BACKGROUND:Bone marrow mesenchymal stem cells in patients with osteoporosis show significant senescence and decreased activity and osteogenic differentiation.miR-212-3p inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells.However,its regulation of senescence of bone marrow mesenchymal stem cells and its mechanism remain unclear.OBJECTIVE:To investigate the effect of miR-212-3p on senescence of bone marrow mesenchymal stem cells by targeting mitogen-activated protein kinase 3 (MAPK3) and its mechanism.METHODS:Rat bone marrow mesenchymal stem cells were isolated and cultured in vitro,and the third generation was collected for the following experiments:(1) Cultured in two groups:The control group was added with complete culture medium,and the model group was added with complete culture medium containing H2O2.After 72 hours of culture,β-galactosidase activity,miR-212-3p and MAPK3 mRNA expression,as well as MAPK3,p16,and p21 protein expression were detected.(2) Cultured in three groups:control group,inhibitor control group,and miR-212-3p inhibitor group.After transfection for 24 hours,miR-212-3p,mRNA and protein expression of MAPK3 were detected.(3) Dual luciferase reporter gene combined with qRT-PCR and western blot assay were used to verify the targeting regulation of miR-212-3p and MAPK3.(4) Cultured in different groups:control inhibitor group,miR-212-3p inhibitor group,miR-212-3p inhibitor+interference control group,and miR-212-3p inhibitor+MAPK3 interference group.After transfection for 24 hours,MAPK protein and mRNA expression levels in cells were detected.They were divided into control group,H2O2 group,H2O2+control inhibitor group,H2O2+miR-212-3p inhibitor group,H2O2+miR-212-3p inhibitor+interference control group,and H2O2+miR-212-3p inhibitor+MAPK3 interference group.Cells were transfected for 24 hours and then cultured with H2O2 for 72 hours.Aging-related β-galactosidase activity and p16 and p21 protein expression were detected.RESULTS AND CONCLUSION:(1) Compared with the control group,β-galactosidase activity,miR-212-3p mRNA expression and p16,p21 protein expression were increased in the model group (P<0.05),while MAPK3 mRNA and protein expression levels were decreased (P<0.05).(2) Compared with the control group,the mRNA expression of miR-212-3p was decreased (P<0.05),and the mRNA and protein expression levels of MAPK3 were increased (P<0.05) in miR-212-3p inhibitor group.(3) Double luciferase reporter gene experiment confirmed that MAPK3 was the downstream target gene of miR-212-3p.(4) Compared with the control inhibitor group,the mRNA and protein expression levels of MAPK3 were increased in miR-212-3p inhibitor group (P<0.05).Compared with the miR-212-3p inhibitor group,the mRNA and protein expression levels of MAPK3 in the miR-212-3p inhibitor+MAPK3 interference group were decreased (P<0.05).Compared with H2O2+control inhibitor group,β-galactosidase activity in H2O2+miR-212-3p inhibitor group was decreased (P<0.05).Compared with H2O2+miR-212-3p inhibitor group,β-galactosidase activity in H2O2+miR-212-3p inhibitor+MAPK3 interference group was higher than that in H2O2+miR-212-3p inhibitor group (P<0.05).Compared with the H2O2+control inhibitor group,the protein expression levels of p16 and p21 in the H2O2+miR-212-3p inhibitor group were decreased (P<0.05).Compared with H2O2+miR-212-3p inhibitor group,the protein expression levels of p16 and p21 in H2O2+miR-212-3p inhibitor+MAPK3 interference group were increased (P<0.05).(5) To conclude,downregulation of miR-212-3p inhibits the senescence of rat bone marrow mesenchymal stem cells,and its mechanism of action may be achieved by targeting up-regulation of MAPK3 expression.

Objective To investigate the impacts of percutaneous endoscopic interlaminar discectomy(PEID)on pain level and lumbar function in patients with lumbar disc herniation(LDH).Methods From January 2022 to August 2023,84 patients were diagnosed with L4/5 LDH based on clinical data and imaging information were selected as the study subjects.And they were assigned into 42 cases in experimental group and 42 cases in traditional groups complying with treatment methods.The traditional group underwent traditional open approach treatment,while the experimental group underwent PEID.The surgical indicators(including hospitalization time,surgical time,bed rest time,and intraoperative fluoroscopy frequency),the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were compared between the two groups,the visual analogue scale(VAS)score and Oswestry disability index(ODI)were used to quantify the pain level of waist and lower limbs and lumbar function,and the excellent and good rate of clinical satisfaction and the incidence of complications were compared.Results The hospitalization time and bed rest time of the experimental group were obviously shorter than those of the traditional group,while the fluoroscopy frequency was less than that of the traditional group,and surgical time was longer than that of the traditional group,the differences were statistically significant(P＜0.05).After treatment,the pain VAS score and ODI of waist and lower limbs,the IL-6,and TNF-α in the two groups were lower than those before treatment,the experimental group was lower than the traditional group,the differences were statistically significant(P＜0.05).The excellent and good rate of the experimental group and the traditional group were 88.10％and 83.33％,respectively,with no statistically significant difference(P＞0.05).There was no statistically significant difference in the total incidence of complications between the two groups(P＞0.05).Conclusion PEID surgery can effectively alleviate nerve compression,alleviate pain of waist and lower limbs,promote the recovering of lumbar function,and facilitate postoperative recovery in LDH patients.

Objective This study aims to establish a hidden curriculum-based medical humanities teaching pathway within surgical internship education and evaluate its effectiveness in enhancing students' humanistic care competence.Methods A single-group pre-test and post-test design was adopted.A total of 76 interns from a tertiary teaching hospital in 2024 were in-cluded.A five-dimensional hidden curriculum framework—material,spiritual,behavioral,faculty,and institutional—was con-structed.Humanistic competence was assessed before and after the intervention using the Humanistic Professional Awareness Scale for Healthcare Students and Providers(HPAS-HSP).Results Post-intervention scores significantly improved compared to pre-intervention across the total scale in the three dimensions:personal integrity and responsibility,sensitivity to others,and pro-fessional competence(P＜0.05),with the greatest improvement observed in sensitivity to others.Conclusion The structured hidden curriculum is effective in enhancing medical students' humanistic qualities,especially in fostering emotional resonance and professional identity.Future work should focus on verifying behavioral transformation and developing multi-source evaluation sys-tems to improve effectiveness and applicability.

Objective To investigate the impacts of percutaneous endoscopic interlaminar discectomy(PEID)on pain level and lumbar function in patients with lumbar disc herniation(LDH).Methods From January 2022 to August 2023,84 patients were diagnosed with L4/5 LDH based on clinical data and imaging information were selected as the study subjects.And they were assigned into 42 cases in experimental group and 42 cases in traditional groups complying with treatment methods.The traditional group underwent traditional open approach treatment,while the experimental group underwent PEID.The surgical indicators(including hospitalization time,surgical time,bed rest time,and intraoperative fluoroscopy frequency),the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were compared between the two groups,the visual analogue scale(VAS)score and Oswestry disability index(ODI)were used to quantify the pain level of waist and lower limbs and lumbar function,and the excellent and good rate of clinical satisfaction and the incidence of complications were compared.Results The hospitalization time and bed rest time of the experimental group were obviously shorter than those of the traditional group,while the fluoroscopy frequency was less than that of the traditional group,and surgical time was longer than that of the traditional group,the differences were statistically significant(P＜0.05).After treatment,the pain VAS score and ODI of waist and lower limbs,the IL-6,and TNF-α in the two groups were lower than those before treatment,the experimental group was lower than the traditional group,the differences were statistically significant(P＜0.05).The excellent and good rate of the experimental group and the traditional group were 88.10％and 83.33％,respectively,with no statistically significant difference(P＞0.05).There was no statistically significant difference in the total incidence of complications between the two groups(P＞0.05).Conclusion PEID surgery can effectively alleviate nerve compression,alleviate pain of waist and lower limbs,promote the recovering of lumbar function,and facilitate postoperative recovery in LDH patients.

Objective This study aims to establish a hidden curriculum-based medical humanities teaching pathway within surgical internship education and evaluate its effectiveness in enhancing students' humanistic care competence.Methods A single-group pre-test and post-test design was adopted.A total of 76 interns from a tertiary teaching hospital in 2024 were in-cluded.A five-dimensional hidden curriculum framework—material,spiritual,behavioral,faculty,and institutional—was con-structed.Humanistic competence was assessed before and after the intervention using the Humanistic Professional Awareness Scale for Healthcare Students and Providers(HPAS-HSP).Results Post-intervention scores significantly improved compared to pre-intervention across the total scale in the three dimensions:personal integrity and responsibility,sensitivity to others,and pro-fessional competence(P＜0.05),with the greatest improvement observed in sensitivity to others.Conclusion The structured hidden curriculum is effective in enhancing medical students' humanistic qualities,especially in fostering emotional resonance and professional identity.Future work should focus on verifying behavioral transformation and developing multi-source evaluation sys-tems to improve effectiveness and applicability.

OBJECTIVES: Sepsis-associated acute lung injury (S-ALI) is one of the major causes of death in intensive care unit (ICU) patients, yet its mechanisms remain incompletely understood and effective therapies are lacking. Lytic cell death of macrophages is a key driver of the inflammatory cascade in S-ALI. PANoptosis, a newly recognized form of lytic cell death characterized by PANoptosome assembly and activation, involves plasma membrane rupture (PMR) mediated by ninjurin-1 (NINJ1), a recently identified pore-forming protein. Itaconic acid is known for its anti-inflammatory effects, but its role in macrophage PANoptosis during S-ALI is unclear. This study aims to investigate the protective effect of itaconic acid on macrophage PANoptosis in S-ALI to provide new therapeutic insights. METHODS: Male specific-pathogen-free C57BL/6J mice (6-8 weeks, 18-20 g) received intraperitoneal lipopolysaccharide (LPS) to establish a classical S-ALI model. Western blotting was used to assess PANoptosome-related proteins and enzymes involved in the itaconic acid metabolic pathway, while real-time reverse transcription polymerase chain reaction and metabolomics quantified itaconic acid levels. Primary peritoneal macrophages (PMs) were pretreated with the itaconate derivative 4-octyl itaconate (4-OI) and then exposed to tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ) to induce PANoptosis. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Western blotting was employed to quantify enzymes of the itaconate-metabolic pathway in PANoptotic macrophages, to evaluate the impact of 4-OI on PANoptosome-associated proteins, and to determine NINJ1 abundance in lung tissues from S-ALI mice and in PANoptotic macrophages. Fluorescent dye FM_4-64 was used to visualize 4-OI-mediated changes in PMR, whereas immunofluorescence staining mapped the effect of 4-OI on both the expression level and membrane localization of NINJ1 in PANoptotic macrophages. The effect of 4-OI on lactate dehydrogenase (LDH) release in culture supernatants and peripheal blood serum was assessed using a LDH assay kit, and non-denataring polyacylamide gel electrophoresis was used to assess the expression of NINJ1 in S-ALI mouse lung tissues and the impact of 4-OI on the expression of PANoptosis-associated NINJ1 multimeric reflected protein in macropahges. RESULTS: In S-ALI mouse lungs, PANoptosome components [NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Caspase-1, Z-DNA binding protein (ZBP1), and Caspase-3] and phosphorylated mixed lineage kinase domain-like protein (MLKL) S345 were significantly upregulated (all P<0.05), while metabolomics showed compensatory increases in itaconic acid and its key enzymes [aconitate decarboxylase 1 (ACOD1)/immunoresponsive gene 1 (IRG1)]. In macrophages, 4-OI obviously suppressed PANoptosome protein expression, reduced LDH release, restored plasma membrane integrity, and inhibited NINJ1 expression and oligomerization at the membrane (P<0.05). CONCLUSIONS Itaconic acid may alleviate macrophage PANoptosis in S-ALI by inhibiting NINJ1-mediated plasma membrane rupture. Targeting NINJ1 or enhancing itaconate pathways may offer a novel therapeutic strategy for S-ALI.
Animals ; Acute Lung Injury/pathology* ; Succinates/pharmacology* ; Sepsis/complications* ; Mice, Inbred C57BL ; Male ; Mice ; Macrophages/pathology* ; Cell Membrane/metabolism* ; Lipopolysaccharides ; Hydro-Lyases

BACKGROUND:Bone marrow mesenchymal stem cells in patients with osteoporosis show significant senescence and decreased activity and osteogenic differentiation.miR-212-3p inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells.However,its regulation of senescence of bone marrow mesenchymal stem cells and its mechanism remain unclear.OBJECTIVE:To investigate the effect of miR-212-3p on senescence of bone marrow mesenchymal stem cells by targeting mitogen-activated protein kinase 3 (MAPK3) and its mechanism.METHODS:Rat bone marrow mesenchymal stem cells were isolated and cultured in vitro,and the third generation was collected for the following experiments:(1) Cultured in two groups:The control group was added with complete culture medium,and the model group was added with complete culture medium containing H2O2.After 72 hours of culture,β-galactosidase activity,miR-212-3p and MAPK3 mRNA expression,as well as MAPK3,p16,and p21 protein expression were detected.(2) Cultured in three groups:control group,inhibitor control group,and miR-212-3p inhibitor group.After transfection for 24 hours,miR-212-3p,mRNA and protein expression of MAPK3 were detected.(3) Dual luciferase reporter gene combined with qRT-PCR and western blot assay were used to verify the targeting regulation of miR-212-3p and MAPK3.(4) Cultured in different groups:control inhibitor group,miR-212-3p inhibitor group,miR-212-3p inhibitor+interference control group,and miR-212-3p inhibitor+MAPK3 interference group.After transfection for 24 hours,MAPK protein and mRNA expression levels in cells were detected.They were divided into control group,H2O2 group,H2O2+control inhibitor group,H2O2+miR-212-3p inhibitor group,H2O2+miR-212-3p inhibitor+interference control group,and H2O2+miR-212-3p inhibitor+MAPK3 interference group.Cells were transfected for 24 hours and then cultured with H2O2 for 72 hours.Aging-related β-galactosidase activity and p16 and p21 protein expression were detected.RESULTS AND CONCLUSION:(1) Compared with the control group,β-galactosidase activity,miR-212-3p mRNA expression and p16,p21 protein expression were increased in the model group (P<0.05),while MAPK3 mRNA and protein expression levels were decreased (P<0.05).(2) Compared with the control group,the mRNA expression of miR-212-3p was decreased (P<0.05),and the mRNA and protein expression levels of MAPK3 were increased (P<0.05) in miR-212-3p inhibitor group.(3) Double luciferase reporter gene experiment confirmed that MAPK3 was the downstream target gene of miR-212-3p.(4) Compared with the control inhibitor group,the mRNA and protein expression levels of MAPK3 were increased in miR-212-3p inhibitor group (P<0.05).Compared with the miR-212-3p inhibitor group,the mRNA and protein expression levels of MAPK3 in the miR-212-3p inhibitor+MAPK3 interference group were decreased (P<0.05).Compared with H2O2+control inhibitor group,β-galactosidase activity in H2O2+miR-212-3p inhibitor group was decreased (P<0.05).Compared with H2O2+miR-212-3p inhibitor group,β-galactosidase activity in H2O2+miR-212-3p inhibitor+MAPK3 interference group was higher than that in H2O2+miR-212-3p inhibitor group (P<0.05).Compared with the H2O2+control inhibitor group,the protein expression levels of p16 and p21 in the H2O2+miR-212-3p inhibitor group were decreased (P<0.05).Compared with H2O2+miR-212-3p inhibitor group,the protein expression levels of p16 and p21 in H2O2+miR-212-3p inhibitor+MAPK3 interference group were increased (P<0.05).(5) To conclude,downregulation of miR-212-3p inhibits the senescence of rat bone marrow mesenchymal stem cells,and its mechanism of action may be achieved by targeting up-regulation of MAPK3 expression.

Nail-patella syndrome (NPS) is a hereditary rare disease that can involve fingernail, patella, elbow, and iliac bones. In this article, we report a case of a girl-9 and 1 quarter years old who had asthmatic contractures in both elbows, thumbnail hypoplasia in both hands, patellar dislocation of both knees, iliac angle protrusion of both sides, and scoliosis. Whole exome sequencing suggests the presence of a LMX1B NM_002316.4:c.706G > C(p.Ala236Pro) mutation. NPS is an autosomal dominant disease associated with gene mutation of LMX1B, which can be diagnosed by combining the patient′s clinical manifestations and genetic results. The treatment now only targets on symptoms, relieving the localized severe lesion but not cure right now.

Objective:To investigate the application value of Overlap guiding tube (OGT) in Overlap esophagojejunostomy of laparoscopic total gastrectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients with gastric cancer who were admitted to Nanfang Hospital of Southern Medical University from June to July in 2021 were collected. There were 3 males and 2 females, aged from 48 to 61 years, with a median age of 54 years. Patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination and telephone interview to detect postoperative anastomotic stenosis and esophageal reflux up to September 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR) or M(range). Count data were represented as absolute numbers. Results:(1) Surgical situations: 5 patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy and D 2 lymph node dissection success-fully, achieving R 0 resection. There was no combined organ resection, intraoperative conversion to laparotomy or combined thoracotomy. There was no intraoperative conversion to other esophagoje-junostomy method either. The tumor diameter, length of surgical incision, the number of lymph nodes dissected, time of esophagojejunal anastomosis, time of digestive reconstruction, operation time, volume of intraoperative blood loss of 5 patients were 3.0(2.8)cm, 5.0(2.0)cm, 47.0(21.0), 21.0(5.0)minutes, 62.0(23.0)minutes, 295.0(75.0)minutes, and 50.0(60.0)mL, respectively. The anvil fork of linear stapler was successfully inserted into esophageal lumen by once operation in 4 cases of 5 patients and by twice operation in 1 case to complete the esophagojejunostomy. (2) Post-operative situations: the time to first out-of-bed activities, time to postoperative first anal flatus, time to postoperative initial liquid diet intake, time to postoperative initial semi-liquid diet intake, time to abdominal drainage tube removal, duration of postoperative hospital stay of 5 patients were 2.0(1.0)days, 3.0(2.0)days, 4.0(3.0)days, 6.0(3.0)days, 7.0(4.0)days, and 9.0(6.0)days, respectively. Results of postoperative pathological examination of 5 patients showed gastric adenocar-cinoma in all the 5 patients, with the TNM staging as stage pT2-4aN0M0. The esophageal surgical margin was negative in all cases, and the length of proximal margin from esophagus was 5.0(4.0)cm. None of the 5 patients developed anastomotic leakage, anastomotic bleeding or anastomotic stenosis. Two cases with mild pneumonia (Clavien-Dindo grade Ⅱ) were cured by conservative treatment such as anti-infection and expectoration promotion. There was no unplanned secondary surgery or perioperative death occurred to the 5 patients. (3) Follow-up: 5 patients were followed up for 3 months. None of the 5 patients developed anastomotic stenosis or esophageal reflux during the follow-up. Conclusion:OGT-assisted Overlap esophagojejunostomy of laparoscopic total gas-trectomy is safe and feasible, with good short-term effects.

Objective To observe the clinical study of Xiaoaiping tablet combined AP regimen in the treatment of unresectable advance endometrial carcinoma. Methods A total of 268 patients with advance endometrial carcinoma in our hospital were divided into treatment group and control group, 134 cases in each group. The control group was treated by AP regimen and the treatment group was given Xiaoaiping tablet combined AP regimen. The treatment was 3 weeks per course, 4 periods performance, and the 2 year follow-up. After the treatment, the immune index, including IgG, IgA, IgM, CD3+ and CD4+ were detected by a chemical lighting method in the 2 groups. The KPS scores were observed to evaluate the life quality in the 2 groups. During the treatment, the adverse effects of chemotherapy in patients were observated during the treatment. And the survival rates, overall survival and progression-freely-survival were also observed. Results After the treatment, the control rate and efficiency rate were 86.5％ (116/134) and 64.2％(86/134) in treatment group, while the control rate and efficiency rate were 76.9％ (103/134) and 52.2％(70/134) in control group, where there were significantly difference in control rate and efficiency rate (Z values were 3.542 and 3.871, P values were 0.041 and 0.039). After the treatment, the levels of IgG, Ig A, IgM, CD3+ and CD4+ in treatment group were significantly higher than control group (t values were 4.725, 4.930, 4.259, 4.571 and 4.006, P<0.01). After the 1st-4th period of treatment, the KPS scores in treatment group were significantly higher than the control group (t values were 3.124, 3.452, 3.612 and 3.712, P<0.05). After the treatment, the PFS, OS, 1 year survival rate and 2 year survival rate were significantly lower in treatment group than control group (t values were 4.241, 4.421, 3.735 and 3.982, P<0.05). Conclusions The Xiaoaiping tablet combined AP regimen in the treatment of unresectable advance endometrial carcinoma has a good effect, could promote the immune function, decease the adverse effects and prolong the survival time in the patients.