[Objective] To explore the safety and efficacy of submucosal injection of glycerol and fructose saline in bladder tumor endoscopic submucosal dissection (BT-ESD) with a 450 nm blue laser semiconductor treatment machine in the treatment of non-muscular invasive bladder cancer (NMIBC). [Methods] Clinical data of 20 patients with bladder tumor treated with submucosal injection of glycerol and fructose saline BT-ESD via a 450 nm blue laser semiconductor treatment machine at our hospital during Nov.2023 and Apr.2024 were retrospectively analyzed.The patients included 13 males and 7 females, aged (64.95±6.89) years, tumor diameter (1.02±0.24) cm, and preoperative hemoglobin (Hb) (130.55±4.36) g/L.The operation time, Hb the next day after operation, positive rate of tumor basal biopsy, postoperative bladder irrigation time, catheter indwelling time, postoperative hospital stay, complications and recurrence rate were recorded. [Results] All operations were successful, and 28 lesions were removed.The postoperative pathological results confirmed that all cases were NMIBC, and the basal mucosa biopsies were negative.The operation time was (9.40±3.14) min, postoperative Hb (130.15±4.59) g/L, bladder irrigation time (17.70±1.34) h, catheter indwelling time 1 day, and postoperative hospital stay 1 day.There were no complications such as obturator nerve reflex, bladder perforation.There were no need for blood transfusion, no conversion to open surgery, and no secondary bleeding after operation.No tumor recurrence was found during 6-month postoperative follow up. [Conclusion] Submucosal injection of glycerol and fructose saline BT-ESD with a 450 nm blue laser semiconductor treatment machine is a safe and effective method for the treatment of NMIBC.It has advantages of whole enucleation of bladder tumor, clear basal layer, small amount of bleeding, short operation time and few complications.It can be used as a day surgery and is worthy of clinical promotion.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

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*

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective To investigate the effects of miR-4531/CX3CL1 signaling pathway on the vascular injury in preeclampsia, and to search possible targets for early diagnosis and prevention of preeclampsia. Methods Placental tissue samples were obtained from 10 patients with late-onset preeclampsia and 10 normal pregnant women in the Obstetrics and Gynecology Department of Minhang Hospital, Fudan University from October 2021 to December 2022. The levels of miR-4531 and CX3CL1 were evaluated by qRT-PCR. Cell transfection was performed by lipofectamine 2000 in vitro. The binding relationship between miR-4531 and CX3CL1 was determined by luciferase reporter assay. The apoptosis of neutrophils, the migration, repair, colony formation and cell-free DNA (cfDNA) release of human umbilical vein endothelial cells (HUVECs) were detected. Results MiR-4531 was significantly downregulated, and CX3CL1 was upregulated in placental tissues of preeclampsia patients (P＜0.05). Luciferase report assay confirmed the direct binding relationship between miR-4531 and CX3CL1. Upregulation of miR-4531significantly promoted the migration, proliferation, repair, and inhibited cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). However, downregulation of miR-4531 obviously inhibited the proliferation, migration, repair, and enhanced cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). Conclusions The miR-4531is downregulated in placental tissues of preeclampsia parients and is a potential therapeutic target for preeclampsia. It might cause endothelial damage and an abnormal hypercoagulable state under hypoxic condition by targeting and regulating the CX3CL1 pathway.

Objective To explore the efficacy and safety of"ditching and ridge removal"with 450 nm semiconductor blue laser in the treatment of large volume benign prostatic hyperplasia(BPH),in order to promote the clinical application of this method.Methods A retrospective study was conducted on 30 patients with large volume BPH treated with"ditching and ridge removal"with 450 nm semiconductor blue laser in Yingsheng Branch of Tai'an Central Hospital during Sep.and Dec.2023.The laser operation time,level of hemoglobin before and after operation,bladder irrigation time after operation,urinary catheter indwelling time,postoperative hospital stay,and intraoperative and postoperative complications were recorded.The changes of international prostate symptom score(IPSS),quality of life scale(QoL)score,maximum urinary flow rate(Qmax)and post-void residual volume(PVR)were compared before and 1 month after operation.Results The volume of prostate was(104.5±14.52)mL,the laser operation time was(20.13±2.98)min,and the bladder irrigation time was(20.27±2.56)h.The catheter was removed in all patients 2 days after operation,and all patients were discharged 3 days after operation.One month after operation,the IPSS,QoL,Qmax and PVR were significantly improved as compared with those before operation(P＜0.05).No complications occurred during the follow-up.Conclusion"Ditching and ridge removal"with 450 nm semiconductor blue laser is a new,safe and effective method in the treatment of large volume BPH.

Objective To compare the clinical efficacy and safety of transurethral blue laser vaporization of prostate and transurethral resection of prostate(TURP)in the treatment of benign prostatic hyperplasia(BPH).Methods The clinical data of 142 BPH patients undergoing surgery in our hospital during Jan.and Aug.2023 were retrospectively analyzed.The patients were divided into blue laser group(n=72)and TURP group(n=70).The operation time,hemoglobin(Hb)decrease,bladder irrigation time,catheter indwelling time and postoperative hospital stay were compared between the two groups.The changes of international prostate symptom score(IPSS),quality of life score(QoL),maximum urinary flow rate(Qmax),postvoid residual volume(PVR),international index of erectile function-5(IIEF-5)score and complications before and 6 months after operation were also compared.Results Six months after operation,the IPSS,QoL,Qmax and PVR were significantly improved in both groups(P＜0.05),but there were no significant differences between the two groups(P＞0.05).Compared with the TURP group,the blue laser group had shorter operation time[(47.04±4.03)min vs.(25.46±5.84)min],shorter postoperative bladder irrigation time[(54.17±4.99)h vs.(21.18±4.11)h],shorter catheter indwelling time[5(5,6)d vs.2(2,2)d],shorter postoperative hospital stay[7(7,8)d vs.4(3,4)d],less Hb decrease[(9.61±2.16)g/L vs.(4.31±2.34)g/L],and lower incidence of complications(51.4％vs.4.2％),with significant differences(P＜0.05).Six months after surgery,the blue laser group had higher IIEF-5 score than that the TURP group[(20.06±2.13)vs.(18.93±1.85)],with significant difference(P＜0.05).Conclusion Both transurethral blue laser vaporization of prostate and TURP can effectively treat BPH,but the former is more effective,for it has advantages of short recovery time,few complications and small impact on the sexual function of patients.