OBJECTIVE: To investigate the inhibitory effect of miR-125b-5p on proliferation and migration of osteosarcoma and the role of RAB3D in mediating this effect. METHODS: The expression level of miR-125b-5p was detected by qRT-PCR in a normal bone cell line (hFOB1.19) and in two osteosarcoma OS cell lines (MG63 and HOS). A miR-125b-5p mimic or inhibitor was transfected in the osteosarcoma cell lines via liposome and the changes in cell proliferation and migration were detected with EDU and Transwell experiments. Bioinformatic analysis was conducted for predicting the target gene of miR-125b-5p, and the expression level of RAB3D in hFOB1.19, MG63, and HOS cells was detected by Western blotting. In the two osteosarcoma cell lines transfected with miR-125b-5p mimic or inhibitor, the expression levels of RAB3D mRNA and protein in osteosarcoma cells were examined with qRT-PCR and Western blotting. The effects of RAB3D overexpression, RAB3D knockdown, or overexpression of both miR-125b-5p and RAB3D on the proliferation and migration of cells were assessed using EDU and Transwell experiments. RESULTS: The two osteosarcoma cell lines had significantly lower expression levels of miR-125b-5p (P < 0.05). Bioinformatic analysis predicted that RAB3D was a possible target gene regulated by miR-125b-5p. In osteosarcoma cells, overexpression of miR-125b-5p significantly lowered the expression of RAB3D protein (P < 0.05); inhibiting miR-125b-5p expression significantly decreased RAB3D expression only at the protein level (P < 0.05) without obviously affecting its mRNA level. Modulation of miR-125b-5p and RAB3D levels produced opposite effects on proliferation and migration of osteosarcoma cells, and in cells with overexpression of both miR-125b-5p and RAB3D, the effect of RAB3D on cell proliferation and migration was blocked by miR-125b-5p overexpression (P < 0.05). CONCLUSION Overexpression of miR-125b-5p inhibits the proliferation and migration of osteosarcoma cells by regulating the expression of RAB3D at the post-transcriptional level.
Humans ; Bone Neoplasms/genetics* ; Cell Proliferation ; MicroRNAs/genetics* ; Osteosarcoma/genetics* ; rab3 GTP-Binding Proteins/genetics* ; RNA, Messenger

OBJECTIVE: Aconite is a traditional Chinese herbal medicine that has been found to inhibit the development of liver cancer; however, its exact molecular mechanisms in this process remain unclear. This study explores how aconite aqueous extract (AAE) inhibits hepatocellular carcinoma (HCC). METHODS: An in vivo mouse model of subcutaneous liver cancer was established. After AAE treatment, immunohistochemistry (IHC) was used to determine the effect of AAE on natural killer (NK) cells. Subsequently, C57BL/6 mice were used to establish the subcutaneous tumor model, and a group of these mice were treated with anti-PK163 antibody to remove NK cells, which was verified by flow cytometry and IHC. The effect of AAE on the proliferation of HCC cells in vitro was determined using cell counting kit-8. The effect of AAE on chemokine production in HCC cells was measured using real-time quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The effect of AAE on the migration of NK cells was determined using a transwell assay. Finally, the molecular mechanism was investigated using the Western blotting method. RESULTS: We demonstrated that the ability of AAE to induce overexpression of the cytokine C-C motif chemokine ligand 2 (CCL2) in HCC cells is fundamental to the infiltration of NK cells into the tumor bed. Mechanistically, we found that the upregulation of CCL2 was achieved by the activation of c-Jun N-terminal kinase but not extracellular regulated protein kinase or p38. CONCLUSION Our findings suggest that AAE can be used as an effective immune adjuvant to enhance antitumor immunity by increasing NK cell infiltration into tumors, which could help to improve the efficacy of HCC treatments. Please cite this article as: Yang KD, Zhang X, Shao MC, Wang LN. Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration. J Integr Med. 2023; 21(6): 575-583.
Animals ; Mice ; Carcinoma, Hepatocellular/drug therapy* ; Liver Neoplasms/drug therapy* ; Aconitum ; Ligands ; Mice, Inbred C57BL ; Killer Cells, Natural/metabolism* ; Chemokines/pharmacology* ; Cell Line, Tumor

Consensus ; Critical Illness ; Humans ; Serum Albumin ; Serum Albumin, Human

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.
Animals ; Cell Differentiation ; Flavanones ; Mice ; Mice, Inbred C57BL ; Myelin Sheath/metabolism* ; Oligodendroglia/metabolism* ; Rats ; Remyelination ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism*

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.

Since December 2019, novel coronavirus pneumonia (NCP) has been reported in Wuhan, Hubei Province, and spreads rapidly to all through Hubei Province and even to the whole country. The virus is 2019 novel coronavirus (2019-nCoV), never been seen previously in human, but all the population is generally susceptible. The virus spreads through many ways and is highly infectious, which brings great difficulties to the prevention and control of NCP. Based on the needs of orthopedic trauma patients for emergency surgery and review of the latest NCP diagnosis and treatment strategy and the latest principles and principles of evidence-based medicine in traumatic orthopedics, the authors put forward this expert consensus to systematically standardize the clinical pathway and protective measures of emergency surgery for orthopedic trauma patients during prevention and control of NCP and provide reference for the emergency surgical treatment of orthopedic trauma patients in hospitals at all levels.

Objective: To evaluate the imaging and clinicopathological characteristics of pancreas perivascular epithelioid cell tumors (PEComa). Methods: The clinical data of patients with pancreatic PEComa admitted in Changhai Hospital of Navy Medical University from Nov 2013 to Nov 2017 were retrospectively analyzed. Related literature on PEComa were searched and the image and clinicopathological characteristics were investigated. Results: Two pancreatic PEComa patients were admitted in Changhai Hospital. Twenty-nine PEComa patients were reported in previous literature. A total of 31 cases were detected, including 3 men and 27 women. The onset age of the patients ranged from 17-74 years old with a mean of 48 years old. The lesions were located at the pancreatic head and neck in 20 cases, and at the pancreatic body and tail in 11 cases. 27 cases had a single lesion, and 4 cases had multiple lesions. Tumor diameter ranged from 1.0-11.5 cm with a mean of 4.1 cm. The cystic solid of the lesions was recorded in 23 patients, and 18 cases had solid mass. Pancreatic duct dilation was reported in 21 patients and 14 of them did not have pancreatic duct dilation. Enhancement mode of the lesions was examined in 21 patients, and the enhancement degree of the lesions were higher than that of the pancreas in 16 cases. Conclusions PEComa has a certain imaging characteristic, which could help obtain a preoperative diagnosis.

Objective: To discuss the imaging features of solid-cystic pancreatic neuroendocrine tumors (PNEN). Methods: CT and MRI data of 38 pathologically diagnosed solid-cystic PNEN admitted in Changhai Hospital affiliated with Navy Medical University were retrospectively analyzed. The tumor location, major axis, shape, boundary, solid and cystic proportion, enhancement pattern, condition of cholangiopancreatic duct, vascular invasion, lymph nodes and organs metastasis were recorded, and the imaging features of PNEN were analyzed and summarized. Results: Of 38 PNEN patients, only one case had two lesions including one solid lesion and one solid-cystic lesion, and 37 cases had only one solid cystic lesion including 6 with mainly cystic component and 31 with solid-cystic mixture. 22 of 38 lesions were located in head or neck of pancreas, and 16 were in body or tail of pancreas. The minimum of major axis was 1.1 cm, and the maximum was 13.3 cm, and the average was 5.5 cm. There were 23 round-like tumors, 2 oval tumors, and 13 irregular lesions; 25 lesions with clear margin, 13 with unclear margin. CT scan detected iso- to hypodense lesions, and speckled, nodular, cambered or eggshell calcification in 10 cases. The lesions were mainly manifested as low signal in T₁WI, which were as inhomogeneous high signal and fluid high signal in T₂WI. The solid component of all the lesions was strengthened at different degree after enhancement. 25 lesions showed obvious enhancement that was higher than that of normal pancreatic parenchyma. 13 lesions had no significant contrast enhancement that was similar to or lower than pancreatic parenchyma. 8 patients had mild dilations of main pancreatic duct and 1 case had mild dilation of common bile duct and intrahepatic bile duct. 5 cases were associated with the atrophy of pancreatic parenchyma with different degrees. 5 cases had adjacent organ infiltration, 3 cases had liver metastases and 3 cases had lymph node metastasis, 1 case had celiac axis, splenic artery and superior mesenteric vein invasion. 6 cases were associated with pancreatogenous portal hypertension. Conclusions Solid-cystic pancreatic neuroendocrine tumors can be easily misdiagnosed as other tumors of pancreas. Analyzing imaging characteristics and clinical data can be expected to improve diagnostic accuracy.

Objective: To investigate the prognostic factors of hyperamylasemia following pancreaticoduodenectomy (PD) . Methods: Clinical data of 359 patients were collected prospectively who underwent PD by the same group at Changhai Hospital of Navy Medical University from January 2017 to June 2018.There were 212 males and 147 females.The median age was 63 years old (range: 23 to 82 years old) .According to whether the patient′s serum amylase was greater than 120 U/L at 0 or 1 day after surgery,the patients were divided into hyperamylasemia group and non-hyperamylasemia group. Univariate analysis and multivariate analysis were used to find out the prognostic factors of hyperamylasemia after PD. Results: Of the 359 patients, 238 cases (66.3%) developed hyperamylasemia.The incidence rate of clinically related pancreatic fistula (15.1% vs.2.5%, P<0.01) , grade B/C post pancreatectomy hemorrhage (8.8% vs. 2.5%, P<0.01) , and surgical site infection (9.2% vs. 3.3%, P=0.04) was significantly higher in the hyperamylasemia group.The severity of complications (CD grade≥Ⅲ: 11.3% vs.4.1%, P=0.023) and postoperative hospital stay (11 days vs. 9 days, P=0.001) were higher in the hyperamylasemia group.In the multivariate analysis, the main pancreatic duct diameter (MPD) ≤3 mm (OR=4.469, 95% CI: 2.563-7.793, P<0.01) , pathological type of disease (pancreatic cancer or pancreatitis) (OR=0.230, 95% CI: 0.122-0.436, P<0.01) and soft texture of pancreas (OR=3.297, 95%CI: 1.930-5.635, P<0.01) were independent prognostic factors for hyperamylasemia. Conclusions Post-PD hyperamylasemia increased the incidence and severity of postoperative complications after PD.MPD≤3 mm, soft texture of pancreas and pathological type of disease were independent prognostic factors of hyperamylasemia.