Clusterin is upregulated by erastin, a ferroptosis inducer and exerts cytoprotective effects in pancreatic adenocarcinoma cells.

Ferroptosis is a novel form of cell death, which is distinguished from apoptosis and necrosis, and characterized by accumulation of lipid-based reactive oxygen species (ROS) in an iron-dependent manner. Erastin, a small molecule, was widely reported to trigger ferroptosis in various kinds of cancer cells, including pancreatic cancer cells by inducing ROS accumulation. However, how erastin treatment exerts cytotoxicity is not still fully understood. In this study, the effects of erastin in causing pancreatic cancer cell death via inducing ferroptosis and apoptosis are investigated. As expected, erastin treatment caused ROS accumulation, increase in iron concentration and non-apoptotic cell death, which is different from that of induced by apoptosis inducer, staurosporine. Interestingly, erastin treatment caused the upregulation of clusterin, which contributes to the regulation of malignant behaviors of pancreatic cancer, including preventing apoptosis and inducing chemoresistance. Without erastin treatment, overexpressed clusterin significantly promoted cell proliferation, which is consistent with its cytoprotective roles. After erastin treatment, overexpressed clusterin decreased erastin-induced ROS accumulation and cell death. By measuring iron concentration, reduced glutathione (GSH) and glutathione peroxidase 4 (GPX4), it is revealed that clusterin caused resistance to erastin-induced ferroptosis potentially via maintaining the enzymatic activity of GPX4, without disturbing GSH amount. Thus, ferroptosis inducer, erastin, may crosstalk with apoptotic cell death via regulating clusterin, indicating a more complex regulatory network between ferroptosis and apoptosis.

MEX3A knockdown inhibits the development of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is one of the most serious causes of death in the world due to its high mortality and inefficacy treatments. MEX3A was first identified in nematodes and was associated with tumor formation and may promote cell proliferation and tumor metastasis. So far, nothing is known about the relationship between MEX3A and PDA. METHODS: In this study, the expression level of MEX3A in PDA tissues was measured by immunohistochemistry. The qRT-PCR and western blot were used to identify the constructed MEX3A knockdown cell lines, which was further used to construct mouse xenotransplantation models. Cell proliferation, colony formation, cell apoptosis and migration were detected by MTT, colony formation, flow cytometry and Transwell. RESULTS: This study showed that MEX3A expression is significantly upregulated in PDA and associated with tumor grade. Loss-of-function studies showed that downregulation of MEX3A could inhibit cell growth in vitro and in vivo. Moreover, it was demonstrated that knockdown of MEX3A in PDA cells promotes apoptosis by regulating apoptosis-related factors, and inhibits migration through influencing EMT. At the same time, the regulation of PDA progression by MEX3A involves changes in downstream signaling pathways including Akt, p-Akt, PIK3CA, CDK6 and MAPK9. CONCLUSIONS: We proposed that MEX3A is associated with the prognosis and progression of PDA,which can be used as a potential therapeutic target.

Super air stable quasi-2D organic-inorganic hybrid perovskites for visible light-emitting diodes.

Solution processed organic-inorganic hybrid perovskites are emerging as a new generation materials for optoelectronics. However, the electroluminescence is highly limited in light emitting diodes (LED) due to the low exciton binding energy and the great challenge in stability. Here, we demonstrate a super air stable quasi-two dimensional perovskite film employing hydrophobic fluorine-containing organics as barrier layers, which can store in ambient for more than 4 months with no change. The dramatically reduced grain size of the perovskite crystal in contrast to three dimensional (3D) perovskites was achieved. Together with the natural quantum well of quasi-two dimensional perovskite confining the excitons to recombination, the LED exhibited the maximum luminance of 1.2 × 103 cd/m2 and current efficiency up to 0.3 cd/A, which is twenty fold enhancement than that of LED based on 3D analogues under the same condition.

Short-term outcomes and risk factors for pancreatic fistula after pancreatic enucleation: A single-center experience of 142 patients.

BACKGROUND: Enucleation is increasingly used for benign or low-grade pancreatic neoplasms. Enucleation preserves the pancreatic parenchyma as well as decreases the risk of long-term endocrine and exocrine dysfunction, but may be associated with a higher rate of postoperative pancreatic fistula (POPF). The aim of this study was to assess short-term outcomes, in particular, POPF. METHODS: Data were collected retrospectively from all 142 patients who underwent pancreatic enucleation between 2009 and 2014 in our institution were analyzed. RESULTS: Lesions were most frequently located in the head and uncinate process of the pancreas (60.6%), and the most common types were neuroendocrine neoplasms (52.1%). Overall morbidity was 66%, mainly due to POPF (53.5%), and severe morbidity was only 8.4%, including one death (0.7%). Clinical POPF (Grade B or C) occurred in 22 patients (15.5%). Independent risk factors for clinical POPF were age ≥60 years, an episode of acute pancreatitis, and cystic morphology. Tumor size, coverage, histological differentiation, and prolonged operative time were not associated with the risk of POPF. CONCLUSIONS: Enucleation is a safe and feasible procedure for benign or low-grade pancreatic neoplasms. The rate of clinical POPF is acceptable, and clinical POPF occurs more frequently in elderly patients (≥60 years of age), patients with cystic neoplasms, or patients with an episode of acute pancreatitis.

Lidocaine Induces Apoptosis and Suppresses Tumor Growth in Human Hepatocellular Carcinoma Cells In Vitro and in a Xenograft Model In Vivo.

BACKGROUND: Recent epidemiologic studies have focused on the potential beneficial effects of regional anesthetics, and the differences in cancer prognosis may be the result of anesthetics on cancer biologic behavior. However, the function and underlying mechanisms of lidocaine in hepatocellular carcinoma both in vitro and in vivo have been poorly studied. METHODS: Human HepG2 cells were treated with lidocaine. Cell viability, colony formation, cell cycle, and apoptosis were assessed. The effects of lidocaine on apoptosis-related and mitogen-activated protein kinase protein expression were evaluated by Western blot analysis. The antitumor activity of lidocaine in hepatocellular carcinoma with or without cisplatin was investigated with in vitro experiments and also with animal experiments. RESULTS: Lidocaine inhibited the growth of HepG2 cells in a dose- and time-dependent manner. The authors also found that lidocaine arrested cells in the G0/G1 phase of the cell cycle (63.7 ± 1.7% vs. 72.4 ± 3.2%; P = 0.0143) and induced apoptosis (1.7 ± 0.3% vs. 5.0 ± 0.7%; P = 0.0009). Lidocaine may exert these functions by causing an increase in Bax protein and activated caspase-3 and a corresponding decrease in Bcl-2 protein through the extracellular signal-regulated kinase 1/2 and p38 pathways. More importantly, for the first time, xenograft experiments (n = 8 per group) indicated that lidocaine suppressed tumor development (P < 0.0001; lidocaine vs. control) and enhanced the sensitivity of cisplatin (P = 0.0008; lidocaine plus cisplatin vs. cisplatin). CONCLUSIONS: The authors' findings suggest that lidocaine may exert potent antitumor activity in hepatocellular carcinoma. Furthermore, combining lidocaine with cisplatin may be a novel treatment option for hepatocellular carcinoma.

Undifferentiated (spindle cell) pancreatic carcinoma: a case report with osteochondroid differentiation.

CONTEXT: Undifferentiated (spindle cell) carcinomas of the pancreas are rare anaplastic variants of pancreatic ductal adenocarcinoma with a frequency of 2% of pancreatic exocrine tumors. Their clinicopathological features are limited and obtained by few previously case reports. We report a case of undifferentiated pancreatic carcinoma with a rare focal osteochondroid differentiation. CASE REPORT: A sixty-six-year-old woman was admitted to our hospital for abdominal pain and nonspecific nausea for almost 40 days. Imaging studies revealed a well-defined cystic-solid mass with heterogeneous density involving the tail of the pancreas. We performed an en bloc distal pancreatectomy with splenectomy for radical excision, as well as regional lymphadenectomy. The resected specimen revealed a 4.0×5.0 cm exophytic clear-bordered neoplasm of the tail of the pancreas containing necrotic and calcified areas, without splenic invasion. The lymph node involvement was not detected (0/5) and the surgical margins were negative. Microscopy showed pleomorphism with giant cells, spindle-shaped cells with anaplasia, and osteochondroid differentiation. A diagnosis of undifferentiated (spindle cell) carcinoma of the pancreas with focal osteochondroid differentiation was made. The patient declined chemotherapy and extended lymphadenectomy. She suffered from liver and lymph nodes metastasis 9 months after surgery, and she subsequently died 4 months later due to high tumor burden. CONCLUSIONS: Undifferentiated pancreatic carcinoma with osteochondroid differentiation is rare but associated with extremely poor prognosis. It should be included in the differential diagnosis of pancreatic mass lesions.

Radiomics-Based Prediction of Microvascular Invasion Grade in Nodular Hepatocellular Carcinoma Using Contrast-Enhanced Magnetic Resonance Imaging.

Objective: The aim of this study is to develop and verify a magnetic resonance imaging (MRI)-based radiomics model for predicting the microvascular invasion grade (MVI) before surgery in individuals diagnosed with nodular hepatocellular carcinoma (HCC). Methods: A total of 198 patients were included in the study and were randomly stratified into two groups: a training group consisting of 139 patients and a test group comprising 59 patients. The tumor lesion was manually segmented on the largest cross-sectional slice using ITK SNAP, with agreement reached between two radiologists. The selection of radiomics features was carried out using the LASSO (Least Absolute Shrinkage and Selection Operator) algorithm. Radiomics models were then developed through maximum correlation, minimum redundancy, and logistic regression analyses. The performance of the models in predicting MVI grade was assessed using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion matrix. Results: There were no notable statistical differences in sex, age, BMI (body mass index), tumor size, and location between the training and test groups. The AP and PP radiomic model constructed for predicting MVI grade demonstrated an AUC of 0.83 (0.75-0.88) and 0.73 (0.64-0.80) in the training group and an AUC of 0.74 (0.61-0.85) and 0.62 (0.48-0.74) in test group, respectively. The combined model consists of imaging data and clinical data (age and AFP), achieved an AUC of 0.85 (0.78-0.91) and 0.77 (0.64-0.87) in the training and test groups, respectively. Conclusion: A radiomics model utilizing-contrast-enhanced MRI demonstrates strong predictive capability for differentiating MVI grades in individuals with nodular HCC. This model could potentially function as a dependable and resilient tool to support hepatologists and radiologists in their preoperative decision-making processes.

[Relationship between the expression of dual specificity phosphatase-1 and the prognosis of endometrioid adenocarcinoma].

OBJECTIVE: To clarify the relationship between the expression of dual specificity phosphatase-1 (DUSP1) and the prognosis of endometrioid adenocarcinoma. METHODS: The expression of DUSP1 was determined by immunohistochemical staining in specimens from 81 patients with endometrial carcinoma undergoing surgical resection. The relationship between DUSP1 expression, clinicopathological factors and prognosis were further evaluated. RESULTS: In 81 endometrioid carcinoma samples, 59 (72.84%) cases were positive while 22 negative.Except for lymph node metastasis, the expression of DUSP1 was correlated with FIGO stage, tumor grade, myometrial invasion and the expressions of estrogen receptor (ER) and progesterone receptor (PR) (P < 0.05) .Kaplan-Meier analysis showed that patients with a positive DUSP1 expression had significantly prolonged 5-year disease-free survival rates of 98.2% and 76.0% respectively (P < 0.05). And COX regression analysis revealed that the expressions of DUSP1 and PR were independent prognostic indicators of endometrioid carcinoma, the HR (hazard ratio) of DUSP1 negative expression was 21.2.Spearman analysis further showed that the expression of DUSP1 was positively correlated with PR (r = 0.256, P < 0.05). CONCLUSION: DUSP1 may be a potential negative prognostic indicator for endometrioid adenocarcinoma.

A double-cannula pancreatic gastrostomy method for pancreatic duct stenosis due to disconnected pancreatic duct syndrome: A surgical case report.

INTRODUCTION AND IMPORTANCE: Disconnected Pancreatic Duct Syndrome (DPDS) without peripancreatic fluid collections are relatively difficult for endoscopists to manage and usually treated with distal pancreatectomy or pancreaticojejunostomy. However, these procedures are risky for patients with severe edema of pancreatic tissue. We report an original one-stage surgical approach for these patients, namely, the "double-cannula pancreatic gastrostomy method". CASE PRESENTATION: A 38-year-old man was admitted with recurrent acute pancreatitis. ct images suggest pancreatic duct discontinuity syndrome. Intraoperative exploration revealed that pancreas inflammation was severe and distal pancreatectomy or pancreaticojejunostomy were risky. Therefore, we decided to perform a double-cannula pancreatic gastrostomy. A 16F type catheter penetrated the front and back walls of the stomach for gastrostomy, and a 6F catheter was inserted into the pancreatic duct for drainage. We placed the drainage tube of pancreatic duct into the gastrostomy tube to ensure the drainage tube of pancreatic duct could reach the gastric cavity. The gastrostomy tube is led out of the body through the abdominal wall. CLINICAL DISCUSSION: Both endoscopic and surgical approaches have been reported in treating DPDS patients. Internal drainage and excision are common surgical methods. CONCLUSIONS: The double-cannula pancreatic gastrostomy was a safe and effective method in this patient. CORE TIP: In this case, the patient suffered recurrent acute pancreatitis due to disconnected pancreatic duct syndrome. This patient without peripancreatic fluid collections was relatively difficult for endoscopists to manage. However, intraoperative exploration revealed a high risk of distal pancreatectomy or pancreaticojejunostomy. Therefore, we used A double-cannula pancreatic gastrostomy method and successfully treated the complications of pancreatic duct stenosis.

Association of vitamin D and polymorphisms of its receptor with antiviral therapy in pregnant women with hepatitis B.

BACKGROUND: The interruption of mother-to-child transmission (MTCT) is considered important to decrease the individual and population morbidity of hepatitis B virus (HBV) infection as well as the global burden of hepatitis B. Serum vitamin D (VD) is associated with hepatitis B. AIM: To assess whether baseline VD levels and single nucleotide polymorphisms of the VD receptor gene (VDR SNPs) are associated with the efficacy of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT in pregnant women with high HBV viral loads. METHODS: Thirty-eight pregnant women who were at high risk for MTCT of HBV (those with an HBV DNA level ≥ 2 × 105 IU/mL during 12-24 wk of gestation) receiving antiviral therapy of TDF between June 1, 2019 and June 30, 2021 in Mianyang were included in this retrospective study. The women received 300 mg TDF once daily from gestational weeks 24-28 until 3 mo after delivery. To further characterize the clinical relevance of maternal serum HBV DNA levels, we stratified patients according to HBV DNA level as follows: Those with levels < 2 × 105 (full responder group) vs those levels ≥ 2 × 105 IU/mL (partial responder group) at delivery. Serum levels of 25-hydroxyvitamin D [25(OH)D], liver function markers, virological parameters, VDR SNPs and other clinical parameters were collected to analyze their association with the efficacy of TDF. The Mann-Whitney U test or t test was used to analyze the serum levels of 25(OH)D in different groups. Multiple linear regressions were utilized to analyze the determinants of the maternal HBV DNA level at delivery. Univariate and multivariate logistic regression analyses were employed to explore the association of targeted antiviral effects with various characteristics at baseline and delivery. RESULTS: A total of 38 pregnant women in Mianyang City at high risk for MTCT of HBV were enrolled in the study. The MTCT rate was 0%. No mother achieved hepatitis B e antigen or hepatitis B surface antigen (HBsAg) clearance at delivery. Twenty-three (60.5%) participants were full responders, and 15 (39.5%) participants were partial responders according to antiviral efficacy. The present study showed that a high percentage (76.3%) of pregnant women with high HBV viral loads had deficient (< 20 ng/mL) or insufficient (≥ 20 but < 31 ng/mL) VD levels. Serum 25(OH)D levels in partial responders appeared to be significantly lower than those in full responders both at baseline (25.44 ± 9.42 vs 17.66 ± 5.34 ng/mL, P = 0.006) and delivery (26.76 ± 8.59 vs 21.24 ± 6.88 ng/mL, P = 0.044). Serum 25(OH)D levels were negatively correlated with maternal HBV DNA levels [log(10) IU/mL] at delivery after TDF therapy (r = -0.345, P = 0.034). In a multiple linear regression analysis, maternal HBV DNA levels were associated with baseline maternal serum 25(OH)D levels (P < 0.0001, ß = -0.446), BMI (P = 0.03, ß = -0.245), baseline maternal log10 HBsAg levels (P = 0.05, ß = 0.285) and cholesterol levels at delivery (P = 0.015, ß = 0.341). Multivariate logistic regression analysis showed that baseline serum 25(OH)D levels (OR = 1.23, 95%CI: 1.04-1.44), maternal VDR Cdx2 TT (OR = 0.09, 95%CI: 0.01-0.88) and cholesterol levels at delivery (OR = 0.39, 95%CI: 0.17-0.87) were associated with targeted antiviral effects (maternal HBV DNA levels < 2 × 105 at delivery). CONCLUSION: Maternal VD levels and VDR SNPs may be associated with the efficacy of antiviral therapy in pregnant women with high HBV viral loads. Future studies to evaluate the therapeutic value of VD and its analogs in reducing the MTCT of HBV may be justified.

The differential effects of sarcopenia and cachexia on overall survival for pancreatic ductal adenocarcinoma patients following pancreatectomy: A retrospective study based on a large population.

OBJECTIVES: Both cachexia and sarcopenia have been considered adverse predictors for prognosis in patients with pancreatic cancer; although sarcopenia and cachexia share some similarities, they are still defined as distinct nutritional conditions. We aimed to explore the differential impacts of sarcopenia and cachexia on prognosis for pancreatic ductal adenocarcinoma (PDAC) patients following radical excision. METHODS: From January 2015 to May 2022, 614 patients undergoing surgery for PDAC were retrospectively included. Sarcopenia was defined as the L3 total skeletal muscle index below 52.4 cm2 /m2 (men) and 38.5 cm2 /m2 (women). Cachexia was classified according to the following criteria: involuntary weight loss >5% over the past 6 months, or weight loss >2% and BMI <20 kg/m2 , or weight loss >2% and sarcopenia. RESULTS: Of the 614 patients included in the analysis, 62% and 48% were diagnosed with sarcopenia and cachexia, respectively. Kaplan-Meier analysis showed that sarcopenia and/or cachexia were significantly associated with worse overall survival (OS) rather than worse recurrence-free survival (RFS). Moreover, Cox regression analysis revealed that cachexia rather than sarcopenia was an adverse factor for OS in all PDAC patients. For poorly differentiated PDAC, both cachexia and sarcopenia were significantly associated with shorter OS. However, for moderately/well-differentiated PADC, cachexia was an independent factor for adverse OS, but not sarcopenia. CONCLUSIONS: Sarcopenia and cachexia have different effects on OS for PDAC patients undergoing radical excision. This difference may provide some important information for preoperative management.

Regional differences in islet amyloid deposition in the residual pancreas with new-onset diabetes secondary to pancreatic ductal adenocarcinoma.

BACKGROUND: Islet amyloid deposition and reduced ß-cell mass are pathological hallmarks in type 2 diabetes mellitus subjects. To date, the pathological features of the islets in diabetes secondary to pancreatic ductal adenocarcinoma (PDAC) have not been specifically addressed. AIM: To provide further insight into the relationship between islet amyloid deposition of the residual pancreas in PDAC patients and to explore whether regional differences (proximal vs distal residual pancreas) are associated with islet amyloid deposition. METHODS: We retrospectively collected clinical information and pancreatic tissue removed from tumors of 45 PDAC patients, including 14 patients with normal glucose tolerance (NGT), 16 patients with prediabetes and 15 new-onset diabetes (NOD) patients diagnosed before surgery by an oral glucose tolerance test at West China Hospital from July 2017 to June 2020. Pancreatic volume was calculated by multiplying the estimated area of pancreatic tissue on each image slice by the interval between slices based on abdominal computer tomography scans. Several sections of paraffin-embedded pancreas specimens from both the proximal and/or distal regions remote from the tumor were stained as follows: (1) Hematoxylin and eosin for general histological appearance; (2) hematoxylin and insulin for the determination of fractional ß-cell area (immunohistochemistry); and (3) quadruple insulin, glucagon, thioflavin T and DAPI staining for the determination of ß-cell area, α-cell area and amyloid deposits. RESULTS: Screening for pancreatic histologic features revealed that duct obstruction with islet amyloid deposition, fibrosis and marked acinar atrophy were robust in the distal pancreatic regions but much less robust in the proximal regions, especially in the prediabetes and NOD groups. Consistent with this finding, the remnant pancreatic volume was markedly decreased in the NOD group by nearly one-half compared with that in the NGT group (37.35 ± 12.16 cm3 vs 69.79 ± 18.17 cm3, P < 0.001). As expected, islets that stained positive for amyloid (islet amyloid density) were found in the majority of PDAC cases. The proportion of amyloid/islet area (severity of amyloid deposition) was significantly higher in both prediabetes and NOD patients than in NGT patients (P = 0.002; P < 0.0001, respectively). We further examined the regional differences in islet amyloid deposits. Islet amyloid deposit density was robustly increased by approximately 8-fold in the distal regions compared with that in the proximal regions in the prediabetes and NOD groups (3.98% ± 3.39% vs 0.50% ± 0.72%, P = 0.01; 12.03% vs 1.51%, P = 0.001, respectively). CONCLUSION: In conclusion, these findings suggest that robust alterations of the distal pancreas due to tumors can disturb islet function and structure with islet amyloid formation, which may be associated with the pathogenesis of NOD secondary to PDAC.

TSPO is a novel biomarker for prognosis that regulates cell proliferation through influencing mitochondrial functions in HCC.

The disorder of mitochondrial functions plays a key role in oncogenesis. It is known that TSPO (18-kDa translocator protein) lies in a peculiar location at the interface between the mitochondria and the cytosol. TSPO is found in many types of tissues and is associated with multiple cellular processes, including apoptosis, cell proliferation and the regulation of mitochondria. However, the involvement of TSPO in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that TSPO is upregulated in HCC tissue and is associated with poor differentiation and poor survival. Multivariate analyses showed that TSPO was an independent predictive factor for poor prognosis in HCC patients. For the first time, we provided evidence that TSPO knockdown suppressed HCC cell proliferation in vitro. Hence, TSPO knockdown-induced apoptosis by disturbing mitochondrial function by enhancing the formation of reactive oxygen species (ROS) and decreasing the mitochondrial membrane potential (ΔΨm). An assay exploring the underlying mechanism revealed that TSPO knockdown modulated apoptotic regulatory proteins by regulating the ERK signaling pathway. Through a functional assay and an in vivo mouse model, the anti-cancer effect of PK11195, a specific ligand of TSPO, on HCC was revealed. In summary, TSPO may potentially serve as a prognostic biomarker, and TSPO might be a potential therapeutic target for HCC.

Nitric oxide and ATP-sensitive potassium channels mediate lipopolysaccharide-induced depression of central respiratory-like activity in brain slices.

Infection may result in early abnormalities in respiratory movement, and the mechanism may involve central and peripheral factors. Peripheral mechanisms include lung injury and alterations in electrolytes and body temperature, but the central mechanisms remain unclear. In the present study, brainstem slices harvested from rats were stimulated with lipopolysaccharide at different doses. Central respiratory activities as demonstrated by electrophysiological activity of the hypoglossal rootlets were examined and the mechanisms were investigated by inhibiting nitric oxide synthase and ATP-sensitive potassium channels. As a result, 0.5 µg/ml lipopolysaccharide mainly caused inhibitory responses in both the frequency and the output intensity, while 5 µg/ml lipopolysaccharide caused an early frequency increase followed by delayed decreases in both the frequency and the output intensity. At both concentrations the inhibitory responses were fully reversed by inhibition of nitric oxide synthase with Nω-nitro-L-arginine methyl ester hydrochloride (20 µM), and by inhibition of ATP- sensitive potassium channels with glybenclamide (100 µM). These results show that direct lipopolysaccharide challenge altered central respiratory activity in dose- and time- related manners. Nitric oxide synthase and ATP-sensitive potassium channels may be involved in the respiratory changes.

Effect of recombinant human growth hormone and interferon gamma on hepatic collagen synthesis and proliferation of hepatic stellate cells in cirrhotic rats.

BACKGROUND: Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model. METHODS: Cirrhosis was induced in rats using carbon tetrachloride. Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone. The control group was given saline. The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis. Activated hepatic stellate cells were prepared from cirrhotic rats. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro. RESULTS: Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration. In vitro, recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner (10(-3)-10(-1) mg/100 µL), and interferon gamma (10(-2)-10(-1) µg/100 µL) significantly inhibited their growth compared to the control group. Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner (10(-1) µg/100 µL, P<0.05, 10(-2)-10(-3) µg/100 µL, P>0.05) and a time-dependent manner (P<0.05). CONCLUSIONS: Recombinant human growth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro. It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.

Treatment and five-year follow-up of type A insulin resistance syndrome: A case report.

BACKGROUND: Type A insulin resistance syndrome (TAIRS) is a rare disorder characterized by severe insulin resistance due to defects in insulin receptor signaling. No specific drugs are available for the treatment of TAIRS. We report a case of TAIRS successfully treated with pioglitazone and flutamide for 5 years. CASE SUMMARY: We present the rare case of a female patient aged 11 years and 9 mo with type A insulin resistance and an INSR heterozygous mutation (c.3614C>T), who was treated with a combination of pioglitazone and flutamide. This treatment regimen reduced hemoglobin A1c, fasting insulin and androgen levels. CONCLUSION: Pioglitazone attenuated insulin resistance in this patient with TAIRS, and flutamide ameliorated masculinization.

Prospects and applications of enucleation in solid pseudopapillary neoplasms of the pancreas.

Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare, low-grade, malignant neoplasms that are mostly seen in young women in the second and third decades of life and are quite uncommon in children. Standard resection for benign and borderline neoplasms of the pancreas is associated with a substantial risk of postoperative morbidity and long-term functional impairment, whereas enucleation leads to less morbidity and preserves healthy parenchyma as well as exocrine and endocrine function. Enucleation of SPNs has been increasingly reported to be feasible and safe for preserving the normal physiological function of the pancreas, especially in teenagers and children. This review summarizes findings published in recent years on the enucleation of SPNs as well as potential future developments and directions. Enucleation has undoubtedly come to stay as an alternative surgical procedure for SPNs. However, many questions remain unresolved, and future directions toward the best surgical indication, the prevention and intervention of complications, especially pancreatic fistula, intraoperative resection margin safety assessment, and long-term oncology prognosis remain to be evaluated and should be explored in future clinical trials.

[Mechanism of Lead-zinc Enrichment and Resistance of Spent Mushroom Compost to Lead-Zinc Slag in Koelreuteria paniculata].

Phytoremediation is an ecological technique for tailing area restoration; adding substrate modifiers can reduce the stress of heavy metals on plants and enhance the restoration efficiency. The woody plant Koelreuteria paniculata was used as a test plant and potted in 100% tailings (S), 90% tailings+5% mushroom residue (SMC)+5% CaCO3 (MS), and natural red soil (RS). The effects of physiological responses and tolerance enrichment effects on Pb and Zn tolerance in K. paniculata under different treatments were investigated to compare the growth morphology, microscopic morphological changes, and microbial diversity changes in each substrate of K. paniculata seedlings. The results showed that compared with the control group S, the MS treatment group could significantly improve the structure and fertility of the tailing substrates; significantly enhance the relevant physiological indicators such as biomass, plant height, and chlorophyll content of K. paniculate; and increase the accumulated heavy metal content in K. paniculata. In the treatment group, the overall physiological indexes of MS compared to RS biomass and plant height were promoted, and the total root length increased up to 69.3%, whereas the average root diameter of RS in the treatment group decreased 118.7% compared to that in the control group S. The MS treatment group showed a 266.67% increase in Pb and Zn residue state, a significant decrease in the weak acid extractable state and oxide-bound state compared to that in the control group S. The heavy metals were less active for plant migration. Furthermore, most of the heavy metals were trapped in the roots of K. paniculata, and the changes in its root conformation indicated its strong adaptability in the face of high Pb stress. Transmission electron microscopy (TEM) analysis showed that the higher concentration of heavy metals in the S control damaged the cell wall structure and caused toxic effects on plant cells. The addition of the modifier effectively alleviated the effects of heavy metal stress on various tissues of K. paniculata, affected the structure of microbial communities, significantly increased microbial richness and diversity, and enhanced the adaptability of K. paniculata to heavy metals and phytoremediation ability.