Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Professor ZHOU Peng has deeply discussed the pathological characteristics of psoriasis vulgaris,emphasizing that the disease is usually manifested deficiency interweaved with excess,leading to frequent recurrence and persistent refractory,which may lead to psychological and emotional problems of patients.This paper further expounds the effect of blood stasis on the pathogenesis,progression and prognosis of psoriasis,and puts forward a new method of combining Lingnan fire needling and filiform needling acupuncture technique to treat psoriasis vulgaris with blood stasis syndrome.Professor ZHOU Peng believes that the treatment principle of this disease is"regulating the mind first,rectifying blood as a base,syndrome differentiating and eliminating pathogenic factors",aiming at comprehensively considering the etiology and symptoms,in order to achieve more effective treatment results.Combined with the analysis of dermoscopic signs,it provides a possible improvement direction for the treatment of psoriasis vulgaris from a new perspective.

Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.

Background::China is one of the countries with the largest burden of gastrointestinal and liver diseases (GILD) in the world. The GILD constitutes various causes of mortality and disability. The study aimed to investigate the trend of GILD in China using the Global Burden of Diseases Study 2019 (GBD 2019) data resources from 1990 to 2019.Methods::The data on the age-standardized mortality rates (ASMR) and disability-adjusted life years (DALYs) for GILD in China from 1990 to 2019 were collected from the GBD 2019 data resources. Furthermore, the ranking of the main causes of deaths and DALYs, as well as the trends of ASMR, DALYs, years of life lost (YLLs), and years of life lost due to disability (YLDs) per 1,000,000 in GILD were reported.Results::The ASMR and DALYs for stomach cancer, liver cancer, and esophageal cancer, which ranked top three among the GILDs from 1990 to 2019, were gradually decreasing. Significant decreases in the ASMR and DALYs were found in diarrheal diseases and acute hepatitis (A, E, and C). However, noteworthy increases were found in those of colon and rectum cancer (CRC) and pancreatic cancer. Trend of DALYs, mortality, and YLLs rates for most of GILD were decreasing from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trend. The DALYs, mortality and YLLs of most GILD diseases showed decreasing trends from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trends.Conclusions::The result of the GBD 2019 showed that the rates of most GILDs decreased in China; however, gastrointestinal and liver cancer, such as stomach cancer still held the top ranking. Furthermore, the shift from infectious diseases to non-communicable causes among GILD burden is occurring.

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.
Mice ; Animals ; Alocasia/metabolism* ; MAP Kinase Signaling System ; Caspase 3/metabolism* ; Apoptosis ; RNA, Messenger/metabolism*

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Background::Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer.Methods::Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. Results::lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. Conclusion::Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.

In the process of seeking new strategies to improve the efficacy of antidepressants,traditional Chinese medicine inter-vention has gradually revealed its unique prevention and treat-ment advantages.The dopamine reward system is closely in-volved in the pathological occurrence and development of depres-sion.Currently,research has mostly focused on the functional mechanism of a specific nucleus in the dopamine reward system,and there is less research focused on the functional mechanism of the neural circuit.In the current micro research on reward cir-cuits,the association between abnormal reward circuits and neg-ative emotions such as anxiety and depression has been widely recognized.Traditional Chinese medicine intervention can exert antidepressant effects by influencing reward circuits.This article provides a review on the loop mechanism of dopamine reward system involvement in depression and research on traditional Chinese medicine intervention.

Carpal tunnel syndrome (CTS) is a condition caused by compression of the median nerve in carpal canal. In recent years, due to popularity of electronic devices such as computers, the incidence of CTS has shown a rapid rising trend. Its treatment methods include surgical treatment and conservative treatment. For mild to and moderate CTS, conservative treatment is preferred. Acupotomy, as an innovative and unique treatment method, could relieve pressure in carpal canal by releasing transverse ligament of wrist and promote local blood circulation to treat CTS, and has characteristics of less trauma, short course of treatment and low cost, which is more acceptable to patients. In addition, the combination of needle-knife and other therapies also has a good effect. However, traditional needle-knife therapy has certain limitations in operation, and its safety problems can be effectively solved with the help of ultrasound technology. Therefore, ultrasus-guided needle-knife therapy for CTS has become a current research hotspot, but its long-term therapeutic effect still needs to be further verified.
Humans ; Carpal Tunnel Syndrome/therapy* ; Acupuncture Therapy/methods*