Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

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

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

The mitochondrial unfolded protein response(UPRmt)represents a crucial intracellular stress response mechanism that plays a fundamental role in maintaining mitochondrial and cellular homeostasis. Growing evidence suggests that dysregulation of UPRmt contributes significantly to the pathogenesis of various systemic disorders, including neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, as well as age-related pathologies. Emerging research has particularly highlighted the involvement of UPRmt in ocular diseases, including cataracts, glaucoma, and diabetic retinopathy. This comprehensive review examines the physiological functions of UPRmt and its regulatory mechanisms in age-related eye diseases. The roles of key UPRmt downstream effector molecules in ocular cell populations such as lens epithelial cells, retinal pigment epithelial cells, and retinal ganglion cells are systematically analyzed. Importantly, the dual regulatory nature of UPRmt in ocular pathophysiology is discussed, that is, its moderate activation promotes mitochondrial homeostasis, mitigates oxidative stress, and suppresses inflammatory responses, its chronic or excessive activation triggers apoptotic pathways, induces metabolic dysfunction, and ultimately accelerates disease progression. By elucidating these mechanisms, our review provides novel insights into ocular disease pathogenesis and proposes potential therapeutic strategies targeting UPRmt modulation for the prevention and treatment of age-related eye disorders.

Diabetic cataract, a prevalent ocular complication of diabetes mellitus, arises from a complex interplay of pathological mechanisms, with oxidative stress and glycation stress playing central roles. Autophagy, a critical cellular self-protection mechanism, sustains intracellular homeostasis by selectively degrading damaged organelles and misfolded proteins, thereby counteracting the detrimental effects of oxidative and glycation stress under hyperglycemic conditions. Emerging evidence indicates a synergistic interaction between glycation stress and oxidative stress, which may exacerbate autophagic dysfunction and accelerate the onset and progression of diabetic cataract. However, the precise molecular mechanisms underlying this relationship remain incompletely understood. This review systematically examines the regulatory role of autophagy inthe pathogenesis of diabetic cataract, with a particular focus on how autophagic impairment influences disease progression under the combined effects of glycation and oxidative stress. By elucidating these mechanisms, the paper aims to provide novel insights into molecular diagnostic approaches and targeted therapeutic strategies for diabetic cataract.

OBJECTIVE: To observe the clinical effect of Tiaoshen Guben holistic therapy of acupuncture and moxibustion (holistic treatment with acupuncture and moxibustion by adjusting the mind and consolidating the root) on comorbidity of depression and insomnia. METHODS: Twenty-four patients with comorbidity of depression and insomnia were included and treated with Tiaoshen Guben holistic therapy of acupuncture and moxibustion. Acupuncture was applied to Baihui (GV20), Guanyuan (CV4), bilateral Neiguan (PC6), etc. The refined moxibustion therapy was delivered at Zhongwan (CV12), Qihai (CV6), bilateral Yongquan (KI1), etc. Subcutaneous embedding therapy with thumb-tack needle was adopted at bilateral Xinshu (BL15), bilateral Pishu (BL20), etc. The intervention was operated once every other day, 3 treatments a week, and for 6 consecutive weeks. Before and after treatment completion, and in 1 month after treatment, Pittsburgh sleep quality index (PSQI) and Hamilton's depression scale (HAMD-17) were adopted to assess sleep quality and depression symptoms in the patients, respectively. Before and after treatment completion, using functional magnetic resonance imaging (fMRI), the functional connectivity (FC) of locus coeruleus (LC) in brain regions was evaluated; and the levels of serum norepinephrine (NE), cortisol (CORT), adrenocorticotropic hormone (ACTH) and corticotropin releasing hormone (CRH) were detected. RESULTS: Compared with the scores before treatment, PSQI and HAMD-17 scores after treatment completion and in 1 month after treatment were reduced (P<0.01); and strengthened FC was revealed between the right LC and the pars opercularis of the left inferior frontal gyrus, as well as the lateral occipital lobe region. After treatment completion, serum NE was elevated (P<0.01), the levels of CORT, ACTH and CRH were reduced (P<0.01). Before and after treatment completion, the difference in FC between the right LC and the pars opercularis of the left inferior frontal gyrus was negatively correlated with the differences in PSQI score (r = -0.484, P = 0.016) and HAMD-17 score (r = -0.233, P = 0.027). CONCLUSION Tiaoshen Guben holistic therapy of acupuncture and moxibustion can effectively alleviate depression symptoms and improve sleep quality in the patients with comorbidity of depression and insomnia, which is obtained probably through reducing the levels of serum CORT, ACTH and CRH, increasing serum NE, strengthening the FC of the right LC with the pars opercularis of the left inferior frontal gyrus and the lateral occipital lobe region.
Humans ; Moxibustion ; Sleep Initiation and Maintenance Disorders/therapy* ; Male ; Female ; Middle Aged ; Adult ; Acupuncture Therapy ; Depression/complications* ; Aged ; Young Adult ; Acupuncture Points ; Comorbidity

Persistent inflammation plays a pivotal role in the initiation and progression of renal fibrosis. Activation of the pattern recognition receptor retinoic acid-inducible gene-I (RIG-I) is implicated in the initiation of inflammation. This study aimed to investigate the upstream mechanisms that regulates the activation of RIG-I and its downstream signaling pathway. Eight-week-old male C57BL/6 mice were used to establish unilateral ureteral obstruction (UUO)-induced renal fibrosis model, and the renal tissue samples were collected 14 days later for analysis. Transforming growth factor-β (TGF-β)-treated mouse renal tubular epithelial cells were used in in vitro studies. The results demonstrated that, compared to the control group, UUO kidney exhibited significant fibrosis, which was accompanied by the increases of RIG-I, p-NF-κB p65 and inflammatory cytokines, such as TNF-α and IL-1β. Additionally, the protein level of the E3 ubiquitin ligase RNF125 was significantly downregulated and predominantly localized in the renal tubular epithelial cells. Similarly, the treatment of tubular cells with TGF-β induced the increases in RIG-I, p-NF-κB p65 and inflammatory cytokines while decreasing RNF125. Co-immunoprecipitation (Co-IP) assays confirmed that RNF125 was able to interact with RIG-I. Overexpression of RNF125 promoted the ubiquitination of RIG-I, and accelerated its degradation via the ubiquitin-proteasome pathway. Overexpression of RNF125 in UUO kidneys and in vitro tubular cells effectively mitigated the inflammatory response and renal fibrosis. In summary, our results demonstrated that the decrease in RNF125 under pathological conditions led to reduction in RIG-I ubiquitination and degradation, activation of the downstream NF-κB signaling pathway and increase in inflammatory cytokine production, which promoted the progression of renal fibrosis.
Animals ; Fibrosis ; Male ; Ubiquitination ; Mice ; Mice, Inbred C57BL ; DEAD Box Protein 58 ; Ubiquitin-Protein Ligases/physiology* ; Inflammation/metabolism* ; Ureteral Obstruction/complications* ; Kidney/pathology* ; Signal Transduction ; Transforming Growth Factor beta/pharmacology*