The pathogenesis of osteoarthritis (OA) is related to a variety of factors such as mechanical overload, metabolic dysfunction, aging, etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.

Objective To investigate the effects of emodin on the healing of infected wound and the regulation of Toll-likereceptor 4(TLR4)/nuclear factor kappa-B(NF-κB)signaling pathway in rats.Methods The model of infectious wounds rats were constructed by the full-thickness skin defect method.The successful model rats were randomly divided into model group,control group and experimental-L,-M,-H groups with 12 rats per group;another 12 normal rats were taken as the normal group.Experimental-L,-M,-H groups was applied with emodin 150,300 and 600 μg·d-1 and 200 mg·kg-1 emodin by gavage,respectively.Control group was applied with mopirolacin cream 0.1 g·d-1 on rat wounds,once a day.Normal and model groups were treated with 0.9％NaCl.Six groups were treated for 21 days.The wound healing rates and dynamic blood flow were measured.The levels of tumor necrosis factor(TNF)-α and interleukin(IL)-1β in serum and the hydroxyproline(HYP)and catalase(CAT)in wound tissue were measured by enzyme linked immunosorbent assay.The protein levels of TLR4 and NF-κB in wound were determined by Western blot.Results The wound healing rates of experimental-M,-H groups,control group and model group were(50.70±1.26)％,(75.51±0.50)％,(69.44±1.65)％and(28.58±5.09)％,respectively.The dynamic blood flow values of experimental-M,-H groups,control group,model group and blank group were(123.71±3.71),(155.61±2.47),(146.29±2.04),(79.47±4.76)and(158.00±1.93)mL·min-1;the levels of TNF-α were(81.05±2.32),(56.69±1.59),(69.53±2.39),(139.46±2.46)and(46.49±5.71)ng·L-1;the levels of IL-1β were(59.87±0.83),(42.66±1.30),(48.37±3.34),(88.79±1.84)and(33.93±2.19)ng·L-1;the levels of HYP were(24.79±0.82),(31.12±1.16),(25.83±1.12),(16.88±2.20)and(32.95±1.18)pg·mg-1;the levels of CAT were(24.99±1.47),(34.52±1.26),(31.00±1.15),(13.70±2.09)and(34.23±0.70)U·mg-1;the relative expression levels of TLR4 protein were 0.74±0.05,0.53±0.05,0.55±0.04,1.09±0.07 and 0.23±0.05;the relative expression levels of NF-κB protein were 0.69±0.06,0.44±0.04,0.52±0.03,1.10±0.04 and 0.22±0.10,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups were statistically significant(all P＜0.05).Conclusion Emodin can improve the infectious wound healing and dynamic blood flow in rats,and inhibit the inflammatory levels and oxidative stress response in wound tissue,and the mechanism may be related to the regulation of TLR4/NF-κB pathway.

Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.

Objective:To analyze the changes in the disease burden of prostate,testis,kidney and bladder cancers among uri-nary and reproductive system tumors in Chinese men from 1990 to 2019 with a prediction of the future trend.Methods:We re-trieved the data on the incidence,mortality and disease burden of prostate,testis,kidney and bladder cancers in Chinese men between 1990 and 2019 from the database of Global Burden of Disease Study 2019.Using the Joinpoint regression model,we analyzed the trend of changes in the disease burden,and predicted the prevalence of the tumors with the ARIMA model.Results:From 1990 to 2019,the standardized incidence and prevalence of prostate,testis,kidney and bladder cancers were on the rise in Chinese men,and those of testis cancer increased most significantly,by 326.79% and 1070.93% respectively.The disease burden of PCa was the highest,with standardized incidence,prevalence and mortality ratios of 17.34/100 000,117.65/100 000 and 7.79/100 000 respectively in 2019.The standardized mortality and disability-adjusted life years(DALY)of kidney cancer were increased by 103.59% and 103.17% respectively.The highest incidence,mortality and DALY of prostate,kidney and bladder cancers in 2019 were found in 90-94 years old males,the highest prevalence rates of prostate,kidney and bladder cancers in the 70-89-year-olds,and the highest prevalence of testis cancer in the25-49-year-olds.ARIMA model prediction showed that the standardized incidence rates of prostate,testis,kidney and bladder cancers in Chinese men kept rising from 2020 to 2029.Conclusion:The disease burden of prostate,tes-tis,kidney and bladder cancers in Chinese men is on the rise,and their standardized incidence rates will be even higher by 2029,with a significant increase in the disease burden in young men,which suggests the need of more attention to the prevention and treatment of genitourinary system tumors in young males.

Background/Aims: Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR). Methods: This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR. Results: The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5–40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7–67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1–62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12–2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21–0.81). Conclusions Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

To design a treatment plan for patients with epididymal obstruction, we explored the potential impact of factors such as body mass index (BMI) and age on the surgical outcomes of vasoepididymostomy (VE). In this retrospective study, 181 patients diagnosed with obstructive azoospermia (OA) due to epididymal obstruction between September 2014 and September 2017 were reviewed. All patients underwent single-armed microsurgical intussusception VEs with longitudinal two-suture placement performed by a single surgeon (KH) in a single hospital (Peking University Third Hospital, Beijing, China). Six factors that could possibly influence the patency rates were analyzed, including BMI, age, mode of anastomosis, site of anastomosis, and sperm motility and quantity in the intraoperative epididymal fluid. Single-factor outcome analysis was performed via Chi-square test and multivariable analysis was performed using logistic regression. A total of 159 (87.8%, 159/181) patients were followed up. The follow-up time (mean ± standard deviation [s.d.]) was 27.7 ± 9.3 months, ranging from 12 months to 48 months. The overall patency rate was 73.0% (116/159). The multivariable analysis revealed that BMI and age significantly influenced the patency rate (P = 0.008 and 0.028, respectively). Younger age (≤28 years; odds ratio [OR] = 3.531, 95% confidence interval [95% CI]: 1.397-8.924) and lower BMI score (<26.0 kg m^-2; OR = 2.352, 95% CI: 1.095-5.054) appeared to be associated with a higher patency rate. BMI and age were independent factors affecting the outcomes of microsurgical VEs depending on surgical expertise and the use of advanced technology.
Humans ; Male ; Adult ; Retrospective Studies ; Body Mass Index ; Epididymis/surgery* ; Vas Deferens/surgery* ; Treatment Outcome ; Sperm Motility ; Microsurgery ; Surgeons ; Vasovasostomy

N⁶-methyladenosine (m⁶A) is a ubiquitous RNA modification in mammals. This modification is "written" by methyltransferases and then "read" by m⁶A-binding proteins, followed by a series of regulation, such as alternative splicing, translation, RNA stability, and RNA translocation. At last, the modification is "erased" by demethylases. m⁶A modification is essential for normal physiological processes in mammals and is also a very important epigenetic modification in the development of cancer. In recent years, cancer-related m⁶A regulation has been widely studied, and various mechanisms of m⁶A regulation in cancer have also been recognized. In this review, we summarize the changes of m⁶A modification in prostate cancer and discuss the effect of m⁶A regulation on prostate cancer progression, aiming to profile the potential relevance between m⁶A regulation and prostate cancer development. Intensive studies on m⁶A regulation in prostate cancer may uncover the potential role of m⁶A methylation in the cancer diagnosis and cancer therapy.
Animals ; Male ; Humans ; Methylation ; Adenosine/metabolism* ; RNA/metabolism* ; Methyltransferases/metabolism* ; Prostatic Neoplasms ; Mammals

Chronic stress leads to many psychiatric disorders, including social and anxiety disorders that are associated with over-activation of neurons in the basolateral amygdala (BLA). However, not all individuals develop psychiatric diseases, many showing considerable resilience against stress exposure. Whether BLA neuronal activity is involved in regulating an individual's vulnerability to stress remains elusive. In this study, using a mouse model of chronic social defeat stress (CSDS), we divided the mice into susceptible and resilient subgroups based on their social interaction behavior. Using in vivo fiber photometry and in vitro patch-clamp recording, we showed that CSDS persistently (after 20 days of recovery from stress) increased BLA neuronal activity in all the mice regardless of their susceptible or resilient nature, although impaired social interaction behavior was only observed in susceptible mice. Increased anxiety-like behavior, on the other hand, was evident in both groups. Notably, the CSDS-induced increase of BLA neuronal activity correlated well with the heightened anxiety-like but not the social avoidance behavior in mice. These findings provide new insight to our understanding of the role of neuronal activity in the amygdala in mediating stress-related psychiatric disorders.
Amygdala ; Animals ; Anxiety/etiology* ; Anxiety Disorders ; Avoidance Learning ; Mice ; Mice, Inbred C57BL ; Social Behavior ; Stress, Psychological/complications*

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ² test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.
Colectomy ; Colonic Neoplasms/surgery* ; Female ; Humans ; Laparoscopy ; Male ; Prognosis ; Propensity Score ; Retrospective Studies ; Robotic Surgical Procedures ; Treatment Outcome