Background and purpose:Lobaplatin,as a traditional chemotherapeutic drug,is widely used in the treatment of malignant tumor.In recent years,its application in the field of hyperthermic intraperitoneal chemotherapy(HIPEC)has garnered increasing attention.This study evaluated the efficacy and safety of lobaplatin-based HIPEC in advanced abdominal metastatic cancer.Methods:This study collected data of patients with advanced cancers and malignant ascites who treated in the Cancer Center of Shanghai Tenth People's Hospital,Tongji University School of Medicine,from January 2019 to January 2023.We excluded patients who did not meet the inclusion criteria.Short-term efficacy was assessed by changes in ascitic fluid volume,and long-term survival was analyzed using the Kaplan-Meier method.The correlation between CA12-5 levels before and after treatment was evaluated using Pearson correlation analysis.Baseline characteristics and treatment outcomes were described using descriptive statistics,and the changes in CA12-5 levels before and after treatment were compared using significance tests(P＜0.01).Data entry and statistical analyses were conducted using SPSS version 26.0,and survival curves and efficacy plots were generated with GraphPad Prism(10.4.0 version).The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital(Ethics approval number:SHSY-IEC-5.0/24K134/P01).This prospective single-arm study strictly adhered to the guideline of Consolidated Standards of Reporting Trials(CONSORT)checklist.Results:A total of 21 patients were enrolled in this study.The median age of the patients was 61 years(ranging from 31 to 71 years).Among the 21 patients,5(23.8%)achieved complete remission(CR),5(23.8%)achieved partial remission(PR),8(38.1%)had stable disease(SD),and 3(14.3%)experienced disease progression(PD).The overall response rate(ORR)was 47.6%,and the disease control rate(DCR)was 85.7%.Survival analysis revealed a median progression-free survival(PFS)of 12.33 months and a median overall survival(OS)of 16.37 months.Analysis of tumor markers showed a significant negative correlation between efficacy and CA12-5 levels(P＜0.01).Adverse reactions primarily included myelosuppression,hepatic and renal impairment,and nausea and vomiting,with most adverse events being mild to moderate.Conclusion:Lobaplatin-based HIPEC is effective in the treatment of advanced gastrointestinal malignancies with malignant ascites,providing survival benefits and demonstrating good safety.CA12-5 may serve as a valuable predictor of poor prognosis.

BACKGROUND:Internal tension-reduction technique is to reconstruct the anterior cruciate ligament through high-strength suture system combined with tendon.It can effectively reduce graft relaxation and frets by sharing the internal load of the knee joint,and has achieved good biomechanical results and clinical efficacy.However,whether it can reduce cartilage degeneration after anterior cruciate ligament reconstruction through stress sharing reduction has not been studied. OBJECTIVE:To investigate the effect of internal tension-reduction technique on articular cartilage degeneration in southern Yunnan small-ear pigs undergoing anterior cruciate ligament reconstruction. METHODS:Ten adult female Yunnan small-ear pigs were selected,and the ipsilateral knee Achilles tendon was taken from the left knee joint for anterior cruciate ligament reconstruction(normal group,n=10),and the ipsilateral knee Achilles tendon from the right knee joint combined with internal tension-reduction and augmentation system for anterior cruciate ligament reconstruction(tension-reduction group,n=10).One year after surgery,the experimental pigs were sacrificed,and the left and right knee cartilage was taken for hematoxylin-eosin staining,Safranin O-fast green staining,Osteoarthritis Research Society International scoring,and immunohistochemistry staining of type Ⅱ collagen,interleukin-1β,and tumor necrosis factor-alpha in the cartilage. RESULTS AND CONCLUSION:Hematoxylin-eosin staining showed that in the tension-reduction group,there were mild pathologic changes of osteoarthritis,with a low number of empty bone lacunae and no obvious pathological changes such as fibrosis or cell layer breakage;in the normal group,more severe cartilage damage,with an increased number of empty bone lacunae,loss of chondrocytes near the bone and even the formation of fissures.Safranin O-fast green staining indicated that the tension-reduction group had normal cartilage tissue thickness,flat cartilage surface,a neat cell arrangement in a polar pattern,and no swelling or apoptosis,while in the normal group,the thickness of cartilage tissue was obviously thinner,the cell arrangement was disordered with no polarity,the number of cells was reduced,obvious cartilage fractures and cartilage vacuoles formed,and the absence of cells near the central bone was obvious.The Osteoarthritis Research Society International score was significantly lower in the tension-reduction group than in the normal group(P＜0.05).Immunohistochemical findings showed that the protein expression of type Ⅱ collagen in cartilage tissue of the tension-reducing group was higher than that of the normal group(P＜0.05),and the protein expression of interleukin 1β and tumor necrosis factor ɑ in cartilage tissue was lower than that of normal group(P＜0.05).To conclude,internal tension-reduction technique can delay the degeneration of articular cartilage in Yunnan small-eared pigs following anterior cruciate ligament reconstruction.

The consumption of a high-fat diet(HFD)has been linked to osteoporosis and an increased risk of fragility fractures.However,the specific mechanisms of HFD-induced osteoporosis are not fully understood.Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells(BMSCs),diminishing their proliferation and osteogenic capability,and thereby contributes to osteoporosis.Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor(VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice,suggesting that VDR is a key regulator of BMSC senescence.Notably,the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis,bone mass,and other bone parameters.Mechanistically,VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species(ROS)levels and preserving mitochondrial function.Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2(SOD2)-ROS axis.

Background and purpose:Lobaplatin,as a traditional chemotherapeutic drug,is widely used in the treatment of malignant tumor.In recent years,its application in the field of hyperthermic intraperitoneal chemotherapy(HIPEC)has garnered increasing attention.This study evaluated the efficacy and safety of lobaplatin-based HIPEC in advanced abdominal metastatic cancer.Methods:This study collected data of patients with advanced cancers and malignant ascites who treated in the Cancer Center of Shanghai Tenth People's Hospital,Tongji University School of Medicine,from January 2019 to January 2023.We excluded patients who did not meet the inclusion criteria.Short-term efficacy was assessed by changes in ascitic fluid volume,and long-term survival was analyzed using the Kaplan-Meier method.The correlation between CA12-5 levels before and after treatment was evaluated using Pearson correlation analysis.Baseline characteristics and treatment outcomes were described using descriptive statistics,and the changes in CA12-5 levels before and after treatment were compared using significance tests(P＜0.01).Data entry and statistical analyses were conducted using SPSS version 26.0,and survival curves and efficacy plots were generated with GraphPad Prism(10.4.0 version).The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital(Ethics approval number:SHSY-IEC-5.0/24K134/P01).This prospective single-arm study strictly adhered to the guideline of Consolidated Standards of Reporting Trials(CONSORT)checklist.Results:A total of 21 patients were enrolled in this study.The median age of the patients was 61 years(ranging from 31 to 71 years).Among the 21 patients,5(23.8%)achieved complete remission(CR),5(23.8%)achieved partial remission(PR),8(38.1%)had stable disease(SD),and 3(14.3%)experienced disease progression(PD).The overall response rate(ORR)was 47.6%,and the disease control rate(DCR)was 85.7%.Survival analysis revealed a median progression-free survival(PFS)of 12.33 months and a median overall survival(OS)of 16.37 months.Analysis of tumor markers showed a significant negative correlation between efficacy and CA12-5 levels(P＜0.01).Adverse reactions primarily included myelosuppression,hepatic and renal impairment,and nausea and vomiting,with most adverse events being mild to moderate.Conclusion:Lobaplatin-based HIPEC is effective in the treatment of advanced gastrointestinal malignancies with malignant ascites,providing survival benefits and demonstrating good safety.CA12-5 may serve as a valuable predictor of poor prognosis.

The consumption of a high-fat diet(HFD)has been linked to osteoporosis and an increased risk of fragility fractures.However,the specific mechanisms of HFD-induced osteoporosis are not fully understood.Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells(BMSCs),diminishing their proliferation and osteogenic capability,and thereby contributes to osteoporosis.Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor(VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice,suggesting that VDR is a key regulator of BMSC senescence.Notably,the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis,bone mass,and other bone parameters.Mechanistically,VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species(ROS)levels and preserving mitochondrial function.Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2(SOD2)-ROS axis.

Objective To investigate the characteristics of peroperative blood pressure and heart rate in patients with normotensive incidental pheochromocytomas in order to provide the basis for peroperative treatment. Methods This retrospective study collected the data of 104 patients with a pathological diagnosis of unilateral pheochromocytoma at PLA General Hospital during January 2011 to December 2016. They were divided into normotensive incidental pheochromocytomas(NIP) group (n＝50) if the patients were normotensive and HIP group ( n＝54) if the patients were with hypertension. The clinical features, imaging features and peroperative hemodynamics were analyzed. Results ( 1) The age, urinary norepinephrine, daily dosage and duration of phenoxybenzamine in NIP group were less than those of HIP group (all P<0.05). (2) Preinduction blood pressure, maximum blood pressure, and total fluid intake in NIP group were lower than those in HIP group(all P<0.05). The blood pressure range, heart rate range, increased blood pressure, minimum mean arterial pressure, vasoactive medication were without statistical significance between these two groups. ( 3) The times and rate of intraoperative systolic blood pressure more than 30% baseline, 200 mmHg (1 mmHg＝0.133 kPa), 180 mmHg, 160 mmHg, intraoperative tachycardia, bradycardia, intraoperative hypotension and postoperative hypotension were without statistical significance between these two groups. (4) Stratified analysis of age (50 years), phenoxybenzamine (40 mg/d), tumor diameter (50 mm) and preinduction blood pressure (130/80 mmHg) showed that intraoperative blood pressure and heart rate were without statistical significance between these two groups. ( 5) There was no correlation between phenoxybenzamine ( daily dosage or duration ) and peroperative hypotension. Applying phenoxybenzamine or vasoactive medication was not correlated with peroperative hypotension in NIP group. Conclusion The peroperative blood pressure and heart rate of patients with NIP are similar to those of patients with HIP. Adequate peroperative treatment should be applied to NIP to avoid hemodynamic instability.

Objective:To explore the role of Semaphorins 3A(Sema 3A) and its receptor Neuropilin-1 (Nrp1) in the development of chronic periodontitis of rats and clinical samples.Methods:20 SD rats were divided into 2 groups.Rats in the experimental group were induced into chronic periodontitis models.Rats in control group were not treated.After 8 weeks,maxilla of all the rats were collected for micro-CT scanning and IHC staining.The distance from cementoenamel junction to alveolar bone crest(CEJ-ABC) and the IOD of Sema3A/Nrp1 positive staining in rats were analyzed.20 clinical samples of chronic periodontitis(n =10) and normal periodontal tissues (n =10) were collected for immunofluorescence and qRT-PCR analysis.Results:The CEJ-ABC distance of chronic periodontitis group was higher than that of the control group(P ＜ 0.05).The IOD of Sema3A/Nrp1 in experimental group was lower than that of the control group (P ＜ 0.05) and with a negative correlation with bone loss (P ＜ 0.05).Immunofluorescence and qRT-PCR analysis showed that the expression level of Sema3a/Nrpl in clinical samples with chronic periodontitis was also lower than that of the healthy subjects(P ＜ 0.05).Conclusion:The reduced Sema3A/Nrp1 plays an important role in the development of bone destruction in chronic periodontitis.

Objective:To detect the expression levels of neuropilin1 (NRP1)mRNA and miR-9 in non-small cell lung cancer (NSCLC)tissue samples, and to explore the correlations between the expressions of NRP1 mRNA, miR-9 and the clinicopathological characteristics of the patients with NSCLC.Methods:Informed consent was obtained from each patient before surgery.The tissue samples including 45 NSCLC tissue ,45 adjacent carcinoma tissue and 45 normal lung tissue were collected from China-Japan Union Hospital of Jilin University from 2010 to 2011.qRT-PCR was used to detect the expression levels of NRP1 mRNA and miR-9 in three kinds of lung tissue, and the correlation between the expressions of NRP1 mRNA, miR-9 and clinicopathological characteristics of the patients with NSCLC was analyzed.Results:Compared with normal tissue,the expression level of NRP1 mRNA in adjacent carcinoma tissue had no change (P>0.05),but the expression level of NRP1 mRNA in non-small cell lung cancer tissue was significantly decreased (P<0.05).Compared with normal tissue,the expression level of miR-9 in adjacent carcinoma tissue had no change (P>0.05),but the expression level of miR-9 in non-small cell lung cancer tissue was significantly increased (P < 0.05 ). Furthermore, in adjacent carcinoma tissue, the expression level of miR-9 in the males was lower than that in the females (P<0.05 ). In NSCLC tissue, the expression level of NRP1 mRNA had no relationship with sex,age,differentiation degree,TNM stage and clinical stage,but was significantly correlated to the histological subtype and lymph node metastasis (P<0.05).In NSCLC tissue,the expression level of miR-9 had no relationship with age, pathological type, lymph node metastasis, differentiation degree,TNM stage,and clinical stage (P>0.05),but was correlated to the sex (P<0.05). Conclusion:The expression level of miR-9 is up-regulated and the expression level of NRP1 mRNA is down-regulated significantly in non-small cell lung cancer tissue. The detection of the expression level of NRP1 mRNA contributes to j udge the histological subtype and lymph node metastasis of NSCLC.

OBJECTIVE: To investigate the mechanisms for inhibitory effect of aldehyde dehydrogenase 2 (ALDH2) on doxorubicin (DOX)-induced cytotoxicity in C2C12 myogenic cell line.
 METHODS: Cell apoptosis was evaluated by flow cytometry and the activity of capase-3/7. The relative content of reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE) were detected by chemical fluorometric enzyme immunoassay. The protein and mRNA expression of ALDH2, Bcl-2, NADPH oxidase 2 (NOX2) and the cytoplasmic subunit p-p47PHOX were evaluated by Western blot and quantitative PCR, respectively. 
 RESULTS: Overexpression of ALDH2 attenuated DOX-induced cell toxicity (increase in apoptosis and inhibition of proliferation), which were reversed by downregulation of ALDH2. Overexpression of ALDH2 reduced p47PHOX phosphorylation levels, and suppressed activation of NOX2 and ROS production, which were reversed by downregulation of ALDH2. Moreover, apocynin, an inhibitor of NOX, reduced the cytotoxicity of DOX concomitantly with a decrease in phosphorylation of p47PHOX, ROS production and caspase-3/7 activity, and an increase in the activity and expression of ALDH2. 
 CONCLUSION DOX-induced cytotoxicity is related to increase of intracellular oxidative stress, which is involved in unregulation of NOX2 and downregulation of ALDH2. Activation of ALDH2 could exert cytoprotection via inhibiting NOX2-dependent ROS production.
Aldehyde Dehydrogenase, Mitochondrial ; Aldehydes ; Animals ; Apoptosis ; Caspase 3 ; Cell Line ; Cell Survival ; Down-Regulation ; Doxorubicin ; Mice ; Oxidative Stress ; Phosphorylation ; Reactive Oxygen Species