Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Objective:To investigate the diagnostic value of dynamic contrast enhanced MRI (DCE-MRI) quantitative parameters for preoperative staging of gastric cancer and its relationship with prognostic factors.Methods:The clinical data of 98 patients with gastric cancer from March 2021 to March 2022 in Guangyuan First People′s Hospital were retrospectively analyzed. All patients underwent DCE-MRI examination, MRI features were observed, and the DCE-MRI quantitative parameters were recorded, including the transport constant (K trans), volume fraction (V e) and rate constant (K ep). The expression levels of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) in gastric cancer tissue were detected by immunohistochemistry methods. The correlation between DCE-MRI quantitative parameters and T stage, HER2, EGFR of gastric cancer was analyzed by Spearman method; the receiver operating characteristic (ROC) curve was used to evaluate the diagnosis value of DCE-MRI quantitative parameters in T staging of gastric cancer. Results:Among 98 patients with gastric cancer, T 1 to T 2 staging was in 50 cases, T 3 to T 4 staging was in 48 cases; HER2 positive expression in gastric cancer tissue was in 35 cases, negative expression was in 63 cases; EGFR positive expression in gastric cancer tissue was in 43 cases, negative expression was in 55 cases. The K trans and V e in patients with T 3 to T 4 staging were significantly higher than those in patients with T 1 to T 2 staging: (0.25 ± 0.04) min -1 vs. (0.19 ± 0.03) min -1 and 0.45 ± 0.11 vs. 0.39 ± 0.09, and there were statistical differences ( P<0.01); there was no statistical difference in K ep between the two ( P>0.05). The K trans and V e in patients with HER2 positive expression were significantly higher than those in patients with HER2 negative expression: (0.27 ± 0.06) min -1 vs. (0.19 ± 0.03) min -1 and 0.49 ± 0.13 vs. 0.38 ± 0.08, and there were statistical differences ( P<0.01); there was no statistical difference in K ep between the two ( P>0.05). The K trans and V e in patients with EGFR positive expression were significantly higher than those in patients with EGFR negative expression: (0.28 ± 0.07) min -1 vs. (0.17 ± 0.04) min -1 and 0.50 ± 0.14 vs. 0.36 ± 0.08, and there were statistical differences ( P<0.01); there was no statistical difference in K ep between the two ( P>0.05). Spearman analysis result showed that the K trans was positively correlated with gastric cancer T stage, and the expression of HER2, EGFR in gastric cancer tissue ( r = 0.539, 0.612 and 0.640; P<0.01), the V e was positively correlated with gastric cancer T stage, and the expression of HER2, EGFR in gastric cancer tissue ( r = 0.462, 0.551 and 0.583; P<0.01), while there was no correlated between K ep and gastric cancer T stage and the expression of HER2, EGFR in gastric cancer tissue ( P>0.05). ROC curve analysis result showed that the area under the curve of K trans combined with V e in diagnosis the T 3 to T 4 staging of gastric cancer was 0.929, with a specificity of 81.25% and a specificity of 92.00%. Conclusions:The DCE-MRI quantitative parameters K trans and V e have certain value in the diagnosis of gastric cancer T staging, and they are closely related to the expression of prognostic factors HER2 and EGFR.

Nonalcoholic fatty liver disease (NAFLD) occurrence and progression are associated with lipid accumulation, insulin resistance, inflammation, liver damage, fibrosis, and other factors. AMP-dependent protein kinase (AMPK) is a key molecule that regulates bioenergy metabolism and participates in multiple biological processes, including lipid metabolism, autophagy, inflammation, and cell apoptosis. Promoting AMPK activation can reduce hepatic lipid accumulation and insulin resistance, alleviate the development of NAFLD, reduce liver inflammation and fibrosis, and inhibit the progression of NAFLD to nonalcoholic steatohepatitis.

Mitochondrial dysfunction is closely related to the occurrence and development of benign and malignant diseases of the pancreas. Mitochondrial membrane of the respiratory chain electron transfer and energy transfer plays an important role in maintaining normal cellular function. When the respiratory chain was disrupted, the oxidative stress was increased in the cell, and produced a large number of oxide intermediate products which target mitochondrial protein, DNA, etc, lead to mitochondrial dysfunction finally induced acute pancreatitis, pancreatic cancer and other diseases. In addition, mitochondrial homeostasis plays an indispensable role in maintaining the normal function of islet cells. This paper reviewed the research status of mitochondrial dysfunction in pancreatic diseases.

ObjectiveTo investigate the protective effect of tanshinone I (T-I) on hepatic ischemia-reperfusion injury (HIRI) in mice. MethodsA total of 36 C57BL/6J mice were randomly divided into sham-operation group, ischemia-reperfusion (IR) group, IR+T-I (5 mg/kg) group, IR+T-I (10 mg/kg) group, IR+T-I (20 mg/kg) group, and IR+T-I (40 mg/kg) group, with 6 mice in each group. Each group was given intraperitoneal injection. The mice in the sham-operation group and the IR group were injected with an equal volume of the solvent olive oil; the mice in the IR+T-I groups were administered once a day for 7 consecutive days, a model of 70% HIRI was established at 2 hours after the last administration, and serum and liver samples were collected after 6 hours of reperfusion. Related kits were used to measure the serum level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the content of superoxide dismutase (SOD), malondialdehyde (MDA), caspase-3, and reduced glutathione (GSH) in liver tissue; HE staining was used to observe liver histopathology; the TUNEL method was used to measure the level of hepatocyte apoptosis; immunohistochemistry was used to measure the protein expression of caspase-3 and heme oxygenase-1 (HO-1). A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the IR group, the IR+T-I (20mg/kg) group had significant reductions in the serum levels of ALT (192.48±23.67 U/L vs 336.90±41.52 U/L, P＜0.01) and AST (123.19±9.16 U/L vs 206.90±18.81 U/L, P＜0.01), and thus 20 mg/kg was determined as the optimal concentration. Compared with the IR group, the IR+T-I (20 mg/kg) group had significant reductions in MDA (1.34±0.21 μmol/mg vs 3.48±0.95 μmol/mg, P＜0.05) and caspase-3 (0.69±0.97 μmol/mg vs 1.04±0.35 μmol/mg, P＜0.05) and significant increases in SOD (274.47±30.53 U/mg vs 160.29±27.37 U/mg, P＜0.05) and GSH (2.12±0.27 μmol/mg vs 1.03±0.42 μmol/mg, P＜0.05). HE staining showed that the IR group had disordered structure of hepatic lobules and focal or extensive degeneration and necrosis of hepatocytes; compared with the IR group, the IR+T-I (20 mg/kg) group had a reduction in the area of hepatocyte necrosis and a basically complete structure of the liver. Immunohistochemistry showed that compared with the IR group, the IR+T-I (20 mg/kg) group had significant reductions in the number of apoptotic hepatocytes and the protein expression of caspase-3 and a significant increase in the protein expression of HO-1. ConclusionT-I exerts a protective effect against HIRI in mice by inhibiting liver oxidative stress response and hepatocyte apoptosis.

Non-alcoholic steatohepatitis (NASH) is an important link for the progression of metabolic-related fatty liver disease to end-stage liver disease such as cirrhosis and hepatocellular carcinoma, which seriously endangers human health. NASH pathogenesis is complex, and involves the interaction between hepatic parenchymal and non-parenchymal cells (NPCs), sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and so on. Herein, the relevant research progress of NPCs in the pathogenesis of NASH is reviewed in order to further understand the role of NPCs in NASH.

Objective:To investigate the correlations of dynamic iodine nutrition status and thyroid function in pregnant women and newborns in Lingang of Shanghai, so as to provide an evidence for whether urine iodine testing and iodine supplementation should be carried out.Methods:A prospective study was conducted by randomly selecting pregnant women from October 2017 to October 2018 in Shanghai Sixth People’s Hospital East Affiliated to Shanghai University of Medicine & Health Sciences. The pregnant women were divided into early (5-12 weeks), middle (22-24 weeks), late pregnancy (36-37 weeks). Samples of serum and 24 hours urine were collected to test on thyrotropin (TSH), free thyroxine (FT 4), free triiodothyronine (FT 3), anti-thyroid peroxidase (TPOAb), anti-thyroglobulin (TgAb) and urinary iodine. TSH in neonatal heel blood was analyzed 72 h after birth (newborns from pregnant women in the late pregnancy). The differences of thyroid function of pregnant women with different pregnant periods and different urinary iodine levels were analyzed, as well as the neonatal TSH levels of pregnant women with different urinary iodine levels. Results:A total of 109, 90 and 54 cases of pregnant women in early, middle and late pregnancy were investigated and the medians of urinary iodine were 120.95, 136.30 and 116.80 μg/L, respectively. There was no significant difference in urinary iodine content among different pregnant periods( P > 0.05). The proportions of urinary iodine level less than 150 μg/L in early, middle and late pregnancy were 75.2% (82/109), 61.1% (55/90) and 59.3% (32/54), respectively. The median values of serum TSH in early, middle and late pregnancy were 1.81, 1.95 and 2.29 mU/L, mean values of FT 3 were (5.21 ± 0.84), (4.79 ± 0.72) and (4.13 ± 0.56)pmol/L, and means of FT 4 were (16.48 ± 2.58), (15.02 ± 2.78) and (13.31 ± 1.87) pmol/L, respectively. The FT 3 and FT 4 levels in the late pregnancy were lower than those in the early and middle pregnancy, while the TSH levels in the late pregnancy were higher than those in the early and middle pregnancy. There were no significant difference in serum FT 3, FT 4 and TSH levels among early, middle and late pregnancy under different urinary iodine levels. The median TSH of newborn heel blood was 1.48 mU/L. There was no statistically significant difference between the neonatal heel blood TSH level of pregnant women with urinary iodine < 150 μg/L [1.45(1.09, 2.23)mU/L] in late pregnancy and those with urinary iodine ≥150 μg/L [1.42 (1.14, 2.61) mU/L, Z=- 0.354, P > 0.05]. Conclusions:There is mild iodine deficiency in pregnant women in Lingang of Shanghai. However, due to the compensatory regulation, it has no significant effect on the thyroid function of mother and newborn. Monitoring of iodine nutrition of pregnant women should be carried out and iodine supplementation should be done scientifically and reasonably.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

OBJECTIVETo observe the clinical efficacy differences between different needling methods for dry eye syndrome.

METHODSSixty patients of dry eye syndrome were randomly divided into an observation group and a control group, 30 cases (60 eyes) in each group. Shangjingming (Extra), Xiajingming (Extra), Tongziliao (GB 1), Cuanzhu (BL 2), Fengchi (GB 20), Hegu (LI 4), Sanyinjiao (SP 6), Taixi (KI 3) and Taichong (LR 3) were selected in the two groups. The control group was treated with conventional acupuncture, while the observation group was treated with guiding-acupuncture. Electroacupuncture (EA) was used at bilateral Tongziliao (GB1) and Cuanzhu (BL 2), 30 min per treatment. The treatment was given three times per week. Totally 1-month treatment (12 treatments) was given. The eye symptom score, breakup time of tear film (BUT), Schirmer Ⅰ test (SⅠT) and visual analogue scale (VAS) score were compared before and after treatment in the two groups. The clinical efficacy was compared between the two groups.

RESULTSCompared before treatment, the eye symptom score, BUT, SⅠT and VAS score were improved after treatment in the two groups (all<0.001); the improvements of eye symptom score and SⅠT in the observation group were superior to those in the control group (both<0.05). The differences of BUT and VSA score between the two groups were not significant (both>0.05). The total effective rate was 86.7% (52/60) in the observation group, which was superior to 73.3% (44/60) in the control group (<0.05). .

CONCLUSIONThe conventional EA and guiding-acupuncture combined with EA are both effective for dry eye syndrome, and the efficacy of guiding-acupuncture combined with EA is superior to that of conventional EA.

Objective To analyze the laboratory determination results of hand-foot-mouth disease(HFMD)and explore its sig-nificance.Methods Pharyngeal swab specimens were collected from 502 children with HFMD(severe case:104 cases and mild case:398 cases).Specific RNA of enterovirus primer(EV),enterovirus71 (EV71)and coxsackievirus A16(CA16)were detected by real-time fluorescence polymerase chain reaction(RT-PCR).Simultaneously,white blood cell (WBC),direct bilirubin(DBIL),alanine transarninase(ALT),creatine kinase MB isoenzyme(CK-MB)and lactic dehydrogenase (LDH )were determined,and the results were analyzed.Results Among the 502 children,384 cases were positive for EV,262 cases were positive for EV71,and 39 cases were positive for CA16.The positive rates were 76.49%,52.19% and 7.76%,respectively.In the 104 HFMD severe cases,EV71 positive rate was 92.31%(96/104).There were clearly more boys than girls.The age distribution was mainly in the group under 3-year-old(402 cases,80.08%).In the group under 3-year-old,there were 97 severe cases(93.27%),and the EV71 positive rate was 92.78%(90/97).Serum levels of WBC,DBIL,ALT,CK-MB and LDH were higher in severe HFMD group than in mild group(P <0.05).Conclusion The HFMD occurred mostly at the children under 3-year-old.The HFMD appeared is mainly related to the EV infection,and EV71 is the main pathogen causing the severe cases of HFMD.