BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Objective: To investigate the efficacy and safety of intelligent temperature-pressure-controlled flexible ureteroscopy combined with negative-pressure suction sheath lithotripsy in the treatment of upper urinary tract stones ≤2.5 cm. Methods: The clinical data of 225 patients with ≤2.5 cm upper urinary tract stones treated with this surgical method in our department during Aug. 2023 and Jul. 2024 were retrospectively analyzed. The patients were divided into the dual-control group (n=36) and conventional group (n=189) according to whether or not the intelligent temperature and pressure control device was used during operation. In the dual-control group，the intraoperative temperature and pressure in the renal pelvis were monitored and controlled in real time by the temperature and pressure sensors distributed at the end of the ureteral soft lens. The perioperative parameters，stone-removal rate，complication rate and renal function were compared between the two groups. Results: All operations were successfully completed in both groups. The postoperative procalcitonin (PCT) level [(22.75±5.85) ng/L vs. (29.08±6.60) ng/L，P=0.001]，difference in the white blood cell (WBC) level [(0.24±2.12)×10 cells/L vs. (1.19±2.17)×10 cells/L，P=0.016]，incidence of fever (2.8% vs. 16.9%，P=0.028) and overall complication rate (5.6% vs. 19.6%，P=0.042) were significantly lower in the dual-control group than in the conventional group，while the stone-clearance rate was slightly higher (88.9% vs. 82.5%，P=0.346)，with no significant difference. Conclusion: For upper urinary tract stones ≤2.5 cm，intelligent temperature-pressure-controlled ureteroscopy combined with negative-pressure suction sheath lithotripsy has a satisfactory stone-removal rate and a low rate of complications，which is worthy of clinical promotion.

BACKGROUND: The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism. METHODS: Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured. RESULTS: DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R. CONCLUSION DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals ; MicroRNAs/metabolism* ; Pyroptosis/genetics* ; Mesenchymal Stem Cells/metabolism* ; Myocytes, Cardiac/cytology* ; Mice ; Male ; Mice, Inbred C57BL ; Dental Pulp/cytology* ; Myocardial Reperfusion Injury/therapy* ; MAP Kinase Signaling System/physiology*

OBJECTIVE: To investigate the effectiveness of endoscopic-assisted median nerve decompression with one-stage extensor indicis proprius (EIP) tendon transfer for reconstruction of thumb abduction in patients with severe carpal tunnel syndrome (CTS). METHODS: The clinical data of 12 patients with severe CTS who met the selection criteria between December 2019 and December 2024 were retrospectively analyzed. There were 2 males and 10 females with an average age of 55.4 years ranging from 35 to 67 years. The symptom duration of CTS was 12-120 months (mean, 48.7 months) and the thenar muscle atrophy duration was 6-48 months (mean, 13.4 months). The median nerve was released with the help of endoscope, and the EIP tendon was transferred to reconstruct the abduction function of the thumb. The operation time and complications were recorded. Two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, and pinch force of the thumb were measured and compared before operation and at last follow-up, and the effectiveness was evaluated by Kapandji score and Disabilities of the Arm, Shoulder and Hand (DASH) score. The satisfaction of the operation was evaluated at last follow-up. RESULTS: All surgeries were successfully completed with a mean operation time of 54 minutes (range, 45-68 minutes). All patients were followed up 6-50 months, with an average of 15.3 months. There was no complications such as wound infection, scar pain of wrist, or tendon rupture of transposition, and there were 3 cases of mild limitation of finger extension in the donor site of index finger. At last follow-up, two-point discrimination, palmar abduction angle of the thumb, radial abduction angle of the thumb, Kapandji score, and DASH score were significantly better than those before operation ( P<0.05), but there was no significant difference in thumb pinch force between pre- and post-operation ( P>0.05). The evaluation of surgical satisfaction showed that 7 cases were very satisfied and 5 cases were satisfied. CONCLUSION The combination of endoscopic-assisted median nerve decompression and one-stage EIP tendon transfer effectively improves hand function and quality of life in patients with severe CTS by restoring thumb abduction and alleviating neurological symptoms.
Humans ; Tendon Transfer/methods* ; Male ; Middle Aged ; Carpal Tunnel Syndrome/physiopathology* ; Female ; Decompression, Surgical/methods* ; Aged ; Adult ; Thumb/physiopathology* ; Endoscopy/methods* ; Retrospective Studies ; Median Nerve/surgery* ; Treatment Outcome ; Plastic Surgery Procedures/methods*

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

ObjectiveTo comprehensively elucidate the potential mechanisms of Xiao Xumingtang （XXMT） combined with electroacupuncture （EA） collaboratively in alleviating cerebral ischemia/reperfusion （I/R） injury. MethodThe rat model of cerebral I/R injury was established using the modified suture-occluded method. Seven days after modeling， rats in the XXMT+EA groups were administered XXMT at low （15 g·kg^-1）， medium （30 g·kg^-1）， and high （60 g·kg^-1） doses， alongside daily 20-min EA treatment （stimulating acupoints GV14 and GV20）. Cerebral infarction and neuronal damage were evaluated using the Zea Longa test score， TTC staining， and TUNEL staining. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of NOD-like receptor hot protein domain related protein 3 （NLRP3）， Gasdermin D （GSDMD）， cysteinyl aspartate specific proteinase-1 （Caspase-1）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） in the ischemic area of the cerebral cortex. ResultCompared with the sham group， the I/R group showed a significant increase in neurological deficit scores and infarct volume （P<0.01）， along with a higher apoptosis rate of cortical neurons and elevated mRNA and protein expression levels of NLRP3， GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05）. In contrast， the medium- and high-dose XXMT combined with EA treatment significantly reduced neurological deficit scores and infarct volume （P<0.01）， and decreased the apoptosis rate of cortical neurons as well as the mRNA and protein expression levels of NLRP3， GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05）. The improvement showed a dose-dependent relationship with XXMT. ConclusionThe combined use of XXMT and EA can exert neuroprotective effects by modulating the NLRP3/GSDMD/Caspase-1 signaling pathway， thereby reducing neurological deficits， minimizing brain infarct size， and improving cortical neuronal damage.

Objective To analyze the perioperative outcomes of cardiac valve surgery in patients with asymptomatic SARS-CoV-2 infection. Methods The perioperative clinical data of patients receiving heart valve replacement in the Department of Cardiovascular Surgery, the First Affiliated Hospital of University of Science and Technology of China from November 2022 to February 2023 were retrospectively analyzed. According to whether the patients were infected with SARS-CoV-2, they were divided into a non-infected group and an asymptomatic group. The perioperative data of the patients were compared between the two groups, and the effect of asymptomatic infection on the result of heart valve replacement surgery was analyzed. Results A total of 66 patients were enrolled including 36 males and 30 females with a mean age of 58.0±11.1 years. There were 51 patients in the non-infected group and 15 patients in the asymtomatic group. There were 2 patients of mitral valve replacement, 20 patients of aortic valve replacement, 1 patient of double valve replacement, 3 patients of aortic valve replacement with tricuspid valvoplasty, 22 patients of mitral valve replacement and tricuspid valvoplasty, 18 patients of double valve replacement and tricuspid valvoplasty. Asymptomatic infected patients received more emergency surgery than uninfected patients (26.7% vs. 0.0%, P<0.01). There was no statistical difference in the duration of extracorporeal circulation, aortic occlusion, mechanical ventilation time after the surgery, ICU stay, postoperative drainage volume, or postoperative complications between the two groups. Conclusion Perioperative results of cardiac valve surgery in patients with asymptomatic SARS-CoV-2 infection and non-infection are almost the same.

Objective To compare the efficacy of mediastinoscope-assisted transhiatal esophagectomy (MATHE) and functional minimally invasive esophagectomy (FMIE) for esophageal cancer. Methods Patients who underwent minimally invasive esophagectomy at Jining No.1 Hospital from March 2018 to September 2022 were retrospectively included. The patients were divided into a MATHE group and a FMIE group according to the procedures. The patients were matched via propensity score matching (PSM) with a ratio of 1 : 1 and a caliper value of 0.2. The clinical data of the patients were compared after the matching. Results A total of 73 patients were include in the study, including 54 males and 19 females, with an average age of (65.12±7.87) years. There were 37 patients in the MATHE group and 36 patients in the FMIE group. Thirty pairs were successfully matched. Compared with the FMIE group, MATHE group had shorter operation time (P=0.022), lower postoperative 24 h pain score (P=0.031), and less drainage on postoperative 1-3 days (P<0.001). FMIE group had more lymph node dissection (P<0.001), lower incidence of postoperative hoarseness (P=0.038), lower white blood cell and neutrophil counts on postoperative 1 day (P<0.001). There was no statistically significant difference in the bleeding volume, R0 resection, hospital mortality, postoperative hospital stay, anastomotic leak, chylothorax, or pulmonary infection between the two groups (P>0.05). Conclusion Compared with the FMIE, MATHE has shorter operation time, less postoperative pain and drainage, but removes less lymph nodes, which is deficient in oncology. For some special patients such as those with early cancer or extensive pleural adhesions, MATHE may be a suitable surgical method.

Background Maternal exposure to bisphenol A (BPA) during pregnancy is closely related to adverse growth and development conditions such as preterm birth and low birth weight, but the relevant mechanisms are still unclear. UDP-glucuronosyltransferases (UGTs) can regulate the excretion of BPA conjugating with glucuronic acid through urine, which is one of the important pathways for BPA elimination. Objective To explore the changes in the expression of UGTs in placenta and fetal liver of rats before birth induced by maternal exposure to BPA during pregnancy. Methods Thirty SPF-grade healthy SD pregnant rats were randomly divided into five groups: control group, 0.05, 0.5, 5, and 50 mg·kg⁻¹ BPA groups. The pregnant rats were exposed to BPA dissolved in corn oil via oral gavage daily from gestational day (GD) 5 to GD 19. After anesthesia, the pregnant rats were sacrificed on GD 20 and the placentas were collected. Body length, tail length, and weight of the fetal rats were measured. Fetal liver tissues were then separated, and organ weights were measured. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to determine the mRNA and protein levels of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in the placenta and fetal liver tissues in each group. Results There were no differences in body length and tail length of the pups after maternal exposure to BPA during pregnancy. The fetal body weight and placenta weight in the 5 and 50 mg·kg⁻¹ BPA groups and the liver weight in the 5 mg·kg⁻¹ BPA group reduced compared with the control group (P<0.05). The results of UGTs expressions in placenta showed that compared with the control group, the UGT1A1 mRNA levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) and the UGT1A1 protein level in placenta of the 50 mg·kg⁻¹ BPA group increased (P<0.05); the UGT1A6 mRNA and protein levels in placenta of each BPA group did not change (P>0.05); the UGT1A9 mRNA level in placenta of the 50 mg·kg⁻¹ BPA group and the UGT1A9 protein levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05); while the levels of UGT2B1 mRNA in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). The results of UGTs expressions in fetal liver showed that compared with the control group, the UGT1A1, UGT1A6, UGT1A9, and UGT2B1 mRNA levels of each BPA group increased (P<0.05); no obvious alternation was observed in UGT1A6 protein levels in each BPA group (P>0.05); the relative protein levels of UGT1A9 in fetal liver in the 50 mg·kg⁻¹ BPA group increased (P<0.05); conversely, the relative protein levels of UGT2B1 in fetal liver in the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). Conclusion Maternal exposure to BPA during pregnancy can elevate the UGT1A1 gene and protein expressions, inhibit the UGT1A9 gene and protein expressions and UGT2B1 gene expressions in placenta. Besides, maternal exposure to BPA during pregnancy can raise the gene expressions of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in fetal liver, as well as the protein expression of UGT1A9, but inhibit the protein expression of UGT2B1. These changes may contribute to fetal developmental abnormalities after maternal exposure to BPA during pregnancy.