Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.
Male ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Young Adult ; Adult ; Stomach Neoplasms/surgery* ; Peritoneal Neoplasms/secondary* ; Hyperthermic Intraperitoneal Chemotherapy ; Percutaneous Coronary Intervention ; Hyperthermia, Induced/methods* ; Combined Modality Therapy ; Laparoscopy/methods* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Perfusion ; Cytoreduction Surgical Procedures ; Survival Rate

Objective: Differential flora and differential metabolites shared by the intestinal and respiratory tracts of rats were screened to analyze the possible role of changes in intestinal flora and metabolites in the progression of pneumoconiosis in rats. Methods: In April 2020, 18 SD rats were randomly divided into three groups (control group, coal mine dust group and silica group, 6 in each group) , rats in the coal mine dust group and silica group were perfused with 1 ml of 50 mg/ml coal mine well dust suspension and silica suspension by nontracheal exposure, respectively. While rats in the control group were perfused with an equal dose of sterilized normal saline. Twenty four weeks after dust staining, rat feces, throat swabs, and lung lavages were collected. 16SrDNA gene sequencing and UHPLC-QTOF-MS untargeted metabolomics were used to analyze the flora and metabolites in feces, throat swabs and lung lavage fluid of rats in each group, to screen for shared differential flora and shared differential metabolites in intestinal and respiratory tract, and the correlation analysis between the differential flora and metabolites was performed using Spearman's statistics. Results: Compared with the control group, a total of 9 species shared differential flora between intestinal and respiratory tract were screened at phylum level, and a total of 9 species shared differential genus between intestinal and respiratory tract were screened at genus level in the coal mine dust group, mainly Firmicutes, Actinobacteria, Streptococcus, Lactobacillus, etc. Compared with the control group, a total of 9 shared differential flora were screened at the phylum level, and a total of 5 shared differential genus were screened at the genus level in the silica group, mainly Proteobacteria, Actinobacteria, Allobactera, Mucilaginibacter, etc. Compared with the control group, a total of 7 shared differential metabolites were screened for up-regulation of Stigmatellin, Linalool oxide and Isoleucine-leucine in both intestinal and respiratory tract in the coal mine dust group. Compared with the control group , a total of 19 shared differential metabolites werescreened in the silica group, of which Diethanolamine, 1-Aminocyclopropanecarboxylic acid, Isoleucine-leucine, Sphingosine, Palmitic acid, D-sphinganine, 1, 2-dioleoyl-sn-glycero-3-phosphatidylcholine, and 1-Stearoyl-2-oleoyl-sn-glycerol 3-phosphocholine were up-regulated in both the intestinal and respiratory tract. Conclusion: There is a translocation of intestinal and respiratory flora in pneumoconiosis rats, and rats have an imbalance of lipid metabolism during the progression of pneumoconiosis.
Rats ; Animals ; Isoleucine ; Leucine ; Coal Mining ; Rats, Sprague-Dawley ; Pneumoconiosis ; Dust/analysis* ; Silicon Dioxide ; Coal

Objective:To investigate the risk factors of post-stroke depression (PSD) in patients with first acute stroke 6 months after onset.Methods:Three hundred and sixty-seven patients with acute stroke who were treated for the first time in the Affiliated Hospital of Xuzhou Medical University were selected retrospectively. After onset for 6 months, the patients were followed up and divided into PSD group and non-PSD group. The clinical data, blood index, imaging data, degree of nerve damage and the patient's stigma level were compared between the two groups.Results:Totally 182 and 185 cases were included in the PSD and non-PSD groups, respectively. The incidence of PSD at 6 months post-stroke was 49.6% (182/367). The results of univariate analysis showed that diseased region, drinking history, monthly income, standard of culture, serum cortisol, total cholesterol (TC), high sensitivity C-reactive protein (hs-CRP), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), Stigma Scale for Chronic Illness-8 Chronic Disease Stigma Scale-8(SSCI-8) scores, National Institute of Health Stroke Scale (NIHSS) scores and subtype of stroke were risk factors for PSD ( P<0.05). Binary Logistic regression analysis showed that diseased region at frontal lobe ( OR = 3.245, P = 0.011), basal ganglia region ( OR = 2.820, P = 0.007), cerebellar hemisphere ( OR = 4.594, P = 0.010) and serum cortisol ( OR = 1.174, P<0.001), hs-CRP ( OR = 1.057, P<0.001), SSCI-8 scores ( OR = 1.674, P<0.001), NIHSS scores ( OR = 1.283, P<0.001) were independent risk factors for PSD. Conclusions:PSD is a common complication in patients with stroke. Diseased region (at frontal lobe, basal ganglia region, cerebellar hemispheres), hs-CRP, serum cortisol, level of morbidity stigma and degree of neurological impairment are development risk factors for the PSD at 6 months of acute stroke.

Objective:To establish a clinical diagnostic scoring model for preoperative predicting hepatocellular carcinoma (HCC) microvascular invasion (MVI) based on gadolinium-ethoxybenzyl-diethylenetriamine pentacetic acid (Gd-EOB-DTPA) enhanced MRI, and verify its effectiveness.Methods:From January 2014 to December 2020, a total of 251 cases with pathologically confirmed HCC from Tianjin First Central Hospital and Jilin University First Hospital were retrospectively collected to serve as the training set, while 57 HCC patients from Tianjin Medical University Cancer Hospital were recruited as an independent external validation set. The HCC patients were divided into MVI positive and MVI negative groups according to the pathological results. The tumor maximum diameters and apparent diffusion coefficient (ADC) values were measured. On the Gd-EOB-DTPA MRI images, tumor morphology, peritumoral enhancement, peritumoral low intensity (PTLI), capsule, intratumoral artery, intratumoral fat, intratumoral hemorrhage, and intratumoral necrosis were observed. Univariate analysis was performed using the χ 2 test or the independent sample t-test. The independent risk factors associated with MVI were obtained in the training set using a multivariate logistic analysis. Points were assigned to each factor according to the weight value to establish a preoperative score model for predicting MVI. The receiver operating characteristic (ROC) curve was used to determine the score threshold and to verify the efficacy of this scoring model in predicting MVI in the independent external validation set. Results:The training set obtained 98 patients in the MVI positive group and 153 patients in the MVI negative group, while the external validation set obtained 16 patients in the MVI positive group and 41 patients in the MVI negative group. According to logistic analysis, tumor maximum diameter>3.66 cm (OR 3.654, 95%CI 1.902-7.018), hepatobiliary PTLI (OR 9.235, 95%CI 4.833-16.896) and incomplete capsule (OR 6.266, 95%CI 1.993-9.345) were independent risk factors for MVI in HCC, which were assigned scores of 3, 4 and 2, respectively. The total score ranged from 0 to 9. In the external validation set, ROC curve analysis showed that the area under the curve of the scoring model was 0.918 (95%CI 0.815-0.974, P=0.001). When the score>4 was used as the threshold, the accuracy, sensitivity, and specificity of the model in predicting MVI were 84.2%, 81.3%, and 85.4%, respectively. Conclusions:A scoring model based on Gd-EOB-DTPA-enhanced MRI provided a convenient and reliable way to predict MVI preoperatively.

Objective:To compare the efficacy and safety of retroperitoneal laparoscopic adrenalectomy (RLA) and transperitoneal laparoscopic adrenalectomy (TLA) in the treatment of localized adrenocortical carcinoma (ACC).Methods:The data of 22 patients with stage Ⅰ/Ⅱ ACC underwent laparoscopic adrenalectomy in our institution from January 2009 to December 2018 were retrospectively analyzed. According to the different surgical approaches, these patients were divided into RLA and TLA groups. Eleven patients underwent RLA and 11 patients underwent TLA. There were no significant differences between the RLA group and the TLA group in terms of age at first diagnosis[44 (35, 54) vs. 46(41, 55) years, P= 0.793], sex (male/female: 3/8 vs. 4/7, P = 1.00), secreting tumor ratio (3/11 vs. 4/11, P = 1.00), tumor location (left/right: 6/6 vs. 7/4, P = 1.00), with hypertension or diabetes mellitus (4/11 vs. 3/11, P = 1.00). However, RLA has significantly smaller tumor size [3.0(2.5, 8.4) cm vs. 7.7(5.2, 8.4)cm, P= 0.001], and more stage Ⅰ patients [90.9%(10/11) vs. 18.2%(2/11), P=0.002], compared with those in TLA group. The perioperative indicators and oncology prognosis outcomes were collected and compared between the two groups. The Kaplan-Meier method was performed to calculate the overall survival (OS) and disease-free survival (DFS). Results:Compared with TLA, RLA had shorter operation time[90(70, 100) vs. 110 (90, 120) min, P = 0.005] and postoperative drainage tube removal time [2 (2, 3) vs. 3 (2, 6) day, P = 0.002), and the difference was statistically significant. In the TLA group, one patient was converted to open operation due to intraoperative tumor capsule rupture. For postoperative complications, one patient in the TLA group suffered with wound infection. There were no perioperative deaths in either group. All postoperative pathological examinations confirmed ACC, and there was no significant difference in Ki-67 index between the two groups [10%(3%, 35%) vs. 10%(9%, 25%), P = 0.484]. The median follow-up was similar in the two groups [48(26, 98) vs. 31(18, 49) months, P=0.237]. The local recurrence and metastasis rates were 36.4% for RLA group and 63.6% for TLA group ( P = 0.395). Survival analysis showed no statistically significant difference in DFS [5-year DFS rate: 33.6% vs. 73.2%, P = 0.118] between the two groups. The 5-year OS rates for RLA group versus TLA group were 58.3% vs. 45.5% ( P=0.485). Conclusions:For localized (stage Ⅰ/Ⅱ) ACC, both RLA and TLA seem safe and feasible, based on the similar long-term oncological prognosis. However, compared with TLA, RLA has the advantage of shorter operation time and postoperative drainage tube removal time. Due to the small number of cases included in this study, further multi-center, large-sample studies are required to demonstrate clear benefit of one surgical approach in the future.