BACKGROUND:Cannabidiol is effective in ameliorating the body's inflammatory response,but no clear mechanistic studies have been conducted to ameliorate skeletal muscle inflammation induced by exhaustive exercise. OBJECTIVE:To explore the mechanism by which cannabidiol improves skeletal muscle inflammation during exhaustive exercise by using transcriptome sequencing technology. METHODS:Thirty-six Sprague-Dawley rats were randomly divided into six groups:blank control group,exercise coconut oil group,exercise control group,50 mg/kg cannabidiol group,60 mg/kg cannabidiol group,and 70 mg/kg cannabidiol group,with six rats in each group.Except for rats in the blank control group,rats in each group were subjected to swimming exercise for 9 days to produce the exhaustive exercise model.At the end of each swimming exercise,rats in the cannabidiol groups were given 2 mL of fat-soluble cannabidiol at different concentrations(50,60,and 70 mg/kg)by gavage;rats in the exercise coconut oil group were given the same volume of coconut oil by gavage until the end of the exercise on the 9th day;and rats in the blank control group and the exercise control group were not given any special treatment.The levels of inflammatory factors and differentially expressed genes in the skeletal muscle of rats in each group were determined using ELISA and transcriptome sequencing techniques.Differentially expressed genes obtained were subjected to KEGG analysis,and the accuracy of the sequencing data was verified by fluorescence quantitative PCR. RESULTS AND CONCLUSION:The results of ELISA showed that the contents of interleukin-6(P<0.05),tumor necrosis factor-α(P<0.01),interleukin-10 and other inflammatory factors in the exercise group increased significantly compared with the blank control group and the coconut oil group.After cannabidiol intervention,the mass concentrations of interleukin-6 and tumor necrosis factor-α showed a sequential decrease with increasing cannabidiol concentration.By comparing GO and KEGG databases,the functional properties of differentially expressed genes were analyzed,and the results showed that the differentially expressed genes were mainly involved in the tumor necrosis factor signaling pathway and the Toll-like receptor signaling pathway.RT-qPCR results showed that the trends of five randomly selected differentially expressed genes were in agreement with the transcriptome sequencing results.To conclude,cannabidiol can improve skeletal muscle inflammation caused by exhaustive exercise.

This paper reports a case of a patient with sleep-related painful erections treated by acupuncture combined with abdominal vibration therapy. The main symptom was repeated painful penile erections during nighttime sleep. The syndrome was differentiated as "water failing to nourish wood" and "liver qi stagnation". Acupuncture was applied at Baihui (GV20), Sishencong (EX-HN1), Guanyuan (CV4), and bilateral Neiguan (PC6), Hegu (LI4), Taichong (LR3), Taixi (KI3), Guilai (ST29), Yongquan (KI1), Yanglingquan (GB34), and Sanyinjiao (SP6). The treatment was combined with abdominal vibration therapy. Treatment was given once daily, five times per week. After the first treatment, the severity and duration of nocturnal erection pain were reduced, and sleep quality was improved. After two weeks of treatment, nocturnal erection pain persisted but became tolerable, with significantly shortened duration.
Humans ; Male ; Acupuncture Points ; Acupuncture Therapy ; Erectile Dysfunction/physiopathology* ; Penile Erection ; Sleep

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

"Weibing" is a fundamental concept in traditional Chinese medicine (TCM), representing a transitional state characterized by diminished self-regulatory abilities without overt physiological or social dysfunction. This perspective delves into the biological foundations and quantifiable markers of Weibing, aiming to establish a research framework for early disease intervention. Here, we propose the "Health Quadrant Classification" system, which divides the state of human body into health, sub-health, disease-susceptible state, and disease. We suggest the disease-susceptible stage emerges as a pivotal point for TCM interventions. To understand the intrinsic dynamics of this state, we propose laboratory and clinical studies utilizing time-series experiments and stress-induced disease susceptibility models. At the molecular level, bio-omics technologies and bioinformatics approaches are highlighted for uncovering intricate changes during disease progression. Furthermore, we discuss the application of mathematical models and artificial intelligence in developing early warning systems to anticipate and avert the transition from health to disease. This approach resonates with TCM's preventive philosophy, emphasizing proactive health maintenance and disease prevention. Ultimately, our perspective underscores the significance of integrating modern scientific methodologies with TCM principles to propel Weibing research and early intervention strategies forward.

B lymphocytes (B cells) play a complex and paradoxical role in tumorigenesis. They can recognize tumor-associated antigens, present these antigens to T cells, and produce antibodies that directly target and eliminate tumor cells. This makes B cells a potentially powerful ally in combating cancer. However, B cells also exhibit immunosuppressive functions, secreting cytokines like IL-10 or generating tumor-promoting antibodies that dampen the anti-tumor immune response, and some tumor cells have even been shown to exploit B cells to promote their growth and metastasis. This dual nature of B cells presents both opportunities and challenges for tumor immunotherapy. In this review, we summarize the mechanisms underlying the multifaceted functions of B cells and their current applications in cancer immunotherapy. Furthermore, we also explore the key issues and future directions in this field, emphasizing the need for further research to fully harness the anti-tumor potential of B cells in the fight against cancer.
Humans ; B-Lymphocytes/immunology* ; Neoplasms/therapy* ; Carcinogenesis/immunology* ; Immunotherapy/methods* ; Animals

As a biocatalyst, laccase has been widely studied and applied in the papermaking industry. However, the low catalytic efficiency and poor stability of natural laccase limit its application in the pulping process. To develop the laccase with high activity and strong tolerance, we carried out directed evolution for modification of the laccase derived from Bacillus pumilus and screened out the mutants F282L/F306L and Q275P from the random mutant library by high-throughput screening. The specific activities of F282L/F306L and Q275P were 280.87 U/mg and 453.94 U/mg, respectively, which were 1.42 times and 2.30 times that of the wild-type laccase. Q275P demonstrated significantly improved thermal stability, with the relative activity 20% higher than that of the wild-type laccase after incubation at 40 ℃, 50 ℃, and 70 ℃ for 4 h. F282L/F306L and Q275P showed greater tolerance to metal ions and organic solvents than the wild-type laccase. The K_m value of the wild-type laccase was 374.97 μmo/L, and those of F282L/F306L and Q275P were reduced to 318.96 μmo/L and 360.71 μmo/L, respectively, which suggested that the substrate affinity of laccase was improved after mutation. The k_cat values of F282L/F306L and Q275P for the substrate ABTS were 574.00 s^-1 and 898.03 s^-1, respectively, which were 1.1 times and 1.7 times that of the wild-type laccase, indicating the improved catalytic efficiency. Q275P demonstrated better performance than the wild-type laccase in pulping, as manifested by the reduction of 0.82 in the Kappa number and the increases of 2.00% ISO, 7.8%, and 7.2% in whiteness, tensile index, and breaking length, respectively. This work lays a foundation for improving the adaptation of laccase to the environment of the papermaking industry.
Laccase/chemistry* ; Directed Molecular Evolution ; Enzyme Stability ; Bacillus pumilus/genetics* ; Mutation ; Biocatalysis ; Catalysis

OBJECTIVES: To compare the clinical effect on Bell's facial palsy in the acute stage between the staging comprehensive treatment with acupuncture-moxibustion and western medication. METHODS: Sixty patients with Bell's facial palsy in the acute stage were randomly divided into an observation group and a control group, with 30 cases in each one. The patients in the control group were administered orally with prednisone acetate tablets and methylcobalamin tablets until the 28th day of illness. In the observation group, the staging comprehensive treatment with acupuncture-moxibustion was adopted. On the affected side, Qianzheng (EX-HN 16), Yifeng (TE 17), Sibai (ST 2), Yangbai (GB 14), Jiache (ST 6), Dicang (ST 4) and Touwei (ST 8), etc. were stimulated. In the acute stage (Day 1 to 7 of illness), the routine acupuncture and the point-toward-point needle insertion were delivered, no any manipulation was exerted at acupoints, and the needles were retained for 30 min. In the subacute stage (Day 8 to 14 of illness), on the base of the treatment as the acute stage, the depth of needle insertion was adjusted at a part of acupoints and the even needling technique was operated by twisting needle. Besides, electroacupuncture (EA) was attached to Qianzheng (EX-HN 16) and Dicang (ST 4), with continuous wave of low intensity and high frequency, 100 Hz, for 20 min. In the recovery stage (Day 15 to 28 of illness), on the base of the treatment as the subacute stage, the heavy stimulation of acupuncture was given, in which, the sticking and lifting needle techniques were delivered after the needles were inserted from Sibai (ST 2) toward Dicang (ST 4), and from Dicang (ST 4) toward Jiache (ST 6), separately; warm needling was operated at Yifeng (TE 17), and EA changed to stimulate the acupoints with the intermittent wave of high intensity and low frequency, 2 Hz, for 30 min. Acupuncture-moxibustion was given once every other day until the end of the 28th day of illness. The level of House-Brackmann facial nerve function rating scale (H-B grade),the score of Sunnybrook facial nerve grading system (Sunnybrook), the score of facial disability index (FDI), the temperature difference in the infrared thermal imaging facial area and electromyogram (EMG) situation of the affected muscle group were observed before and after treatment in the two groups. Using musculoskeletal ultrasound,the facial nerve diameter was detected and the clinical effect was compared between the two groups. RESULTS: After treatment, the level of H-B grade, Sunnybrook score, the scores of physical function and social life function in FDI were improved when compared with those before treatment in the patients of either group (P<0.01, P<0.05), and the results of these evaluations in the observation group were better than those of the control group (P<0.05). After treatment, the temperature difference of the frontal area, the eye area, the zygomatic area and the mouth corner was declined in comparison with that before treatment in the two groups (P<0.05), and the temperature difference in each area in the observation group was lower than that of the control group (P<0.05).The root mean square (RMS) of the frontal muscle group, the zygomatic muscle group and the orbicularis muscle group on the affected side increased in comparison with that before treatment in the two groups (P<0.01), and RMS of the observation group was higher than that of the control group (P<0.05) after treatment. Before treatment, the diameter of the facial nerve on the affected side was larger than that on the healthy side (P<0.01), and after treatment, the diameter on the affected side was reduced when compared with that before treatment in the two groups (P<0.01); the diameter of the facial nerve on the affected side in the observation group was smaller than that of the control group (P<0.05), while, the diameter on the affected side was larger when compared with the healthy side in the control group (P<0.05). The total effective rate of the observation group was 93.3% (28/30), higher than that of the control group (83.3% [25/30], P<0.05). CONCLUSIONS The staging comprehensive treatment with acupuncture-moxibustion is clearly effective on Bell's facial palsy in the acute stage, which affirms the effectiveness of acupuncture-moxibustion for the acute stage of Bell's facial palsy in comparison with conventional western medication.
Humans ; Facial Paralysis/therapy* ; Moxibustion ; Acupuncture Therapy ; Bell Palsy/therapy* ; Face

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective:To analyze the research status of scleral lenses by bibliometric method based on the relevant collection of scleral lenses in the Web of Science database.Methods:Using the scleral lens-related literature collected in the Web of Science Core Collection database in the past 10 years (January 2013 to December 2022) as the object of analysis, bibliometric method and CiteSpace tools were used to conduct visual analysis of the literature.A comprehensive analysis of the volume of literature published, the distribution of countries and institutions, the information of core authors, the distribution of journals, and keyword clustering was performed.Results:A total of 340 articles were retrieved, which were published in 54 journals, with an average of 6.3 articles per journal, involving 301 authors.Research in this area covered 35 countries or regions, and 256 research institutions were involved.Discipline development was mainly in the United States, India, Spain and Australia.The main focus was on scleral lens (scleral contact lens), ocular surface disease, corneal edema, miniature scleral lens, etc.In the past 10 years, the trend of research hot topics in scleral lenses had shifted from the initial study of combining scleral contact lenses with ocular surface diseases to the subsequent study of prosthetic replacement of the ocular surface ecosystem, and the exploration of corneal clearance and shape.From 2013 to 2021, the main focuses were ocular surface diseases, scleral contact lenses, and corneal edema.After 2021, research on ocular surface diseases and keratoplasty declined.From January 2013 to December 2022, emergent keywords related to scleral lens mainly included scleral contact lens, transplantation, anti-host disease, prosthetic device in the first stage, artificial replacement of ocular surface ecosystem and irregular cornea in the second stage, and the research on corneal gap and characteristic shape in the third stage.Optical coherence tomography and corneal topography were commonly used examinations for scleral lens research and fitting.Conclusions:At present, the scleral lens is mainly used for dry eye, corneal diseases, corneal ectasia, keratitis, and corneal transplantation, especially after penetrating keratoplasty and refractive errors.Prosthetic replacement of the ocular surface ecosystem, and the exploration of corneal clearance and shape are the research hotspots in scleral lenses.

Radix Bupleuri has been used in traditional Chinese medicine for over 2000 years with functions of relieving exterior syndrome,clearing heat,regulating liver-qi,and lifting yang-qi.Its medicinal properties have been widely used in Eurasia and North Africa.As the main bioactive compounds in Radix Bupleuri,saikosaponins(especially saikosaponin A and saikosaponin D)have anti-inflammatory,anti-tumor,antioxidant,antivirus,immune regulatory,and liver protective effects.This article reviews the pharmacological activity,mechanism of action,and current applica-tion status of saikosaponins,in order to provide new insights for further research and development of Radix Bupleuri.