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.

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.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

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 implement evidence-based practice for eye management in ICU patients undergoing prone position ventilation and evaluate the effectiveness of applying the best evidence for eye management in this setting.Methods:Through literature retrieval, screening, and evaluation, the best evidence for eye management in ICU patients undergoing prone position ventilation was summarized and compiled into evidence review indicators. From March to June 2024, convenience sampling was used to select 29 ICU prone position ventilation patients and 30 ICU nurses at Shanghai Changzheng Hospital for baseline review to identify obstacles in clinical practice of evidence and develop action strategies based on these obstacles. From July to October 2024, 29 ICU prone position ventilation patients and 29 ICU nurses were selected for evidence-based practice to compare the implementation rates of review indicators before and after evidence-based practice, ICU nurses' knowledge, attitude and practice regarding eye management for prone position ventilation patients, as well as the intraocular pressure during prone position ventilation and the incidence of eye complications within the first week of ICU admission.Results:After evidence-based practice, the implementation rates of all 16 review indicators by ICU nurses were higher than those before evidence-based practice, and the differences were statistically significant ( P<0.05). The total score, knowledge dimension score, and practice dimension score on the Knowledge, Attitude and Practice Questionnaire on Eye Management during Prone Position Ventilation for ICU nurses were higher than those before evidence-based practice, with statistically significant differences ( P<0.05). After evidence-based practice, the intraocular pressure of ICU patients in prone position ventilation for 8 hours and at the end improved, and the differences were statistically significant ( P<0.05). The overall incidence of eye complications within one week of ICU admission decreased from 27.6% to 6.9%, with a statistically significant difference ( P<0.05) . Conclusions:Implementing evidence-based practices for eye management in ICU patients undergoing prone position ventilation can effectively increase nurses' implementation rates of review indicators, enhance their knowledge, attitude, and practice regarding eye management, and reduce the incidence of eye complications in patients.

Background::The increasing incidence of inflammatory bowel disease (IBD) presents significant medical and societal challenges. A well-designed IBD database is crucial for both epidemiological studies and clinical management. However, inconsistencies between regional databases hinder cross-institutional and international research, especially between Eastern and Western societies.Methods::We developed a new IBD database, the 301 IBD database, integrating the IBD clinical characteristics from the Penn IBD database (USA) and the latest IBD guidelines and consensus and clinical practices of the Chinese PLA General Hospital (PLAGH). We applied this database to analyze clinical data of IBD inpatients at PLAGH from 2008 to 2023.Results::The 301 IBD database contains 490 items in 6 sections including demographic characteristics, personal history, clinical phenotype, disease activity, laboratory tests and examinations, and treatment. Features of the 301 IBD database include inpatient focus, biochemical indicators and opportunistic infection focus, and more about ulcerative colitis (UC)-associated complications. Single-center analysis revealed an increasing hospitalization trend, from 2.35% in 2008 to 3.94% in 2023. We found that the clinical characteristics of our UC inpatients are predominantly male (62.5%), extensive lesions (55.1%), low usage of biologics (4.1%), and a high incidence of UC-CRC (3.0%). The clinical characteristics of CD inpatients included male predominance (68.39%), early onset age (35.43 ± 14.75-year-old), and high rate of surgery (25.81%).Conclusion::The 301 IBD database, integrating Eastern and Western clinical data, provides a valuable tool for IBD clinical research. Future international, multicenter collaborations are expected to further enhance its utility.

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.

Objective:To discuss the prevalence of contraindications to progestogens in patients with endometriosis and adenomyosis.Methods:Women of childbearing age aged 15-49 years, except for menopausal and malignant tumors, were enrolled in Peking University First Hospital from April to August 2024 for laparoscopic or open surgery, regardless of whether they had used or would be using progestogen drugs. The patients were divided into two groups: the case group was patients with pathologically confirmed endometriosis and adenomyosis, and the control group was patients with other benign gynecological diseases. The patient′s medical history and clinical data were collected.Results:A total of 745 patients were enrolled, including 362 cases (48.6%, 362/745) in the case group, 383 cases (51.4%, 383/745) in the control group; 61 patients with contraindications to progestogens, including 32 cases (8.8%, 32/362) in the case group, and 29 cases (7.6%, 29/383) in the control group ( χ2=0.398, P>0.05). Among them, there were 33 cases of liver disease, all of which were liver tumor (hepatic hemangioma only), including 18 cases (5.0%, 18/362) in the case group and 15 cases (3.9%, 15/383) in the control group. There were 11 cases of sex hormone-dependent or related tumors (breast cancer only), including 4 cases (1.1%, 4/362) in the case group and 7 cases (1.8%, 7/383) in the control group. There were 10 cases of vascular disease, including 4 cases of diabetic vascular disease, including 2 cases (0.6%, 2/362) in the case group and 2 cases (0.5%, 2/383) in the control group. There were 3 cases of venous thrombosis, including 2 cases (0.6%, 2/362) in the case group and 1 case (0.3%, 1/383) in the control group. There were 3 cases of cardiovascular and cerebrovascular diseases, including 1 case in the case group (0.3%, 1/362) and 2 cases (0.5%, 2/383) in the control group. There were 7 cases of renal insufficiency, including 3 cases of chronic nephritis complicated with renal insufficiency [including 2 cases (0.6%, 2/362) in the case group and 1 case (0.3%, 1/383) in the control group]; two cases of membranous nephropathy complicated with renal insufficiency were in the case group (0.6%, 2/362); one case of diabetic nephropathy complicated with renal insufficiency was in the control group (0.3%, 1/383); one case of uremia was in the case group (0.3%, 1/362). There were no statistically significant differences between the two groups (all P>0.05). Conclusions:There is no difference in the contraindications of progestogens in patients with endometriosis and adenomyosis compared with patients with other gynecological benign diseases. Liver tumors are more common in both two groups.

Objective To develop a carriage-type field operating unit with advantages in mobility and rapid deployment to solve the problems of the traditional field operating equipment in flexibility and environmental adaptability.Methods The carriage-type field operating unit was made based on a BEIBEN TRUCK transport vehicle platform with external and internal modifications.The external modification involved a hydraulic loading platform with a capacity of 2 t and electric lifting function at the rear of the carriage and an external equipment compartment at the bottom.The internal modification included area renovation,tarp modification,facility remodeling and equipment configuration.Results The carriage-type field operating unit behaved better than the traditional field operating vehicle and operating shelter in deployment time,infection control,mobility,temperature control,etc.Conclusion The carriage-type field operating unit gains advantages in mobility,rapid deployment and complete supporting facilities,and can be used as a relatively independent field surgical unit.[Chinese Medical Equipment Journal,2025,46(8):113-117]

Subunit 5B of constitutively photomorphogenic 9 signalosome(CSN5B)is an inhibitory factor for the biosynthesis of vitamin C in the L-galactose synthesis pathway in plants.To create mutants with richer vitamin C in tomato fruits,a dual-target vector of pKSE402-SlCSN5Bwas constructed and trans-formed into the breeding parent of 1912.Based on the molecular biological assay and DNA sequencing,17 transgenic positive lines were determined,and 6 lines of them were genetically mutated at the target site of SlCSN5B,with an editing efficiency of 35.3％.Among the mutants,2 lines were homozygous mu-tants,csn5b-6 with 180 bp deletion and csn5b-8 with 3 bp deletion.The biological traits of two types of deficiency homozygotes without exogenous T-DNA insertion derived from the T1 generation were observed,and there were no significant differences in phenotypes of the plant and fruit.Through physiological tes-ting of red-ripe fruits from T,generation lines of csn5b-6,the GMPase activity and the vitamin C content significantly increased by 43％and 37.8％,respectively,the content of hydrogen peroxide significantly decreased by 25.9％,and the content of soluble solids did not obviously change,compared with the wild type.There were no significant differences in plant traits and physiological characteristics between T1 gen-eration lines of csn5b-8 and the wild type.Based on gene expression analysis and protein structure predic-tion,the results showed that the gene of SlCSN5B normally transcribed,and the loss of large peptide seg-ments of CSN5B encoded by SlCSN5B caused changes in its structure to affect functioning,which led to an increase of vitamin C content in the line of csn5b-6-1 1.The findings suggest that the vitamin C content of tomato fruit can be improved by CRISPR/Cas9-mediated SlCSN5B gene editing,which provides the valuable resources for high-quality breeding in tomato.