This research investigated the impact of Ganoderma lucidum polysaccharides(GLP) on hepatoblastoma HepG2 and Huh6 cell models, as well as KM mouse model with in situ transplanted tumors, so as to provide a theoretical basis for the clinical application of GLP. Cell viability was assessed through the CCK-8 assay, whereas cell proliferation was evaluated by using the BeyoClick~(TM)EdU-488 test. Cell apoptosis was visualized via Hochest 33258 staining, and autophagy was detected through Mrfp-GFP-LC3 dual fluorescence staining. An in situ tumor transplantation model was created by using HepG2 cells in mice, and mice were treated with normal saline and GLP of 100, 200, and 300 mg·kg~(-1) for tumor count calculation and size assessment. Hematoxylin-eosin(HE) staining was used to observe pathological changes in tumor tissue and vital organs(liver, kidney, lung, spleen, and heart). Western blot analysis was conducted to measure the protein expressions of tumor protein P53(P53), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved-caspase-3, Beclin-1, autophagy related protein-5(Atg-5), microtubule-associated protein-light chain-3Ⅰ(LC3Ⅰ)/LC3Ⅱ, autophagy adapter protein 62(P62), protein kinase B(Akt), p-Akt, mammalian target of rapamycin(mTOR), and p-mTOR. The in vitro experiment revealed that compared with the control group, after GLP treatment, tumor cell viability decreased significantly; apoptosis rate increased in a dose-dependent manner, and autophagic flux was inhibited. The in vivo experiments showed that compared with the model group, mice treated with GLP exhibited significantly fewer and smaller tumors. Western blot results showed that compared with the control group or model group, levels of P53, Bax, cleaved-caspase-3, Beclin-1, Atg-5, and LC3-Ⅱ/LC3-Ⅰ were significantly increased after GLP treatment, and the levels of Bcl-2, P62, p-Akt/Akt, and p-mTOR/mTOR were significantly decreased. These outcomes suggest that GLP promotes apoptosis and autophagy in hepatoblastoma cells by regulating the Akt/mTOR pathway.
Animals ; Humans ; Autophagy/drug effects* ; Reishi/chemistry* ; Mice ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Liver Neoplasms/genetics* ; Hepatoblastoma/genetics* ; Polysaccharides/pharmacology* ; Cell Line, Tumor ; Signal Transduction/drug effects* ; Male ; Cell Proliferation/drug effects* ; Hep G2 Cells

To enhance the therapeutic efficacy of the baicalin-berberine complex(BA-BBR) in the treatment of ulcerative colitis(UC), BA-BBR nanocrystal microspheres(BA-BBR NC MS) were prepared using the dropping method. The microspheres were characterized in terms of morphology, particle size, differential scanning calorimetry(DSC), and powder X-ray diffraction(XRD). The release profiles of BA and BBR from the microspheres were measured, and the drug release mechanism was investigated. A rat model of UC was induced by 5% dextran sodium sulfate(DSS) and treated continuously for 7 days to evaluate the therapeutic effects of different formulations. The results showed that the prepared BA-BBR MS and BA-BBR NC MS were uniform gel spheres with particle sizes of(1.77±0.16) mm and(1.67±0.08) mm, respectively. After drying, the gels collapsed inward and exhibited a rough surface. During the preparation process, the BA-BBR nanocrystals(BA-BBR NC) were uniformly encapsulated within the microspheres. The release profiles of the microspheres followed a first-order kinetic model, and the 12-hour cumulative release of BA and BBR from BA-BBR NC MS was higher than that from BA-BBR MS. Compared with BA-BBR, BA-BBR NC, and BA-BBR MS, BA-BBR NC MS further alleviated UC symptoms in rats, most significantly reducing the levels of TNF-α, IL-1β, IL-6, and MPO, while increasing the level of IL-4 in colon tissues. These results indicate that BA-BBR NC MS, based on a "nano-in-micro" design, can deliver BA-BBR to the intestine and exert significant therapeutic effects in a UC rat model, suggesting it as a promising new strategy for the treatment of UC.
Animals ; Colitis, Ulcerative/metabolism* ; Rats ; Nanoparticles/chemistry* ; Microspheres ; Male ; Berberine/administration & dosage* ; Flavonoids/administration & dosage* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Particle Size ; Tumor Necrosis Factor-alpha/immunology* ; Drug Liberation ; Drug Compounding

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

In order to explore the medical and social problems related to postoperative lymphedema in breast cancer patients, improve the compliance of rehabilitation treatment and help patients return to society. The self-designed questionnaire was used to investigate 76 patients who met the criteria of lymphedema after breast cancer and refused or failed to adhere to rehabilitation threapy. According to the relevant measurement scale theory and method, the computer-aided software was used to analyze the data to find out the problem and analyze the cause. The prominent problems of poor compliance in patients with breast cancer after operation were successively: subjective factors, objective factors, family social and ethical factors, multidisciplinary factors, hospital management and policy issues. For the above ethical problems, we should adopt positive coping strategies to increase the compliance of patients and improve their quality of life.

Objective:To compare the safety and efficacy of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) for the treatment of biliary obstruction at different locations.Methods:From January 2016 to June 2021 data of 82 patients with obstructive jaundice treated with EUS-HGS in Nanjing Drum Tower Hospital were reviewed in this retrospective cohort study. According to the location of biliary obstruction,patients were divided into hilar biliary obstruction group ( n=30) and distal biliary obstruction group ( n=52). Univariate and multivariate logistic regression analyses were conducted adjusting covariates to compare the technical success rate, the clinical success rate, the adverse reaction incidence, hospital stay and cost of the two groups. Results:The technical success rates were 93.3% (28/30) and 94.2% (49/52) in the hilar biliary obstruction group and the distal biliary obstruction group with no significant difference between the two groups ( P=0.870, OR=1.17, 95% CI: 0.18-7.41). The clinical success rates were 83.3% (25/30) and 88.5% (46/52) in the hilar biliary obstruction group and the distal biliary obstruction group with no significant difference between the two groups ( P=0.514, OR=1.53, 95% CI: 0.43-5.53). The incidence of adverse events in hilar biliary obstruction group was 10.0% (3/30), including cholangitis 3.3% (1/30), biliary fistula 6.7% (2/30), biliary peritonitis 6.7% (2/30). The incidence of adverse events in patients with distal biliary obstruction was 17.3% (9/52), including cholangitis 9.6% (5/52), biliary fistula 7.7% (4/52) and biliary peritonitis 5.8% (3/52). There was no significant difference in the incidence of adverse events between the two groups ( P>0.05). Conclusion:There is no significant difference in safety or efficacy of EUS-HGS for hilar biliary obstruction and distal biliary obstruction.

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.
Male ; Adult ; Humans ; Prognosis ; Retrospective Studies ; Myeloid Differentiation Factor 88 ; China/epidemiology* ; Testicular Neoplasms/drug therapy* ; Cyclophosphamide ; Rituximab/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Prednisone/therapeutic use* ; Doxorubicin/therapeutic use* ; Vincristine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Immediate-Early Proteins/therapeutic use* ; Tumor Suppressor Proteins

OBJECTIVE: To explore the clinical value of three-dimensional (3D) visualization technique in laparoscopic D3 radical resection of right colon cancer. METHODS: We retrospectively analyzed the clinical data of 73 patients with right colon cancer undergoing laparoscopic D3 radical operation in our hospital between May, 2019 and March, 2021. Among these patients, 41 underwent enhanced CT examination with 3D visualization reconstruction to guide the actual operation, and 32 underwent enhanced CT examination only before the operation (control group). In 3D visualization group, we examined the coincidence rate between the 3D visualization model and the findings in surgical exploration of the anatomy and variations of the main blood vessels, supplying vessels of the tumor, and the tumor location, and the coincidence rate between the actual surgical plan for D3 radical resection of right colon cancer and the plan formulated based on the 3D model. The operative time, estimated blood loss, unexpected injury of blood vessels, number of harvested lymph nodes, mean time of the first flatus, complications, postoperative hospital stay and postoperative drainage volume were compared between the two groups. RESULTS: The operative time was significantly shorter in 3D visualization group than in the control group (P < 0.05). The volume of blood loss, proportion of unexpected injury of blood vessel, the number of harvested lymph nodes, time of the first flatus, proportion of complications, postoperative hospital stay and postoperative drainage volume did not differ significantly between the two groups (P > 0.05). In the 3D visualization group, the 3D visualization model clearly displayed the shape and direction of the colon, the location of the tumor, the anatomy and variation of the main blood vessels and the blood vessels supplying the cancer, and showed a coincidence rate of 100% with the findings by surgical exploration. The surgical plan for D3 radical resection of right colon cancer was formulated based on the 3D model also showed a coincidence rate of 100% with the actual surgical plan. CONCLUSION The 3D visualization reconstruction technique allows clear visualization the supplying arteries of the tumor and their variations to improve the efficiency, safety and accuracy of laparoscopic D3 radical resection of right colon cancer.
Colonic Neoplasms/surgery* ; Flatulence/surgery* ; Humans ; Imaging, Three-Dimensional ; Laparoscopy/methods* ; Lymph Node Excision/methods* ; Postoperative Complications ; Retrospective Studies ; Treatment Outcome

Objective To explore the expression and significance of serum DKK1 in patients with gastric cancer. Methods We selected 170 gastric cancer patients (gastric cancer group) and 170 subjects with non-gastric cancer during the same period (control group). ELISA was used to detect the DKK1 level. The ROC curve was used to evaluate the diagnostic performance, and we analyzed the relation between DKK1 level and age, gender, family history of gastric cancer, cigarette smoking, alcohol consumption, tumor size, TNM stage, infiltration depth, lymph node metastasis, liver metastasis, vascular invasion, perineural invasion. Results The serum DDK1 level in GC patients was higher than that in control group (P < 0.0001). ROC curve showed that the possible optimal cut-off value of DKK1 for gastric cancer patients was 167.8 pg/ml, AUC was 0.908, sensitivity was 80.59%, and specificity was 84.71%. There was no significant relation between the serum DKK1 level and age, gender, family history of gastric cancer, cigarette smoking, alcohol consumption, tumor size, liver metastasis, vascular invasion or distant metastasis (all P > 0.05). However, DKK1 level was significantly related with TNM stage, infiltration depth, lymph node metastasis and perineural invasion (all P < 0.05). Conclusion Serum DKK1 level is higher in gastric cancer patients than that of control group and related with the severity of lesions, which indicates that serum DKK1 may be a potential biomarker for gastric cancer screening.

Aim To explore the roles of miRNA-132 and its related proteins(Mecp2, CREB)in the mechanism of methamphetamine(MA)-induced neurotoxicity and dependence.Methods The rats were intraperitioneally injected(ip)with MA(10 mg·kg-1·d-1)to establish methamphetamine dependence model with different dependent time courses of 1 week, 2 weeks, and 4 weeks respectively.The miRNA-132 and Mecp2 mRNA were detected by RT-qPCR, and the Mecp2, p-Mecp2, CREB and p-CREB proteins were detected by Western blot in the tissues of frontal cortex and hippocampus.Results In the frontal cortex, the miRNA-132 and Mecp2 mRNA were up-regulated in MA-dependent groups(P<0.05 and P<0.01), while the Mecp2 protein were down-regulated(P<0.01).MA could promote the phosphorylation of Mecp2 protein in the frontal cortex(P<0.01).In hippocampus, the miRNA-132 was down-regulated in the MA-dependent groups, but Mecp2 mRNA was up-regulated(P<0.05).Mecp2 protein increased in MA-dependent 1 week group(P<0.05), and then recovered with the prolonged time of MA dependence, then decreased in MA-dependent 4 weeks groups(P<0.05)in hippocampus.The phosphorylation level of Mecp2 was significantly decreased in the 1 week group(P<0.01), and then increased in the 2 weeks group(P<0.01)in hippocampus.Conclusions MA could induce an abnormal expression of miRNA-132 in the frontal cortex and hippocampus, and miRNA-132 might inhibit the translation of Mecp2 mRNA and induce the decrease expression of Mecp2 protein in the frontal cortex.But in hippocampus, miRNA-132 does not show the correlation with the Mecp2 expression trend of the frontal cortex.And miRNA-132 regulation does not depend on the expression of Mecp2 in hippocampus.

In order to explore the medical and social problems related to postoperative lymphedema in breast cancer patients, improve the compliance of rehabilitation treatment and help patients return to society. The self-designed questionnaire was used to investigate 76 patients who met the criteria of lymphedema after breast cancer and refused or failed to adhere to rehabilitation threapy. According to the relevant measurement scale theory and method, the computer-aided software was used to analyze the data to find out the problem and analyze the cause. The prominent problems of poor compliance in patients with breast cancer after operation were successively: subjective factors, objective factors, family social and ethical factors, multidisciplinary factors, hospital management and policy issues. For the above ethical problems, we should adopt positive coping strategies to increase the compliance of patients and improve their quality of life.