BACKGROUND:The content of serum thrombin in patients with osteoarthritis is significantly higher than that in normal individuals,and thrombin can induce inflammatory degeneration of rat chondrocytes,suggesting that inhibiting the function of thrombin may become a method for treating osteoarthritis.Celecoxib is a common therapeutic drug for the clinical treatment of osteoarthritis.It is not yet known whether it improves chondrocyte degeneration by inhibiting the activity of thrombin. OBJECTIVE:To investigate the effect of celecoxib on thrombin-induced degeneration of rat chondrocytes. METHODS:Thrombin levels in the serum of osteoarthritis patients and normal individuals were detected by an ELISA kit.Primary chondrocytes of neonatal Sprague-Dawley rats were isolated,and all experiments were performed with cells from passage one.Chondrocytes were randomly divided into three groups:control group,thrombin group,and celecoxib group.The cell morphology of the three groups was observed under an inverted microscope,and an Edu kit was used to detect the cell proliferation.qRT-PCR was used to detect the expression of extracellular matrix components(aggrecan,elastin,cartilage oligomeric matrix proteins),inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),and chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6).The expression of type 2 collagen α1 was detected by immunofluorescence.Western blot method was used to detect the expression of catabolic metabolism genes,such as matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2. RESULTS AND CONCLUSION:Patients with osteoarthritis had higher levels of thrombin in the serum compared with normal individuals.Under the microscope,celecoxib was found to significantly inhibit fibroid changes in chondrocytes.Compared with the thrombin group,celecoxib inhibited the proliferation of chondrocytes.The downregulation of extracellular matrix gene expression,such as type II collagen α1,in the thrombin group was inhibited by celecoxib(P<0.05).Thrombin promoted the expression of inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6),as well as catabolic genes(matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2),and under the intervention of celecoxib,the expression of these genes could be downregulated(P<0.05).Overall,these findings indicate that celecoxib inhibits the pro-inflammatory effects of thrombin and thereby ameliorates chondrocyte degeneration in rats.

Objective:To investigate the effectiveness and safety of low-dose oral misoprostol solution for cervical ripening in late gestation.Methods:This was a prospective cohort study including 396 primiparas with singleton pregnancy who received low-dose oral misoprostol solution for cervical ripening (oral group) in Peking University Third Hospital from March to October 2022. They were further allocated to receive oral misoprostol alone (OA group, n=167) or oral misoprostol in combination with oxytocin/amniotomy (OC group, n=229). Moreover, 218 cases who received vaginal misoprostol for cervical ripening (vaginal group) during the same period in 2021 were reviewed (a retrospective cohort). Among them, 77 were given vaginal misoprostol alone (VA group) and 141 received vaginal misoprostol in combination with oxytocin/amniotomy (VC group). The OA group and VA group (72 and 73 cases) as well as the OC group and VC group (108 and 103 cases) were matched using propensity scores. Basic clinical information, hospital stay, duration of labor induction, uterine hyperstimulation, rate of labor initiation, vaginal delivery rate, rate of delivery within 24 h, duration of labor, neonatal condition, adverse pregnancy outcomes, and other information were compared between different groups. All data were statistically analyzed using independent sample t test, analysis of variance, nonparametric test, Chi-square test, or Fisher's exact probability test. Logistic regression model was used to analyze the factors affecting the labor initiation and the failure of labor induction. Results:The average hospital stay, the duration from medication to labor initiation and the duration from medication to vaginal delivery were significantly shorter in the oral group than those in the vaginal group [(5.4±2.4) vs. (6.5±2.6) d, (34.2±24.1) vs. (38.9±25.7) h, (45.8±25.8) vs. (53.4±27.8) h; t=5.24, 2.10 and 3.39; all P<0.05]. The total labor initiation rate and vaginal delivery rate in the oral group were significantly higher than those in the vaginal group [92.9% (368/396) vs. 83.5% (182/218), 72.2% (286/396) vs. 60.1% (131/218); χ 2=13.43 and 9.50; both P<0.05]. The incidence of failed induction of labor, uterine hyperstimulation, fetal distress, and intrauterine infection in the oral group were lower than those in the vaginal group [2.0% (8/396) vs. 6.9% (15/218), 4.3% (17/396) vs. 17.9% (39/218), 8.8% (35/396) vs. 14.7% (32/218), 1.3% (5/396) vs. 3.7% (8/218); χ 2=9.21, 31.36, 4.93 and 3.93; all P<0.05]. The duration from medication to labor initiation and to vaginal delivery in the OA group were higher than those in the VA group [(25.8±17.0) vs. (17.4±10.8) h, (37.2±18.8) vs. (29.7±13.5) h; t=3.49 and 2.74; both P<0.05]. There were no significant differences in the labor initiation rate, vaginal delivery rate, rate of delivery within 24 h or the incidence of failed induction of labor between the OA and VA groups (all P>0.05). Women in the VA group were more likely to develop uterine hyperstimulation than those in the OA group [19.2% (14/73) vs. 4.2% (3/72), χ2=7.89, P=0.005]. There were no significant differences in the duration from medication to labor initiation or to vaginal delivery between the VC and OC groups (both P>0.05), but the duration were significantly longer than those in the corresponding medication alone group (VC vs. VA groups: (49.7±24.6) vs. (17.4±10.8) h and (61.6±25.7) vs. (29.7±13.5) h, t=5.31 and 5.13, both P<0.05; OC vs. OA groups: (45.3±26.6) vs. (25.8±17.0) h and (56.1±27.2) vs. (37.2±18.8) h, t=10.35 and 9.78, both P<0.05]. The labor initiation rate, vaginal delivery rate and rate of delivery within 24 h in the OC group were higher than those in the VC group [88.9% (96/108) vs. 77% (87/113), 63.0% (68/108) vs. 47.8% (54/113), 10.3% (7/108) vs. 0.0% (0/113); χ 2=5.49, 5.14 and 7.56; all P<0.05]. The incidence of uterine hyperstimulation in the OC group was 4.6% (5/108), which was lower than that in the VC group [18.6% (21/113), χ 2=10.37, P=0.001]. Logistic regression analysis showed that oral misoprostol and gestational age were positively correlated with labor initiation [ OR (95% CI): 2.18 (1.24-3.90) and 1.43 (1.14-1.79)], while maternal age was negatively correlated with labor initiation [ OR (95% CI): 0.90 (0.82-0.98)]. Moreover, failed induction of labor was negatively correlated with oral misoprostol [ OR (95% CI): 0.37 (0.14-0.91)], but positively correlated with maternal age [ OR (95% CI): 1.21 (1.05-1.40)]. Conclusions:Oral administration of low-dose misoprostol solution is as effective as vaginal misoprostol in promoting cervical ripening. Besides, it can shorten the average hospital stay and reduce the incidence of uterine hyperstimulation, suggesting that low-dose oral misoprostol solution is relatively safer and can be used to promote cervical ripening in late gestation.

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.

Objective:To investigate the clinical efficacy of over-the-top reconstruction combined with the modified Lemaire technique in the treatment of anterior cruciate ligament (ACL) injuries with pivot-shift positive.Methods:From March 2020 to October 2021, a total of 46 patients with ACL injury and pivot-shift test grade II or above were admitted to Xinhua Hospital Affiliated to Dalian University. There were 28 males and 18 females, aged 28.0±10.5 years (range, 15-45 years). All cases were unilateral, including 17 cases of left knee and 29 cases of right knee. The pivot-shift test showed that 30 cases were grade II and 16 cases were grade III, and the cause of injury was sports injury. The semitendinosus muscle and gracilis muscle were harvested, and the ACL was reconstructed with the over-the-top combined modified Lemaire technique. The International Knee Documentation Committee (IKDC) score, Lysholm score and KT-2000 side-to-side difference before and after operation were compared.Results:All patients successfully completed the operation and were followed up for 26.6±2.3 months (range, 24-28 months). The Lysholm scores of the patients at 3 months and 24 months after operation were 73.6±4.3 and 91.6±2.8, which were higher than those before operation (58.5±4.6), and the difference was statistically significant ( F=18.351, P<0.001). The IKDC scores of patients at 3 months and 24 months after operation were 59.0±2.0 and 91.8±3.2, respectively, which were higher than those before operation 50.3±2.8, and the difference was statistically significant ( F=17.290, P<0.001). The side-to-side difference of KT-2000 was 1.7±0.8 mm and 1.5±0.4 mm at 3 and 24 months after operation, respectively, which was lower than that before operation (5.9±1.1 mm), and the difference was statistically significant ( F=14.192, P<0.001). At 24 months after operation, 3 patients had pivot shift test grade I and 4 patients had Lachman test grade I, but they complained of good knee stability and did not receive further treatment. At the last follow-up, there were no complications such as incision and intra-articular infection, deep vein thrombosis, knee stiffness, quadriceps musculus ossificans myositis, and reconstruction ligament rupture. All patients returned to sports with an average time of 15.7±2.6 months (range, 12-24 months). Conclusion:Over-the-top reconstruction combined with the modified Lemaire technique for the treatment of ACL injury with positive pivot shift test effectively improves knee function and promotes the patient's return to sports, with a low incidence of surgical complications.

Objective:To evaluate the short-term clinical outcomes of meniscus reconstruction using autologous peroneus longus tendon grafts.Methods:A retrospective analysis was conducted on 20 patients (12 males, 8 females) with a mean age of 37.8±5.7 years (range, 31-47 years) and a mean body mass index (BMI) of 26.3±5.8 kg/m 2 (range, 20.1-31.3 kg/m 2) who underwent meniscal reconstruction with autologous peroneus longus tendon in Affiliated Xinhua Hospital of Dalian University from June 2020 to June 2022. A control group of 20 patients (15 males, 5 females), with a mean age of 39.1±6.2 years (range, 32-47 years) and a mean BMI of 25.6±5.4 kg/m 2 (range, 20.2-32.7 kg/m 2), underwent partial meniscectomy during the same period. Clinical outcomes were assessed using the International Knee Documentation Committee (IKDC) score, Lysholm score, visual analogue scale (VAS) for pain, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 3, 6, 12, and 24 months postoperatively. The morphology and signal intensity of grafts, Recht grading for cartilage damage, and the need for secondary arthroscopy were also evaluated. Results:The mean follow-up duration was 24.3±4.3 months for the tendon graft group and 24.2±3.6 months for the partial meniscectomy group. At 3 and 6 months postoperatively, the partial meniscectomy group demonstrated superior knee function scores compared to the tendon graft group ( P<0.05). Similarly, VAS were lower in the partial meniscectomy group at 3 months postoperatively ( P<0.05), although no significant difference was found at 6 months ( P>0.05). By 12 months postoperatively, differences in pain and function between the two groups were no longer statistically significant ( P>0.05). At 24 months, the tendon graft group exhibited significantly better outcomes in terms of the Lysholm score (84.31±12.20 vs. 72.67±14.18), IKDC score (82.21±10.55 vs. 74.09±11.68), VAS score (2.10±1.74 vs. 3.80±1.81), and KOOS score (85.37±13.14 vs.75.14±17.94) compared to the partial meniscectomy group ( P<0.05). Regarding graft healing, 19 patients in the tendon graft group demonstrated a grade 3 graft-residual meniscus complex at 24 months, significantly improved from 5 patients at 3 months postoperatively. Furthermore, no grafts showed a grade 3 signal intensity at 3 months, while 19 patients showed such improvements by 24 months. MRI at the 24-month follow-up revealed cartilage damage in 7 patients in the tendon graft group and 20 patients in the partial meniscectomy group, with severe cartilage damage (Recht grade>II) observed in 1 patient in the tendon graft group and 7 patients in the partial meniscectomy group. All 20 patients in the tendon graft group achieved minimal clinically significant differences by 24 months, and 4 of them underwent secondary arthroscopy, which revealed vascularization between the graft and residual meniscal tissue. Conclusion:The use of the peroneus longus tendon for meniscal reconstruction reduces knee pain, enhances knee function, and effectively fills the tibiofemoral joint space while protecting the articular cartilage through graft remodeling.

Objective To investigate the population distribution,biofilm formation and drug resistance of Staphylococcus aureus isolated from pressure ulcers infected patients in the hospital,and to provide important clinical evidence.Methods From May 2019 to May 2022,a total of 126 strains of Staphylococcus aureus relat-ed to pressure ulcer infections were collected in the hospital.The bacteria were identified by Vitek MS mass spectrometer,and the drug susceptibility test was performed by disk diffusion method(K-B method).The drug susceptibility results were analyzed according to the standards of the American Association for Clinical Laboratory Standardization(ACLA),2016-M100.The crystal violet staining method was used to detect the biofilm of Staphylococcus aureus and determine its formation ability.Glucose and silver ion powder were add-ed to the biofilm respectively,and their effects on biofilm formation were observed.Results From May 2019 to May 2022,126 strains of Staphylococcus aureus related to pressure ulcer infection were collected from the hospital.Pressure ulcer was detected at all ages and levels.The proportion of strains forming biofilm was 73.00％,and the proportion of strains forming biofilm was 81.81％in the strain isolated from stage Ⅳ pres-sure ulcer,which was higher than that in the strain isolated from other stages(Ⅱ and Ⅲ)(63.33％),and the differences were statistically significant(P＜0.05).Strains with different biofilm formation ability had higher resistance rates to penicillin G,tetracycline,ciprofloxacin,sulfamethoxazole/trimethoprim,but lower resist-ance rates to teicoplanin and levofloxacin.No Gram-positive bacteria resistant to vancomycin were detected.There were no significant differences in drug resistance of Staphylococcus aureus in different biofilm levels(P＞0.05).11.10 mmol/L glucose could promote the formation of biofilm,10.00 μg/mL silver ion antibacte-rial gel could inhibit the formation of biofilm.Conclusion The biofilm formation ability of Staphylococcus au-reus to cause stage Ⅳ pressure ulcer infection is strong and the formation of biofilm is related to the stage of pressure ulcer.The antimicrobial resistance of Staphylococcus aureus producing membrane has no obvious re-lationship with the grade of biofilm.The use of silver ions and the reduction of blood glucose level have a cer-tain inhibitory effect on biofilm formation.

Objective:To explore the clinical value of antegrade transabdominal nasobiliary duct placement in the treatment of fine diameter choledocholithiasis in the elderly.Methods:From June 2021 to June 2022, 60 elderly patients with fine diameter common bile duct stones who were treatment in the Shandong Chengwu County People′s Hospital were enrolled. All patients underwent laparoscopic common bile duct exploration (LCBDE), 28 patients in the experimental group were underwent antegrade transabdominal placement of nasal bile ducts, 32 patients in the control group were treated with T-tube drainage. The operative index, postoperative complications and total medical expenses, postoperative patient satisfaction were compared between the two groups.Results:The operation was successful in both groups, and no conversion to laparotomy or death occurred. The indwelling time of common bile duct drainage, postoperative hospital stay in the experimental group were shorter than those in the control group, the incidence of postoperative pain was lower than that in the control group, the postoperative patient satisfaction was higher than that in the control group: (6.46 ± 1.04) d vs. (33.63 ± 1.19) d, (8.11 ± 0.74) d vs. (10.38 ± 1.54) d, 3.6%(1/28) vs. 21.9%(7/32), (9.21 ± 0.83) scores vs. (7.56 ± 0.62) scores, there were statistical differences ( P<0.05). The surgical time, postoperative activity time, gastrointestinal function recovery time and total medical expenses between the two groups had no statistical differences( P>0.05). The postoperative complications between the two groups had no statistical differences ( P>0.05). Conclusions:Anterior transabdominal nasobiliary duct placement can shorten the retention time and hospitalization time of the common bile duct drainage tube, reduce the incidence of postoperative complications, and promote rapid recovery. It is a safe and effective surgical method.

Geobacillus thermoglucosidasius is a kind of Gram-positive facultative anaerobic bacteria. The fast growth rate under high temperature and less susceptibility to microbial contamination enable G. thermoglucosidasius to be a desirable producer of biofuels and high-value-added chemicals for the next-generation industrial biotechnology. However, compared with the classical model strain Escherichia coli, the applications of G. thermoglucosidasius are hampered by its low transformation efficiency. This study aimed at obtaining competent cells with high transformation efficiency through inactivating restriction enzymes, adding cell membrane inhibitors and cell wall weakening agents. The results showed that the electro-transformation efficiency achieved 1.2×10⁴ CFU/(μg DNA) by knocking out four genes encoding restriction enzymes. Adding a certain amount of tween 80, dl-threonine and glycine further increased the competent efficiency about 22.5, 44, and 334 times, respectively. The electro-transformation efficiency was enhanced to 4.6×10⁶ CFU/(μg DNA) under the optimized conditions, laying a foundation for genetic manipulation and metabolic engineering of G. thermoglucosidasius.
Electroporation ; Electroporation Therapies ; Bacillaceae ; Cell Membrane ; Escherichia coli/genetics*

Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.
Mice ; Animals ; Microcephaly/genetics* ; Autistic Disorder/metabolism* ; Autism Spectrum Disorder/metabolism* ; Nerve Tissue Proteins/metabolism* ; Brain/metabolism* ; Mice, Knockout ; Cell Cycle Proteins/metabolism*

{L-End}Objective To analyze the prevalence of multi-site work-related musculoskeletal disorders (WMSDs) and their influencing factors among workers in the chemical pharmaceutical industry. {L-End}Methods A total of 563 workers from three chemical pharmaceutical factories in Guangzhou City were selected as the research subjects using the judgment sampling method. The prevalence of multi-site WMSDs in the past 12 months was investigated using the electronic questionnaire of Chinese Version of Musculoskeletal Disorders Questionnaire. {L-End}Results The prevalence of multi-site WMSDs in the research subjects was 30.0% (169/563). The results of multivariable logistic regression analysis showed that workers who smoked regularly/frequently and those who had their hands above shoulder level for long periods of time had a lower risk of multi-site WMSDs than those who never/occasionally smoked (all P≤0.05). Workers with a high school, secondary specialty, college degree, or above had a lower risk of multi-site WMSDs than those with a middle school education or below (all P<0.05). The longer the daily working hours, the higher the risk of multiple WMSDs (all P<0.05). Workers with regular/frequently work shifts had a lower risk of multi-site WMSDs than those with none/occasional work shifts (P<0.05). {L-End}Conclusion The prevalence of multi-site WMSDs among workers in the chemical pharmaceutical industry is relatively high. The influencing factors are individual factors, unreasonable work organization and poor ergonomics factors.