclusion:The maximum of pain score in pain dimension>1 and ≤ 4 could be preliminarily diagnosed as early KOA. It had high value in separating early KOA from normal people and approximately similar to X-ray, and the value of identifying early and mid-late KOAwas moderateas well as the moderate consistency with KL stage. Comprehensive judgment of imaging examination should be improved when conditions are available.

Objective To explore the efficacy and tolerance of adverse reactions of gene detection technique in guiding individualized targeted therapy for advanced metastatic renal cell carcinoma.Methods Retrospective analysis was performed on the clinical data of 62 patients with advanced metastatic renal cell carcinoma before and after receiving targeted drug treatment in our department from October 2015 to October 2017.Among the 62 patients,there were 36 males and 26 females,with an average age of (54 ± 13) years old.16 patients were treated with sunitinib,20 patients were treated with sorafenib and 26 patients were treated with pazopanib.A total of 28 patients (individualized group) were selected to receive targeted drug according to the results of gene detection,and 34 patients were treated with targeted drug empirically (empirical group).In individualized group,there were 17 males and 11 females with the average age of (51.3 ± 15.6) years old.20 patients accepted the operation.The distant metastasis included bone metastasis in 21 cases,lung metastasis in 7 cases,liver metastasis in 16 cases,epidermal metastasis in 4 cases and lymphatic metastasis in 14 cases.According to risk of MSKCC,the case number of low risk,moderate risk and high risk were 15,7,6,respectively.7 patients were treated with sunitinib,8 patients were treated with sorafenib and 13 patients were treated with pazopanib.In empirical group,there were 19 males and 15 females with the average age of (56.3 ± 10.1) years old.22 patients accepted the operation.The distant metastasis included bone metastasis in 20 cases,lung metastasis in 5 cases,liver metastasis in 13 cases,epidermal metastasis in 3 cases and lymphatic metastasis in 15 cases.According to risk of MSKCC,the case number of low risk,moderate risk and high risk were 20,g,6,respectively.9 patients were treated with sunitinib,12 patients were treated with sorafenib and 13 patients were treated with pazopanib.The baseline characteristics of the two groups of patients,including gender,age,whether operation was performed,site of metastasis,and risk of MSKCC,didn't show significant difference.Patients in both groups received the standard treatment regimen and the follow-up duration was 4-26 months to observe the efficacy,progression-free survival and tolerance to adverse reactions of the targeted therapy.Results After 12 months of treatment,15 patients in the individualized group was recorded objective remission.7 patients in the empirical group was recorded objective remission,as well.The tumor control efficacy of the individualized group was significantly better than that of the empirical group (46.4％ vs.20.6％,P =0.03).Meanwhile,the median progression-free survival time (15.2 months,3.7-24.2 months) in the individualized group was significantly longer than that in the empirical group (12.1 months,2.8-22.1 months) (P =0.009).Compared with the empirical group,the higher incidence of targeted treatment-related adverse reactions occurred in the individualized group,including thrombocytopenia (46.4％ vs.17.6％ P =0.014),leukopenia (46.4％ vs.17.6％ P =0.005),hypertension (71.4％ vs.44.1％,P =0.031) and hypothyroidism(60.7％ vs.29.4％,P=0.013).Conclusions Compared with the patients with empirical drugs,the application of gene detection technique to select individualized targeted drugs for the treatment of advanced metastatic renal cancer is obvious curatively effective,and to a certain extent extends the progression-free survival time of patients.

Chondroitin sulfate (CS) is a sulfurated glycosaminoglycan, a major component of the extracellular matrix, widely distributed in skin, cartilage and vascular tissue. CS plays an important role in the physiological state regulation of articular cartilage, which affects tensile strength and elasticity of tissues by influencing aggrecan. Previous studies have shown that CS sulfate modification may be related to the growth and development disorders of cartilage tissue and the occurrence of osteoarticular diseases. At the same time, CS is also a common joint supplement, often used in the treatment of osteoarthritis and Kashin-Beck disease. In this paper, the research progress of CS sulfate modification characteristics in Kashin-Beck disease and osteoarthritis and the application of the preparation in the treatment of Kashin-Beck disease and osteoarthritis are reviewed, aiming to provide help for the investigation of the etiology of Kashin-Beck disease and the treatment of osteoarthritis and Kashin-Beck disease.

Objective To explore the effect of miR-1-3p on the malignant biological behavior of human esophageal squamous cell carcinoma cells and the potential mechanisms.Methods The Gene Expression Omnibus(GEO)database was analyzed to screen differentially expressed miRNAs in esophageal squamous cell carcinoma(ESCC).qRT-PCR was used to detect the expression of miR-1-3p in human ESCC cell lines(KYSE30,KYSE150,KYSE410,KYSE510,and Eca109)and normal esophageal epithelial cell line HET-1A.CCK-8,wound healing,Transwell assays,and flow cytometry were applied to detect the effect of miR-1-3p on the proliferation,migration,invasion,and apoptosis of ESCC cells.Bioinformatics tool was used to predict the target genes of miR-1-3p.A Kaplan-Meier survival curve was drawn to analyze the correlation between STC2 expression and overall survival of patients in the ESCC cohort of the TCGA database.Fluorescence in situ hybridization was performed to verify the subcellular location of miR-1-3p in ESCC cells,and dual-luciferase reporter gene assay was performed to validate the regulation of miR-1-3p on stanniocalcin 2(STC2).RNA immunoprecipitation assays were used to detect the binding of miR-1-3p and STC2.Western blot assay was performed to determine the effect of miR-1-3p on the expression of STC2 and endoplasmic reticulum stress pathway-related proteins,including p-PERK,p-eIF2α,and ATF4.CCK-8,wound healing,Transwell assays,and flow cytometry were applied to detect the effect of STC2 overexpression and knockdown on the proliferation,migration,invasion,and apoptosis of ESCC cells.Results The expression of miR-1-3p was lower in ESCC cell lines than in HET-1A cells(all P<0.05).The transfection of miR-1-3p mimic decreased the proliferation,invasion,and migration of ESCC cells(all P<0.05)and promoted the apoptosis of ESCC cells(all P<0.001).Bioinformatics tool showed that STC2 was a target gene of miR-1-3p.The expression of STC2 in ESCC tissues was higher than that in normal esophageal epithelial tissues in the ESCC cohort of TCGA database and was negatively correlated with prognosis(all P<0.05).miR-1-3p was located in the cytoplasm and can directly bind to STC2 mRNA.The transfection of miR-1-3p mimic downregulated the expression of STC2,p-PERK,p-eIF2α,and ATF4(all P<0.05).The overexpression of STC2 promoted the proliferation,invasion,and migration(all P<0.05)and inhibited the apoptosis of ESCC cells(all P<0.05).Knockdown of STC2 inhibited the proliferation,invasion,and migration(all P<0.05)and promoted the apoptosis of ESCC cells(all P<0.05).Conclusion miR-1-3p inhibits the malignant biological behavior and promotes the apoptosis of esophageal squamous cell carcinoma cells by regulating STC2 possibly by suppressing the endoplasmic reticulum stress.

Objective:To investigate the effects of long non-coding RNA (lncRNA) Gm13568 on the activation of A1 astrocytes and the progress of experimental autoimmune encephalomyelitis (EAE) in mice.Methods:A recombinant lentiviral vector (LV-Inhibit-Gm13568) carrying astrocyte-specific promoter of glial fibrillary acidic protein (GFAP) was established to inhibit the function of endogenous Gm13568. A control vector (LV-ctrl) was established as well. The recombinant vectors were packaged. C57BL/6 mice were injected with 1×10 7 transforming units of viral suspension via the tail vein and 7 d after the injection, myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55) was used to establish the mouse model of EAE. Four groups, PBS group, EAE group, LV-ctrl+ EAE group and LV-Inhibit-Gm13568+ EAE group, were included in this study. Clinical signs of the mice were monitored daily in a double-blinded manner. The mice were sacrificed 23 d after the EAE model was established and the spinal cord tissues were collected. The expression of Serping 1, C3, Srgn and H2-T23 at mRNA level was detected by real-time PCR. Changes in the expression of IL-6, TNF-α, macrophage chemotactic protein-1 (MCP-1) and interferon-inducible protein-10 (IP-10) were measured. Western blot was used to investigate the expression of GFAP and Notch1 in spinal cord tissues and the phosphorylation of signal transduction and transcription activator 3 (STAT3). The expression of Notch1 intracellular domain (NICD) and GFAP in spinal cord tissues was detected by immunofluorescence. Furthermore, the infiltration of inflammatory cells and the demyelination of spinal cord were observed using HE and Luxol fast blue (LFB) staining methods. Results:Compared with PBS group, A1 astrocytes were activated and Notch1 expression was significantly up-regulated in EAE group and LV-ctrl+ EAE group. The clinical score of mice in LV-Inhibit-Gm13568+ EAE group was decreased from an average score of 3.5 to less than 1 on 23 d after antigen induction and the clinical symptoms were alleviated as compared with the mice in LV-ctrl+ EAE group. Meanwhile, the activation of A1 astrocytes was down-regulated, and the production of inflammatory cytokines and chemokines was also reduced. The expression of Notch1, GFAP and NICD at protein level and the phosphorylation of STAT3 were significantly reduced. Moreover, the infiltration of inflammatory cells and demyelination of spinal cord tissues were alleviated significantly.Conclusions:LncRNA Gm13568 might regulate the activation of A1 astrocytes via the Notch1/STAT3 pathway, thus affecting the production of inflammatory cytokines and chemokines and participating in the process of EAE.

Background With urbanization and residential space expansion, ecological environment and human health issues have become hot social topics. Forest health, as a way of seeking health in nature, has begun to receive public attention in the context of the gradually increasing sub-healthy population and various psychological and physical diseases at a young age. Objective To systematically evaluate the effects of forest therapy on selected physical and mental health indicators. Methods Relevant research literature was retrieved from domestic and international databases (China National Knowledge Infrastructure, Wanfang Database, China Biomedical Literature Service System, Web of Science, ScienceDirect, PubMed, Embase, and Cochrane Library), with a time range from database establishment to January 31, 2023. Relevant data were extracted for meta-analysis to explore the relationship between forest therapy and selected psychological and physiological indicators. Results A total of 85 articles were included, and the meta-analysis results showed that better scores of Profile of Mood States, Positive and Negative Affect Scale, Beck Depression Inventory, and State Trait Anxiety Scale were found in the forest group than those in the urban group (P<0.05); the levels of systolic blood pressure, diastolic blood pressure, heart rate, sympathetic nerve indicator [ln (LF/HF)], salivary cortisol, and serum inflammatory factors were lower in the forest group than in the urban group, while parasympathetic nerve indicator [ln (HF)] level was higher in the forest group than in the urban group (P<0.05). The results of subgroup analysis showed that the changes in heart rate (SMD=−1.62, 95%CI: −2.41, −0.82), ln (HF) (SMD=1.29, 95%CI: 0.73, 1.85), ln (LF/HF) (SMD=−1.49, 95%CI: −2.13, −0.86), and salivary cortisol (SMD=−0.53, 95%CI: −0.81, −0.25) were more significant when the duration of forest therapy was ≤ 0.5 h, the recovery effect on emotional state was better in the >0.5~3 h group (such as tension SMD=−2.40, 95%CI: −3.21, 1.59), and the reduction effects on systolic blood pressure (SMD=−0.53, 95%CI: −1.03, −0.03) and diastolic blood pressure (SMD=−0.42, 95%CI: −0.88, 0.04) were better in the >3 h group. Seated meditation showed better recovery effects on multiple indicators of Profile of Mood States (such as fatigue SMD=−2.26, 95%CI: −3.07, −1.45), while walking showed better recovery effects on physiological indicators such as blood pressure (systolic blood pressure SMD=−0.57, 95%CI: −1.07, −0.06; diastolic blood pressure SMD=−0.72, 95%CI: −1.36, −0.07) and heart rate (SMD=−1.51, 95%CI: −2.38, -0.64). Except for blood pressure, the health benefits of forest therapy in the younger age group were generally better than those in the middle-aged and elderly group. Conclusion Relaxed and comfortable psychological feeling is reported when practicing forest therapy; it can lower blood pressure and heart rate, regulate the autonomic nervous system; it can also reduce the release of stress hormones and lower serum levels of inflammatory factors, exerting an auxiliary recovery effect on cardiovascular and immune system disorders. At the same time, the therapy duration, form, and age of the subjects have a certain impact on the effects of forest therapy practice.

Myelodysplastic syndrome (MDS) is a malignant hematologic tumor, which is currently difficult to cure. The theory of Xuanfu was proposed by Liu Wansu, which is unique in the clinical evidence of Chinese medicine and is less frequently applied to hematological diseases. The application of Xuanfu theory in myelodysplastic syndrome provides new ideas for the treatment of the disease. The abnormal flow of Qi, blood and fluids caused by the occlusion of the Xuanfu is the cause of toxic stasis obstruction, which is the pathogenesis of toxic stasis obstruction. Thus, the method of dispersion of Bone from Xuanfu, the external treatment of Xuanfu, and regulation of liver qi and Xuanfu help to return to normal of opening and closing function of Xuanfu, and release toxic stasis. In this paper, we analyzed the evidence of toxin-stasis obstruction in myelodysplastic syndrome from the theory of Xuanfu, aiming to provide a feasible theoretical basis for clinical treatment of the disease.

ObjectiveTo evaluate the efficacy and safety of various oral Chinese patent medicines in the adjuvant treatment of chronic prostatitis/chronic pelvic pain syndrome （CP/CPPS） based on network Meta-analysis. MethodRandomized controlled trials （RCTs） of oral Chinese patent medicine in the adjuvant treatment of CP/CPPS were retrieved from the databases of China National Knowledge Infrastructure （CNKI）， Wanfang， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science from database inception to November， 2022. The quality of the included literature was evaluated according to the Cochrane risk-of-bias tool， and the data were analyzed by RevMan 5.4 and Stata 16 software. ResultA total of 63 RCTs were included， with 13 kinds of oral Chinese patent medicines involved， including Qianlie Shutong capsules， Ningmitai capsules， Qianlie Beixi capsules， Sanjin tablets， etc. The results of the network Meta-analysis showed that in terms of clinical effective rate， the intervention measure ranked first was Qianlie Beixi capsules combined with conventional western medicine. In terms of reducing pain， the intervention measure ranked first was Sanjin tablets combined with conventional western medicine. In terms of reducing urination disorder， the intervention measure ranked first was Relinqing granules combined with conventional western medicine. In terms of improving quality of life， the intervention measure ranked first was Qianlie Beixi capsules combined with conventional western medicine. In terms of reducing the total National Institutes of Health Chronic Prostatitis Symptom Index （NIH-CPSI） score， the intervention measure ranked first was Yinhua Miyanling tablets combined with conventional western medicine. In terms of reducing leukocyte count in prostatic secretions， the intervention measure ranked first was Qianlie Jiedu capsules combined with conventional western medicine. In terms of safety， the intervention measure with the least adverse reactions was Qianlie Shutong capsules combined with conventional western medicine. The cluster analysis results showed that Qianlie Shutong capsules combined with conventional western medicine had outstanding efficacy and high safety. ConclusionOral Chinese patent medicine in the adjuvant treatment of CP/CPPS can improve the comprehensive efficacy， reduce the NIH-CPSI score and leukocyte count in prostatic secretions， and improve the quality of life of patients. For clinical treatment， the preferred choice is Qianlie Beixi capsules or Qianlie Shutong capsules combined with conventional western medicine. Limited by the quantity and quality of literature included in this study， the results need to be verified by high-quality studies with a larger sample size.

Objective To investigate the articles on liver diseases published by authors from China (excluding Hong Kong, Macao, and Taiwan regions) in Gastroenterology & Hepatology journals indexed in Science Citation Index Expanded (SCIE) in 2016-2020, to analyze the bibliographic and citation data of these articles, and to understand the contribution and impact of Chinese scholars in the field of liver disease research in recent years. Methods The data for bibliometric analysis came from the SCIE database and Journal Citation Reports (JCR). The SCIE database was searched for the journal articles published in JCR Gastroenterology & Hepatology journals in 2016-2020, with a title or abstract containing "Liver", "Hepatocellular", "Hepatitis", "Cirrhosis", or "Hepatic" and a publication type of Article. Clinical guidelines were excluded, and the records with the corresponding author's affiliation containing institutions in China (excluding Hong Kong, Macao, and Taiwan regions) were screened out. R package bibliometrix was used to calculate the frequency of citations of included articles by liver disease studies published by Chinese and global authors in the Gastroenterology & Hepatology journals in 2016-2020, and R package DescTools was used to perform the Cochran-Armitage trend test to observe the change in composition ratio. Results In the Q1 Gastroenterology & Hepatology journals in 2016-2020, liver disease studies published by Chinese authors accounted for 9.5%. In recent years, the proportion of liver disease studies published by Chinese authors in Q1 Gastroenterology & Hepatology journals continues to increase from 6.0% to 12.2% ( P < 0.001). Among the liver disease studies published by Chinese authors in Q1 Gastroenterology & Hepatology journals, 79.7% were funded by National Natural Science Foundation of China, and there was no significant change in the proportion of studies funded by National Natural Science Foundation of China and published by Chinese authors in each partition of Gastroenterology & Hepatology journals in 2016-2020. The frequency of citations of included articles by liver disease studies published by Chinese and global authors in the Gastroenterology & Hepatology journals showed that liver disease studies published by Chinese authors had a high impact in both domestic and international academic communities. Conclusion In recent years, there has been a constant increase in the number of liver disease studies published by Chinese authors in high-impact Gastroenterology & Hepatology journals indexed in SCIE, and most of these studies have been funded by National Natural Science Foundation of China. The liver disease studies published by Chinese authors in Gastroenterology & Hepatology journals have been widely recognized by domestic and international academic communities.