OBJECTIVE: To observe the effect of acupuncture on chondrocyte autophagy in rats of knee osteoarthritis (KOA) and explore its underlying mechanisms. METHODS: Forty male SPF-grade SD rats were randomized into a blank group, a model group, a suspension group, an acupuncture group, and a combined therapy group, 8 rats in each one. Except the blank group, KOA model was prepared by the injection with papain. The suspension exercise therapy (10 min each time, three times daily), acupuncture (at "Yanglingquan" [GB34], "Zusanli" [ST36], and "Dubi" [ST35] on the right side, 30 min each intervention, once daily) and the combined therapy (the suspension exercise therapy combined with acupuncture) were delivered in the suspension group, the acupuncture group and the combined therapy group, respectively. The intervention of each group was performed continuously for 6 days, and 4 consecutive weeks, at the interval of 1 day. Before and after intervention, Lequesne MG score was assessed in the rats. After intervention, HE staining was adopted to observe the cartilaginous tissue morphology of the right knee joints, and Mankin score was evaluated; the serum levels of interleukin (IL)-1β, IL-6, and tumor neurosis factor-α (TNF-α) were measured using ELISA; the real-time PCR was provided to determine the mRNA expression of collagen protein type Ⅱ(COL2), collagen protein type Ⅹ (COL10), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), and autophagy-regulated protein (Beclin-1) in the cartilaginous tissue of the right knee joint; Western blot was employed to detect the protein expression of PI3K, phosphorylated PI3K (p-PI3K), Akt, phosphorylated Akt (p-Akt), mTOR, phosphorylated mTOR (p-mTOR) and Beclin-1 in the cartilaginous tissue of the right knee joint. RESULTS: Compared with the blank group, the rats in the model group showed the higher Lequesne MG score (P<0.01), thinner cartilage of the right knee, reduced chondrocytes and disordered arrangement, and higher Mankin score (P<0.01). Besides, in the model group, the serum levels of IL-1β, IL-6 and TNF-α were elevated (P<0.01), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 decreased (P<0.01), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR increased (P<0.01) in the cartilaginous tissue of the right knee joint. Compared with the model group, in the suspension group, the acupuncture group and the combined therapy group, the Lequesne MG scores were reduced (P<0.01), the cartilage of the right knee was thickened, the arrangement of chondrocytes was improved, and the Mankin scores were lower (P<0.01). Besides, in these intervention groups, the serum levels of IL-1β, IL-6 and TNF-α were reduced (P<0.01), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 increased (P<0.05, P<0.01), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR decreased (P<0.05, P<0.01) in the cartilaginous tissue of the right knee joint. When compared with the suspension group and the acupuncture group, in the combined therapy group, the Lequesne MG score was reduced (P<0.01), and the Mankin score was reduced (P<0.05, P<0.01). Besides, the serum levels of IL-1β, IL-6 and TNF-α were reduced (P<0.05), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 increased (P<0.05), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR decreased (P<0.05, P<0.01) in the cartilaginous tissue of the right knee joint. CONCLUSION Acupuncture can promote cartilage regeneration of knee joint and autophagy in KOA rats, alleviate inflammation, so as to retard cartilage degeneration, which may be possibly associated with the PI3K/Akt/mTOR signaling pathway.
Animals ; Male ; Acupuncture Therapy ; Proto-Oncogene Proteins c-akt/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Osteoarthritis, Knee/physiopathology* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Signal Transduction ; Rats, Sprague-Dawley ; Chondrocytes/metabolism* ; Humans ; Autophagy ; Acupuncture Points

BACKGROUND:miRNAs expression has been reported to be associated with hepatic and renal fibrosis,and dermal fibrogenesis. Moreover,a targeted regulatory relationship between miR-192-5p and epidermal regulators has been demonstrated in gouty arthritis.OBJECTIVE:To investigate the expression and regulatory role of miR-192-5p in hypertrophic scar and to verify whether there is a targeted regulatory relationship between miR-192-5p and epidermal regulators. METHODS:(1) Six cases of hypertrophic scar tissue and six cases of normal skin tissue were collected from the First Affiliated Hospital of Xinjiang Medical University. And miR-192-5p and epidermal regulator mRNA expression were detected by qRT-PCR. (2) The primary hypertrophic scar fibroblasts were obtained using tissue explant method and cultured to 3-6 generations for subsequent experiments. There were three groups in the experiment:negative control group,miR-192-5p mimic group and miR-192-5p inhibitor group. The latter two groups were transfected with the corresponding sequences. Cell proliferation viability was detected by the cell counting kit-8 assay and EdU kit;and the migration ability was detected by the cell scratch test. Cell apoptosis was detected by flow cytometry. The gene and protein expressions of epidermal regulator,type Ⅰ collagen,type Ⅲ collagen and α-smooth muscle actin were detected by qRT-PCR and western blot,respectively. miR-192-5p targets were predicted by a bioinformatics website,and target binding was validated by dual luciferase assay. RESULTS AND CONCLUSION:(1) Compared with normal skin tissues and their fibroblasts,miR-192-5p and epidermal regulator were highly expressed in hypertrophic scar and hypertrophic scar fibroblasts (P<0.05 or P<0.01). (2) After overexpression of miR-192-5p,cell proliferation was enhanced (P<0.05) and EdU positive cell rate increased (P<0.01) when compared with the negative control group;after inhibition of miR-192-5p,cell viability (P<0.05) and EdU positive rate decreased (P<0.05). (3) At 24 hours after overexpression of miR-192-5p,compared with the negative control group,the area between cell scratches and apoptosis rate decreased in the miR-192-5p mimic group (P<0.05) but increased in the miR-192-5p inhibitor group (P<0.01). (4) At 48 hours after transfection,the mRNA and protein levels of epidermal regulator were significantly decreased in the miR-192-5p mimic group,while the mRNA and protein levels of type Ⅰ collagen,type Ⅲ collagen and α-smooth muscle actin were significantly increased (P<0.05 or P<0.01). The miR-192-5p inhibitor group showed opposite changes in the above four indicators (P<0.05 or P<0.01). (5) The Targetscan website predicted that epidermal regulator had a potential binding site for miR-192-5p. (6) Dual luciferase assays showed that miR-192-5p could bind to epidermal regulator in a targeted manner. To conclude,overexpression of miR-192-5p can decrease the expression of epidermal regulator,and the two may be negatively regulated,suggesting that regulation of epidermal regulator may play a role in inhibiting the proliferation of hypertrophic scar fibroblasts.

In the musculoskeletal system(MSK),bone cortex,tendons,ligaments and meniscus components occupy a large proportion,and the transverse relaxation time of these tissues is extremely short,which makes it impossible for conventional MR sequences to detect their signals.In recent years,the newly developed ultrashort echo time(UTE)and zero echo time(ZTE)sequences have greatly expanded the application of MRI in the MSK by achieving direct imaging of short T2 tissues through sub-millisecond echo time sampling.The current application status and future perspectives of UTE/ZTE in MSK were reviewed in this article.

Objective To construct a predictive model for delayed neurological sequelae(DNS)following acute carbon monoxide poisoning(ACMP)and to verify its efficacy.Methods A retrospective analysis of the gen-eral data of 183 patients with ACMP was conducted.The factors influencing the occurrence of DNS were analyzed using a multivariate Logistic regression model.A corresponding predictive model was then established and its efficacy was verified.Results The multivariate logistic regression model showed that age,smoking history,severe poisoning,blood lactate,time from poisoning to hyperbaric oxygen therapy,and pulmonary infection were independent risk factors for DNS following ACMP(P<0.05).The area under the curve(AUC)of the model for predicting DNS in the development set was 0.933,with a sensitivity of 94.12%and specificity of 89.77%.In the validation set,the AUC was 0.906,with a sensitivity of 90.00%and specificity of 92.68%.The Hosmer-Lemeshow test showed that the predicted probabilities of DNS in both the development and validation sets were not significantly different from the actual probabilities(P>0.05).The predictive model achieved clinical net benefit within the risk threshold ranges of 0.11～0.98 for the development set and 0.12～0.92 for the validation set.Conclusions Age,smoking history,severe poisoning,blood lactate,time from poisoning to hyperbaric oxygen therapy,and pulmonary infec-tion are independent risk factors for DNS following ACMP.The corresponding predictive model has been verified to have good clinical efficacy.

Risk prediction models for postoperative pulmonary complications (PPCs) can assist healthcare professionals in assessing the likelihood of PPCs occurring after surgery, thereby supporting rapid decision-making. This study evaluated the merits, limitations, and challenges of these models, focusing on model types, construction methods, performance, and clinical applications. The findings indicate that current risk prediction models for PPCs following lung cancer surgery demonstrate a certain level of predictive effectiveness. However, there are notable deficiencies in study design, clinical implementation, and reporting transparency. Future research should prioritize large-scale, prospective, multi-center studies that utilize multiomics approaches to ensure robust data for accurate predictions, ultimately facilitating clinical translation, adoption, and promotion.

OBJECTIVE: To evaluate the effectiveness of double joystick technique assisted closed reduction and Kirschner wire internal fixation in the treatment of Gartland type Ⅲ supracondylar fractures of the humerus (SCFH) in children. METHODS: A retrospective study was conducted on 28 cases of Gartland type Ⅲ SCFH with complete data available, who underwent closed reduction and Kirschner wire internal fixation with the double joystick technique between August 2022 and July 2024. There were 23 boys and 5 girls, with an average age of 6.4 years (range, 1-12 years). All fractures resulted from falls and were classified as extension-type. X-ray film showed the radial displacement of the distal fragment in 15 cases and unlar displacement in 13 cases. The interval from injury to operation was 3-36 hours (mean, 19.5 hours). X-ray film re-examination was conducted to evaluate the fracture healing, and the Baumann angle of affected elbow joint and carrying angle of bilateral elbow joints were measured. Elbow joint function was evaluated using the range of motion (flexion and extension) and the Flynn criteria. The above indicators were compared between affected and healthy sides. RESULTS: All operation were successfully completed. The operation time ranged from 15 to 40 minutes (mean, 25.2 minutes). The length of hospital stay was 2-5 days (mean, 3.5 days). All patients were followed up 3-24 months (mean, 11.8 months). X-ray film confirmed fracture healing in all patients, with a mean healing time of 5.4 weeks (range, 4-6 weeks). At last follow-up, the Baumann angle of the affected elbow joint was (73.50±3.46)°, and the carrying angle and the range of motion in flexion and extension of the affected elbow joint were significantly less than the contralateral side (P<0.05). According to the Flynn criteria, the elbow joint function of the affected elbow was evaluated as excellent in 25 cases and good in 3 cases, with an excellent and good rate of 100%. CONCLUSION The double joystick technique is a safe and effective method which can facilitate the closed reduction and Kirschner wire internal fixation of Gartland type Ⅲ SCFH in children without increasing risk of complications.
Humans ; Male ; Female ; Humeral Fractures/diagnostic imaging* ; Fracture Fixation, Internal/instrumentation* ; Child ; Retrospective Studies ; Bone Wires ; Child, Preschool ; Fracture Healing ; Treatment Outcome ; Infant ; Elbow Joint/physiopathology* ; Range of Motion, Articular ; Closed Fracture Reduction/methods*

Objective:To explore the efficacy of atezolizumab combined with anlotinib in treating advanced non-small cell lung cancer (NSCLC) .Methods:A total of 80 patients with advanced NSCLC treated in the Baoding No.2 Central Hospital from September 2019 to September 2023 after second-line treatment were selected as research subjects. Patients who received only anlotinib treatment were included in the monotherapy group ( n=40), while patients who received atezolizumab combined with anlotinib treatment were included in the combination group ( n=40). The clinical efficacy and serum levels of carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF) of the two groups were compared. Kaplan-Meier survival curve was used to analyze the survival of the two groups. The functional assessment of cancer therapy-lung cancer (FACT-L) was used to assess the quality of life of patients in both groups before and after treatment. The incidence of adverse reactions was compared between the two groups. Results:After four cycles of treatment, the objective response rate (ORR) of the combination group was 37.50% (15/40), which was higher than that of the monotherapy group [17.50% (7/40) ], with a statistically significant difference ( χ2=4.01, P=0.045). The disease control rates (DCRs) of the two groups were 85.00% (34/40) and 75.00% (30/40), respectively, with no statistically significant difference ( χ2=1.25, P=0.264). Before treatment, the CEA levels in combination group and monotherapy group were (10.18±2.15) and (10.14±2.02) μg/L, and the VEGF levels were (804.04±46.58) and (809.10±43.63) ng/L, respectively, with no statistically significant difference (both P>0.05). After treatment, the serum CEA levels of patients in combination group and monotherapy group were (4.35±1.05) and (6.63±1.37) μg/L, and the VEGF levels were (431.26±50.19) and (549.92±55.27) ng/L, respectively, with statistically significant differences ( t=8.35, P<0.001; t=10.05, P<0.001), and the levels of serum CEA and VEGF in the two groups after treatment were lower than before treatment ( t=32.47, P<0.001; t=21.73, P<0.001; t=88.65, P<0.001; t=58.27, P<0.001). Survival analysis showed that the median progression-free survival (PFS) of the monotherapy group and the combination group were 4.12 and 6.06 months, respectively, with a statistically significant difference ( χ2=17.70, P<0.001), the median overall survival (OS) were 11.8 and 12.7 months, respectively, with no statistically significant difference ( χ2=3.09, P=0.079). Before treatment, the FACT-L scores of patients in combination group and monotherapy group were 61.20±6.98 and 60.52±7.14, respectively, with no statistically significant difference ( t=0.43, P=0.668). After treatment, the FACT-L scores of the two groups were 83.24±9.38 and 74.58±7.86, respectively, with a statistically significant difference ( t=4.48, P<0.001), and the FACT-L scores of the two groups after treatment were all higher than before treatment ( t=29.36, P<0.001; t=21.51, P<0.001). During treatment, the total incidence of drug-related adverse reactions in two groups was 42.50% (17/40) and 55.00% (22/40), respectively, with no statistically significant difference ( χ2=1.25, P=0.263) . Conclusions:Atezolizumab combined with anlotinib in the treatment of advanced NSCLC can enhance the short-term efficacy, prolong the PFS of patients, improve the quality of life, and the related adverse reactions are tolerable.

Objective To construct a predictive model for delayed neurological sequelae(DNS)following acute carbon monoxide poisoning(ACMP)and to verify its efficacy.Methods A retrospective analysis of the gen-eral data of 183 patients with ACMP was conducted.The factors influencing the occurrence of DNS were analyzed using a multivariate Logistic regression model.A corresponding predictive model was then established and its efficacy was verified.Results The multivariate logistic regression model showed that age,smoking history,severe poisoning,blood lactate,time from poisoning to hyperbaric oxygen therapy,and pulmonary infection were independent risk factors for DNS following ACMP(P<0.05).The area under the curve(AUC)of the model for predicting DNS in the development set was 0.933,with a sensitivity of 94.12%and specificity of 89.77%.In the validation set,the AUC was 0.906,with a sensitivity of 90.00%and specificity of 92.68%.The Hosmer-Lemeshow test showed that the predicted probabilities of DNS in both the development and validation sets were not significantly different from the actual probabilities(P>0.05).The predictive model achieved clinical net benefit within the risk threshold ranges of 0.11～0.98 for the development set and 0.12～0.92 for the validation set.Conclusions Age,smoking history,severe poisoning,blood lactate,time from poisoning to hyperbaric oxygen therapy,and pulmonary infec-tion are independent risk factors for DNS following ACMP.The corresponding predictive model has been verified to have good clinical efficacy.

BACKGROUND:miRNAs expression has been reported to be associated with hepatic and renal fibrosis,and dermal fibrogenesis. Moreover,a targeted regulatory relationship between miR-192-5p and epidermal regulators has been demonstrated in gouty arthritis.OBJECTIVE:To investigate the expression and regulatory role of miR-192-5p in hypertrophic scar and to verify whether there is a targeted regulatory relationship between miR-192-5p and epidermal regulators. METHODS:(1) Six cases of hypertrophic scar tissue and six cases of normal skin tissue were collected from the First Affiliated Hospital of Xinjiang Medical University. And miR-192-5p and epidermal regulator mRNA expression were detected by qRT-PCR. (2) The primary hypertrophic scar fibroblasts were obtained using tissue explant method and cultured to 3-6 generations for subsequent experiments. There were three groups in the experiment:negative control group,miR-192-5p mimic group and miR-192-5p inhibitor group. The latter two groups were transfected with the corresponding sequences. Cell proliferation viability was detected by the cell counting kit-8 assay and EdU kit;and the migration ability was detected by the cell scratch test. Cell apoptosis was detected by flow cytometry. The gene and protein expressions of epidermal regulator,type Ⅰ collagen,type Ⅲ collagen and α-smooth muscle actin were detected by qRT-PCR and western blot,respectively. miR-192-5p targets were predicted by a bioinformatics website,and target binding was validated by dual luciferase assay. RESULTS AND CONCLUSION:(1) Compared with normal skin tissues and their fibroblasts,miR-192-5p and epidermal regulator were highly expressed in hypertrophic scar and hypertrophic scar fibroblasts (P<0.05 or P<0.01). (2) After overexpression of miR-192-5p,cell proliferation was enhanced (P<0.05) and EdU positive cell rate increased (P<0.01) when compared with the negative control group;after inhibition of miR-192-5p,cell viability (P<0.05) and EdU positive rate decreased (P<0.05). (3) At 24 hours after overexpression of miR-192-5p,compared with the negative control group,the area between cell scratches and apoptosis rate decreased in the miR-192-5p mimic group (P<0.05) but increased in the miR-192-5p inhibitor group (P<0.01). (4) At 48 hours after transfection,the mRNA and protein levels of epidermal regulator were significantly decreased in the miR-192-5p mimic group,while the mRNA and protein levels of type Ⅰ collagen,type Ⅲ collagen and α-smooth muscle actin were significantly increased (P<0.05 or P<0.01). The miR-192-5p inhibitor group showed opposite changes in the above four indicators (P<0.05 or P<0.01). (5) The Targetscan website predicted that epidermal regulator had a potential binding site for miR-192-5p. (6) Dual luciferase assays showed that miR-192-5p could bind to epidermal regulator in a targeted manner. To conclude,overexpression of miR-192-5p can decrease the expression of epidermal regulator,and the two may be negatively regulated,suggesting that regulation of epidermal regulator may play a role in inhibiting the proliferation of hypertrophic scar fibroblasts.

In the musculoskeletal system(MSK),bone cortex,tendons,ligaments and meniscus components occupy a large proportion,and the transverse relaxation time of these tissues is extremely short,which makes it impossible for conventional MR sequences to detect their signals.In recent years,the newly developed ultrashort echo time(UTE)and zero echo time(ZTE)sequences have greatly expanded the application of MRI in the MSK by achieving direct imaging of short T2 tissues through sub-millisecond echo time sampling.The current application status and future perspectives of UTE/ZTE in MSK were reviewed in this article.