Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

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

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*

Objective To investigate the clinical characteristics of intestinal obstruction caused by Meckel diverticulum in children,so as to improve the understanding,diagnosis and treatment of this disease.Methods The clinical data of 103 children with intestinal obstruction caused by Meckel diverticulum admitted to Department of General Surgery,Wuhan Children's Hospital,Tongji Medical College,Huazhong University of Science and Technology from Jul.2015 to Jun.2022 were retrospectively analyzed.There were 78 males and 25 females,with an average age of(4.7±2.6)years old(ranged from 4 months to 12 years old).All 103 cases were admitted for abdominal pain,crying,vomiting or abdominal distension with unknown causes.Results Seventy-four children underwent exploratory laparotomy and 29 underwent laparoscopic exploration.During the operation,it was found that Meckel diverticulum combined with the formation of cord oppressed the intestinal tract,resulting in intestinal obstruction in 65 cases;diverticulum perforation and adhesion obstruction in 15 cases;and secondary intussusception leading to obstruction in 23 cases.Twenty-three cases of secondary intussusception underwent manual reduction of intussusception and Meckel diverticulectomy.Thirty-nine cases were complicated with intestinal necrosis,of which 38 cases underwent cord release,necrotic bowel resection,and intestinal anastomosis;1 case underwent necrotic bowel resection and intestinal fistula due to septic shock.Twelve cases underwent cord release and diverticulectomy,14 cases underwent laparoscopic cord release and diverticulectomy,and 15 cases underwent laparoscopic surgery conversion to diverticulectomy.All patients were clinically cured and followed up for more than 1 year,and no anastomotic leakage,wound infection or other complications occurred.Conclusion The formation of cord is the main cause of intestinal obstruction caused by Meckel diverticulum,with atypical early symptoms,lack of specific symptoms,signs and examination methods,leading to a high misdiagnosis rate.It often causes serious complications such as intestinal necrosis and septic shock.For cases of intestinal obstruction with unknown causes,we should be alert to the possibility of intestinal obstruction caused by Meckel diverticulum.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

OBJECTIVE: To evaluate the partial biomechanical properties of the posterior occipital muscles (rectus capitis posterior major, rectus capitis posterior minor, and obliquus capitis inferior) in patients with cervical vertigo. METHODS: A total of 30 patients with cervical vertigo admitted from April 2024 to September 2024 were included in the vertigo group, and 30 age-and gender-matched healthy subjects were recruited as the normal group. In the vertigo group, there were 21 females and 9 males, with an average age of (24.00±2.25) years;in the normal group, there were 22 females and 8 males, with an average age of (23.00±3.00) years. Shear wave elastography was used to measure the thickness and stiffness of the posterior occipital muscles in both groups. RESULTS: In the vertigo group, there were no statistically significant differences in the Young's modulus values (E) of stiffness of the posterior occipital muscles (rectus capitis posterior major, rectus capitis posterior minor, obliquus capitis inferior) between the left and right sides(P>0.05). The Young's modulus values(E) of stiffness of the right posterior occipital muscles (rectus capitis posterior major, rectus capitis posterior minor, obliquus capitis inferior) in the cervical vertigo group were (39.66±8.21) kPa, (45.61±5.85) kPa, and (43.73±5.22) kPa, respectively, which were significantly higher than those in the normal group 33.97(17.76) kPa, 41.38(8.99) kPa, 38.27(12.58) kPa, with statistically significant differences (P<0.05). In the vertigo group, the Young's modulus values(E) of stiffness of the left rectus capitis posterior major and left obliquus capitis inferior were (40.41±9.13) kPa and (42.11±6.20) kPa, respectively, which were significantly greater than those in the normal group (33.30±11.31) kPa, 38.94(14.62) kPa, with statistically significant differences(P<0.05);however, there was no statistically significant difference in the left rectus capitis posterior minor between the two groups(P>0.05). In the vertigo group, there were no statistically significant differences in the stiffness of the posterior occipital muscles (rectus capitis posterior major, rectus capitis posterior minor, obliquus capitis inferior) between the left and right sides(P>0.05). Additionally, there were no statistically significant differences in the thickness of the bilateral posterior occipital muscles between the vertigo group and the normal group (P>0.05). CONCLUSION The posterior occipital muscles of patients with cervical vertigo are stiffer than those of healthy individuals, while there is no significant difference in muscle thickness between the two groups.
Humans ; Female ; Male ; Elasticity Imaging Techniques/methods* ; Adult ; Vertigo/physiopathology* ; Neck Muscles/physiopathology* ; Young Adult

Objective To explore the pharmacokinetic(PK)characteristics of desloratadine tablets and reference drugs in healthy subjects,and evaluate their bioequivalence and safety.Methods The random,open,two-period,cross-over pharmacokinetic study method was adopted,each subject received a single oral dose of desloratadine tablets test drug(T)or reference drug(R)for 5 mg.The concentrations of desloratadine and 3-hydroxy desloratadine in plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS);and the PK parameters were calculated by WinNonlin 8.1 software to evaluate the bioequivalence.Results The main PK parameters of T and R of desloratadine were as follows:the fasting condition Cmax were respectively(3 809.82±1 016.54)and(3 642.36±777.07)pg·mL-1;AUC0-120h were respectively(5.75 ×104±5.03 ×104)and(5.51 × 104±4.00 × 104)pg·h·mL-1;AUC0-∞ were respectively(6.85× 104±1.03× 104)and(6.37 × 104±7.92 × 104)pg·h·mL-1.The fed condition Cmax were respectively(4 398.98±1 191.22)and(4 744.4±1 511.97)pg·mL-1;AUC0-120h were respectively(5.25 × 104±1.82 × 104)and(5.55 × 104±1.98 × 104)pg·h·mL-1;AUC0-∞ were respectively(5.37 × 104±1.86 × 104)and(5.68 × 104±2.04 × 104)pg·h·mL-1.The 90％confidence interval of Cmax,AUC0-t and AUC0-∞ of desloratadine were all within 80.00％～125.00％.Conclusion There was no significant difference in the main PK parameters between T tablets and R under fasting or high-fat postprandial conditions,and desloratadine tablets were bioequivalent,safe and well tolerated.

Objective:To analysis the safety and feasibility of laparoscopic total hysterectomy in patients with obliterated rectouterine pouch.Methods:A retrospective analysis was conducted on 197 patients who underwent laparoscopic total hysterectomy at Peking University First Hospital, from July 2022 to July 2024. According to intraoperative observations, 197 patients were categorized into two groups: 58 cases with completely obliterated rectouterine pouch (obliterated group) and 139 cases with non-obliterated pouch (control group). General clinical characteristics, perioperative outcomes and 3-month follow-up after surgery were compared between two groups.Results:(1) Baseline characteristics: the age of the obliterated group was (45.7±3.7) years, and the control group was (48.0±3.8) years ( P<0.001). Primary complaint: dysmenorrhea prevalence was 53.4% (31/58) in the obliterated group, and was 35.3% (49/139; P<0.05) in the control group. Surgical indications: the proportion of adenomyosis and ovarian endometrioma was 77.6% (45/58) in the obliterated group, and was 51.1% (71/139; P<0.001) in the control group. No significant differences in body mass index, pelvic surgical history, or preoperative medication between the two groups (all P>0.05). (2) Intraoperative outcomes: the obliterated group demonstrated significantly higher rates of surgical interventions compared to the control group. Superficial endometriosis resection was performed in 91.4% (53/58) of the obliterated group versus 33.8% (47/139) in the control group ( P<0.001). Deep infiltrating endometriosis excision was required in 82.8% (48/58) of the obliterated group, contrasting sharply with 10.1% (14/139) in the control group ( P<0.001). Ureterolysis procedures were similarly elevated in the obliterated group (77.6%, 45/58) compared to the control group (7.9%, 11/139; P<0.001). Operative metrics revealed substantial intergroup disparities: the obliterated group exhibited a median surgical duration of 149.0 minutes (interquartile range: 114.0, 180.0 minutes), significantly prolonged relative to the control group′s 91.0 minutes (77.0, 107.0 minutes; P<0.001). Estimated blood loss followed a parallel pattern, with median volumes of 50.0 ml (20.0, 100.0 ml) in the obliterated group versus 20.0 ml (10.0, 20.0 ml) in the control group ( P<0.001). (3) Postoperative outcomes: the uterine weight of the obliterated group was 200.0 g (132.5, 260.0 g), and the control group was 240.0 g (180.0, 336.0 g; P<0.05). Hospital stay was prolonged in the obliterated group compared with the control group [7.0 days (6.0, 8.3 days) vs 6.0 days (5.0, 7.0 days); P<0.001]. The incidences of postoperative fever in the obliterated group and the control group were 20.7% (12/58) vs 12.2% (17/139; P>0.05). The incidences of minor complications in the obliterated group and the control group were 3.4% (2/58) vs 0 (0/139; P>0.05). No major complications (intraoperative hemorrhage, transfusion, visceral injury, conversion to laparotomy, or thromboembolism) occurred. (4) Follow up at 3 months after surgery: three months postoperatively, all patients underwent outpatient follow-up visits, during which symptoms such as pain were alleviated. Gynecological ultrasound and pelvic examinations were performed, and the vaginal stump exhibited good healing. Conclusion:Laparoscopic total hysterectomy performed by experienced minimally invasive gynecological specialists is safe and feasible for patients with obliterated rectouterine pouch.