Current situation and future countermeasures of mobile internet remote teaching of pediatric imaging / 中华医学教育探索杂志

Due to the limitations professional status and training channels, the training of pediatric imaging talents in China is seriously insufficient. Pediatric imaging doctors are concentrated in children's hospitals. Pediatric imaging knowledge and talents in primary medical institutions are scarce, which is not conducive to the construction of hierarchical diagnosis and treatment system. Large-scale telemedicine and online medical treatment based on mobile Internet have become the mainstream platforms for medical consultation and teaching, providing a good opportunity for remote teaching of pediatric imaging, and are expected to become a powerful tool for training pediatric imaging talents. The analysis of literature, mobile phone application market software and cost-effectiveness shows that the current large-scale telemedicine construction cycle is long, the construction and maintenance costs are high, and it is vulnerable to geographical and environmental constraints. It is still a long way to go for remote teaching in hospitals below the county level. The use of mobile terminals and mobile Internet is very convenient. It is an excellent choice to realize the remote teaching of pediatric imaging. It is expected to solve the problem of pediatric imaging talent training and skill dissemination.

Effects of tetramethylpyrazine on the expressions of ferroptosis related molecules after spinal cord injury in rats / 国际中医中药杂志

Objective:To study the effects of tetramethylpyrazine on the expressions of ferroptosis related molecules after spinal cord injury; To explore the mechanism of tetramethylpyrazine promoting the repair of spinal cord injury (SCI).Methods:Totally 36 SD rats were divided into sham-operation group, model group and tetramethylpyrazine group according to random number table method, with 12 rats in each group. The rats in the sham-operation group underwent laminectomy without injury to the spinal cord. The SCI model was prepared in the other two groups. The rats in the tetramethylpyrazine group were intraperitoneally injected with tetramethylpyrazine of 80 mg/kg, and the rats in the sham-operation group and model group were intraperitoneally injected with the same volume of normal saline, once a day, continuous intervention for 28 days. One day before operation and 1, 3, 5, 7, 14, 21, 28 days after operation, BBB limb motor function score was used to evaluate the limb motor function of rats. Nissl staining was used to observe the morphology of neurons. Prussian staining was used to observe iron deposition. Assay kit was used to detect the contents of MDA and ROS in spinal cord tissue. Western blot was used to detect the protein expressions of xCT, GPX4 and ACSL4, and qPCR was used to detect the mRNA expressions of mRNA of xCT, GPX4 and ACSL4.Results:On the 14th, 21st and 28th days after operation, compared with the model group, the BBB score of tetramethylpyrazine group increased ( P<0.01); tetramethylpyrazine could significantly improve the morphology and structure of neurons and reduce the iron content in spinal cord tissue; compared with the model group, the contents of MDA and ROS in the spinal cord tissue of tetramethylpyrazine group decreased ( P<0.01); the levels of xCT and GPX4 mRNA and protein increased ( P<0.01), while the expression of ACSL4 mRNA and protein decreased ( P<0.01). Conclusion:Tetramethylpyrazine can regulate lipid peroxidation by regulating the expressions of ferroptosis related molecules, which is conducive to the recovery of limb motor function in rats with spinal cord injury.

Relationship between nutrient-related dietary pattern and mild cognitive impairment in middle-aged and elderly people in 15 provinces of China / 中华流行病学杂志

Objective: To explore the relationship between nutrient-related dietary pattern and mild cognitive impairment (MCI) in middle-aged and elderly people. Methods: A total of 6 444 middle-aged and elderly people aged ≥55 years were selected in 2018 China Health and Nutrition Survey. MCI was evaluated by Mini-Mental State Examination, and the intakes of various foods were obtained by consecutive 3-day 24-hour dietary survey and weighing method. The intakes of various nutrients and total dietary energy were calculated based on the food composition table. Demographic and social information, lifestyle and health status of the respondents were obtained through questionnaire survey and physical measurements. In this study, vitamin C, vitamin E, zinc, iron, copper and selenium were selected as dependent variables. Nutrient-related dietary patterns were extracted by reduced rank regression method, and the relationship between dietary patterns and MCI was analyzed by multivariate logistic regression model. Results: Six dietary patterns were extracted in this study, and dietary pattern 1 with the highest explanatory degree was selected for subsequent analysis. Dietary pattern 1 was characterized by higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products and plant oil. Multivariate logistic regression analysis showed that the risk of MCI was lower in Q4 dietary score group than in Q1 dietary score group (OR=0.69, 95%CI: 0.49-0.98) in the 55-64 age group. In people with sleep duration of 8 hours per day, the risk of MCI was reduced in Q2, Q3 and Q4 dietary score groups compared with the Q1 dietary score group, with OR values of 0.68 (95%CI: 0.51-0.92), 0.67 (95%CI: 0.49-0.92) and 0.65 (95%CI: 0.45-0.92), respectively. Interaction analysis showed that the risk for MCI increased in those aged 65-74 years and ≥75 years compared with those aged 55-64 years in Q1 dietary score group. However, the risk for MCI decreased in both age groups as dietary pattern scores increased. Compared with those with sleep duration less or more than 8 hours per day in Q1 dietary score group, those with sleep duration of 8 hours per day in Q2 and Q3 dietary score groups had a reduced risk for MCI. Conclusion: Dietary patterns with higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products, and plant oil are negatively associated with MCI in people aged 55-64 years and those who slept 8 hours per day, and may reduce the risk of MCI with aging.

Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia / 中国当代儿科杂志

OBJECTIVES@#To study the safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia (R/R-ALL).@*METHODS@#Six children with R/R-ALL who received blinatumomab treatment from August 2021 to August 2022 were included as subjects, and a retrospective analysis was performed for their clinical data.@*RESULTS@#Among the six children, there were three boys and three girls, with a median age of 10.5 (5.0-13.0) years at the time of inclusion. Of all six children, one had refractory ALL and did not achieve remission after several times of chemotherapy, and 5 relapsed for the first time, with a median time of 30 (9-60) months from diagnosis to relapse. Minimal residual disease (MRD) before treatment was 15.50% (0.08%-78.30%). Three children achieved complete remission after treatment, among whom two had negative conversion of MRD. Five children had cytokine release syndrome (CRS), among whom 3 had grade 1 CRS and 2 had grade 2 CRS. Four children were bridged to allogeneic hematopoietic stem cell transplantation, with a median interval of 50 (40-70) days from blinatumomab treatment to transplantation. The six children were followed up for a median time of 170 days, and the results showed an overall survival rate of 41.7% (95%CI: 5.6%-76.7%) and a median survival time of 126 (95%CI: 53-199) days.@*CONCLUSIONS@#Blinatumomab has good short-term safety and effectiveness in the treatment of childhood R/R-ALL, and its long-term effectiveness needs to be confirmed by studies with a larger sample size.

Optimized treatment of childhood B-lineage acute lymphoblastic leukemia / 中国当代儿科杂志

Childhood acute lymphoblastic leukemia (ALL) accounts for about 75% of childhood leukemia cases, and B-lineage acute lymphoblastic leukemia (B-ALL) accounts for more than 80% of childhood ALL cases. Over the past half century, new molecular biological targets discovered by new techniques have been used in precise stratification of disease prognosis, and there has been a gradual increase in the 5-year overall survival rate of childhood ALL. With the increasing attention to long-term quality of life, the treatment of childhood B-ALL has been constantly optimized from induction therapy to the intensity of maintenance therapy, including the treatment of extramedullary leukemia without radiotherapy, which has been tried with successful results. The realization of optimized treatment also benefits from the development of new techniques associated with immunology and molecular biology and the establishment of standardized clinical cohorts and corresponding biobanks. This article summarizes the relevant research on the implementation of precise stratification and the intensity reduction and optimization treatment of B-ALL in recent years, providing reference for clinicians.

Bioequivalence study of cinacalcet hydrochloride tablets in healthy Chinese volunteers / 中国临床药理学与治疗学

AIM: To evaluate the bioequivalence of cinacalcet hydrochloride tablets in healthy Chinese volunteers. METHODS: A randomized, open, double-period and crossover trial was conducted, 48 healthy volunteers were administered a single dose of cinacalcet test tablets or reference tablets orally under each fasting and fed condition. The concentration of cinacalcet was determined by validated LC-MS/MS method. Pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 to study its bioequivalence. RESULTS: The main pharmacokinetic parameters of test tablets and reference tablets under fasting condition were as follows: C

Regulation of Yes associated protein in diabetic nephropathy mice by Yishen Huashi Granule / 中国药理学通报

Aim To explore the protective effect of Yishen Huashi Granule (YSHS) on streptozotocin (STZ) - indueed diabetes nephropathy (DN) in mice and its possible mechanism. Methods The STZ induced DN mice model was established, which was randomly divided into model group, YSHS group and YAP inhibitor Vertepofin group, and the eontrol group was also established. The intervention was started eight weeks after the successful modeling with the course of four weeks. Urine protein concentration before and after intervention in each group as well as serum creatinine (Scr) and blood urea nitrogen (Bun) levels after intervention were measured. After the treatment, the mice were sacrificed, and the pathological changes of glomeruli were observed by light microscope HE staining. The protein expression of YAP, p-YAP S127 and CTGF were detected by Western blot, and the mRNA expressions of YAP, CTGF and podocyte functional proteins nephrin, podophyxin and WT1 were detected by RT-PCR. Results The biochemical indexes of YSHS group were better than those of model group, and HE staining showed that the pathological injury of glomeruli was improved. In the model group the protein expression of YAP, p-YAP (S127) and CTGF as well as the mRNA expression of YAP and CTGF increased, while the mRNA expression of nephrin, podocalyxin and WT1 decreased. After YSHS treatment, the protein expression of YAP, p-YAP S127, CTGF and the mRNA expression of YAP and CTGF decreased, while the mRNA expression of nephrin, podocalyxin and WT1 increased. Conclusions YSHS can reduce urinary protein, protect renal function and alleviate glomerular pathological injury in DN mice. Its possible mechanism may be related to the down-regulation of YAP in renal tissue, the reduction of CTGF expression level and the up-regulation of podocyte protein mRNA expression.

Clinical features and prognosis of juvenile myelomonocytic leukemia: an analysis of 63 cases / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical features of juvenile myelomonocytic leukemia (JMML) and their association with prognosis.@*METHODS@#Clinical and prognosis data were collected from the children with JMML who were admitted from January 2008 to December 2016, and the influencing factors for prognosis were analyzed.@*RESULTS@#A total of 63 children with JMML were included, with a median age of onset of 25 months and a male/female ratio of 3.2∶1. JMML genetic testing was performed for 54 children, and PTPN11 mutation was the most common mutation and was observed in 23 children (43%), among whom 19 had PTPN11 mutation alone and 4 had compound PTPN11 mutation, followed by NRAS mutation observed in 14 children (26%), among whom 12 had NRAS mutation alone and 2 had compound NRAS mutation. The 5-year overall survival (OS) rate was only 22%±10% in these children with JMML. Of the 63 children, 13 (21%) underwent hematopoietic stem cell transplantation (HSCT). The HSCT group had a significantly higher 5-year OS rate than the non-HSCT group (46%±14% vs 29%±7%, P<0.05). There was no significant difference in the 5-year OS rate between the children without PTPN11 gene mutation and those with PTPN11 gene mutation (30%±14% vs 27%±10%, P>0.05). The Cox proportional-hazards regression model analysis showed that platelet count <40×109/L at diagnosis was an influencing factor for 5-year OS rate in children with JMML (P<0.05).@*CONCLUSIONS@#The PTPN11 gene was the most common mutant gene in JMML. Platelet count at diagnosis is associated with the prognosis in children with JMML. HSCT can improve the prognosis of children with JMML.

Two pairs of phloroglucinol enantiomers from Hypericum wightianum and their stereochemical structures / 中国中药杂志

The chemical constituents in the ethanol extract of Hypericum wightianum(Hypericaceae) were purified by column chromatography and identified via magnetic resonance imaging(NMR), high-resolution mass spectrum, and circular dichroism. A total of 22 compounds were identified, including eight polyprenylated phloroglucinols(1-8), three chromones(9-11), and three terpenoids(14-16) and so on. Among them, compounds 16 and 17 were first reported in the genus Hypericum, and compounds 1-11, 14, 15, and 19 were first isolated from H. wightianum. Compounds 1-4 were previously reported as two pairs of enantiomers. This study reported the chiral resolutions and absolute configurations of compounds 1-4 for the first time.

Genomics of next generation sequencing in pediatric B-acute lymphoblastic leukemia and its impact on minimal residual disease / 中华儿科杂志

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.

Analysis of 7 cases of pediatric acute myeloid leukemia with DEK-NUP214 fusion gene / 中华儿科杂志

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.

Clinical analysis of immunotherapy rechallenge in advanced gastric cancer / 中华肿瘤杂志

Objective: To evaluate the efficacy and influencing factors of programmed death protein 1 (PD-1) monoclonal antibody rechallenge therapy in advanced gastric cancer (GC). Methods: The clinical data of patients with advanced GC who were treated with anti-PD-1 rechallenge in Henan Cancer Hospital from January 2020 to December 2021 were collected retrospectively. The progression-free survival (PFS) was defined as the time from the first or second used of anti-PD-1 treatment to the date of disease progression or the last follow-up, named PFS(1) and PFS(2), respectively. Kaplan-Meier method and Log rank test were used for survival analysis, Cox proportional hazard model was used to analyze the influencing factors. Results: A total of 60 patients with anti-PD-1 rechallenge therapy were collected, the median follow-up time was 12.2 months. The median progression-free survival (PFS(2)) of anti-PD-1 rechallenge therapy was 2.9 months, the objective response rate (ORR) was 16.7%, and the disease control rate (DCR) was 55.0%. The median PFS(2) of the first and second anti-PD-1 identical and different rechallenge treatment was 3.5 months and 1.9 months (P=0.007) respectively. The median PFS(2) of positive PD-L1 expression in rechallenge therapy was 3.4 months, ORR was 22.7%, and DCR was 63.6%; the median PFS(2) was 4.5 months, ORR was 27.3%, and DCR was 54.5% in patients with median PFS(1)≥6 months. Multivariate analysis showed that peritoneal metastasis was independently associated with anti-PD-1 rechallenge therapy with PFS(2) (HR=2.327, 95% CI, 1.066-5.082, P=0.034). The incidence of adverse reactions in grade 1-2 and grade 3-4 of anti-PD-1 rechallenge therapy was 83.3%, and 35.0%, respectively, and the safety was controllable. Conclusion: Rechallenge therapy with anti-PD-1 is a feasible treatment in advanced GC, but the screening of suitable population for rechallenge therapy still needs prospective data analysis and verification.

Research progress in gut-skin axis and its association with traditional Chinese medicine theory / 中国中药杂志

Currently, the gut-organ axis has become a hot research topic. As increasing attention has been paid to the role of gut microbiota in the health of organs, the complex and integrated dialogue mechanism between the gastrointestinal tract and the associated microbiota has been demonstrated in more and more studies. Skin as the largest organ in the human body serves as the primary barrier protecting the human body from damage. The proposal of the gut-skin axis has established a bidirectional link between the gut and the skin. The disturbance of gut microbiota can lead to the occurrence of skin diseases, the mechanism of which is complex and may involve multiple pathways in immunity, metabolism, and internal secretion. According to the theory of traditional Chinese medicine(TCM), the connection between the intestine and the skin can be established through the lung, and the interior disorders will definitely cause symptoms on the exterior. This paper reviews the research progress in the gut-skin axis and its correlation with TCM theory and provides ideas and a basis for cli-nical treatment and drug development of skin and intestinal diseases.

Anti-aging and mechanism of 2-O-cinnamic acid magnolol / 药学学报

Magnolol, a hydroquinone containing an allyl side chain, is one of the major active components of magnolia for antioxidation and anti-aging. To enhance the anti-aging activity and improve the intramolecular hydrogen bonding of magnolol, magnolol was reacted with cinnamic acid to obtain 2-O-cinnamic acid magnolol by esterification. The anti-aging activity of magnolol 2-O-cinnamate was investigated based on Caenorhabditis elegans model. The results showed that 2-O-cinnamic acid magnolol can reduce lipofuscin accumulation in the nematode body, and the effect is better than that of magnolol. 2-O-Cinnamic acid magnolol can extend nematode lifespan, reduce ROS levels in nematodes during normal aging and oxidative stress and improve nematode stress resistance under heat stress and oxidative stress. 2-O-Cinnamic acid magnolol could induce DAF-16 translocation from the cytoplasm to the nucleus and upregulate the expression of the sod-3 gene encoding superoxide dismutase in the nematode TJ356 expressing DAF-16 fused with GFP. 2-O-Cinnamic acid magnolol did not improve the survival rate of hsp-16.2 gene deficient nematodes under oxidative stress, indicating that 2-O-cinnamic acid magnolol improves stress resistance of nematodes under oxidative stress may be associated with sod-3 and hsp-16.2. Moreover, 2-O-cinnamic acid magnolol did not extend the lifespan of daf-16 and age-1 mutants, indicating that age-1 and daf-16 are required for 2-O-cinnamic acid magnolol to delay aging. It showed that magnolol 2-O-cinnamic acid has the potential to improve antioxidant capacity and delay aging, and the mechanism may be related to the insulin/insulin-like growth factor signaling pathway.

Effect of Hippocampus kelloggi on GRP-78/PERK/ATF-4 signaling pathway of endoplasmic reticulum stress response after spinal cord injury / 国际中医中药杂志

Objective:To observe the effect of Hippocampus kelloggi on GRP-78/PERK/ATF-4 signal pathway and explore its mechanism on improving spinal cord injury. Methods:A total of 36 SD rats were randomly divided into sham operation group, model group and hippocampus group with 12 rats in each group. Only laminectomy was performed in the sham operation group. The spinal cord injury model was prepared in the model group and hippocampus group. Rats in the hippocampus group were given 10 ml/kg Hippocampus kelloggi extract by gavage for 14 days. Basso Beattie Bresnahan (BBB) score was used to evaluate the motor function of the limbs. The neuron morphology was observed by Nissl staining. The expression of GRP-78, p-PERK and ATF-4 proteins were detected by Western blot, the expression of GRP-78 and ATF-4 mRNAs was detected by qPCR, Caspase-3 and Caspase-12 were detected by ELISA, and the apoptosis was detected by TUNEL. Results:Compared with the model group, the BBB score of hippocampal group increased on the 7th, 9th, 11th and 14th day after operation ( P<0.05). For hippocampus group, the relative expression of GRP-78 (0.49 ± 0.06 vs. 0.74 ± 0.03), p-PERK (0.63 ± 0.04 vs. 0.81 ± 0.06) and ATF-4 (0.51 ± 0.06 vs. 0.69 ± 0.05) protein were significantly decreased ( P<0.05), GRP-78 mRNA (0.54 ± 0.05 vs. 0.63 ± 0.06) and ATF-4 mRNA (0.61 ± 0.06 vs. 0.78 ± 0.04) were significantly decreased ( P<0.05), the content of Caspase-3 and caspase-12 were significantly decreased ( P<0.05), and the apoptosis rate of hippocampal group was significantly decreased ( P<0.05). Conclusion:Hippocampus kelloggi can regulate the stress response of the endoplasmic reticulum after spinal cord injury by inhibiting GRP-78/PERK/ATF-4 signaling pathway to promote the repair of neurons.

Research progress on anti-tumor and tumor immunity of marine natural products / 药学学报

In recent years, the oceans have provided an important source of highly promising new anti-tumor drugs for innovation and screening, with approximately 56% of biologically active compounds being discovered to have anti-tumor effects each year. In this study, we classified and summarized the approved drugs of marine origin in terms of anti-tumor therapy, and firstly, we briefly overviewed the role of the immune system in cancer pathogenesis and discussed the current dilemma of cancer immunotherapy and highlighted the main anti-tumor targets of marine drugs. Further, with a focus on tumor immunity, we classified and outlined the history of currently approved marine original drugs by species origin, structural features, relevant pathways, and clinical application and therapy. Lastly, the limitations of current marine drug research were discussed, as well as prospects and trends in new drug development.

Comprehensive evaluation of the quality of Amomum tsao -ko based on entropy weight TOPSIS method / 中国药房

OBJECTIVE To evaluate the quality of Amomum tsao -ko from different origins and harvesting periods comprehensively. METHODS The contents of total volatile oil in A. tsao -ko were determined by volatile oil measurement method A stated in 2020 edition of Chinese Pharmacopoeia （part Ⅳ）；the contents of total flavonoids and total polyphenols in A. tsao -ko were determined by aluminum nitrate-sodium nitrite colorimetry and folin-ciocalteu method. The contents of α-pinene，β-pinene， 1，8-cineole，α-terpineol，geraniol and trans-nerolidol in the volatile oil of A. tsao -ko were determined by gas chromatography ；the contents of protocatechuate and vanillic acid in A. tsao -ko were determined by ulta high performance liquid chromatography. The above 11 indicators were selected ，and entropy weight TOPSIS method was used to comprehensively evaluate the quality of 16 batches of A. tsao -ko. RESULTS The contents of total volatile oil ，total flavonoids ，total polyphenols ，α-pinene，β-pinene， 1，8-cineole，α-terpineol，geraniol，trans-nerolidol，protocatechuate and vanillic acid in 16 batches of A. tsao -ko were 15.833 3- 28.000 0 μL/g，29.100 5-78.199 6 mg/g，6.789 8-35.797 7 mg/g，0.088 7-0.401 3 mg/g，0.106 3-0.408 0 mg/g，3.709 6-8.533 1 mg/g，0.259 8-0.599 6 mg/g，0.314 8-1.324 1 mg/g，0.272 3-0.576 4 mg/g，9.301 2-19.818 5 μg/g，8.180 9-27.666 3 μg/g， respectively. Entropy weight TOPSIS results showed that the top three of relative closeness rankings were A. tsao -ko produced by Yunnan Baoshan in July ，Yunnan Honghe in October ，Yunnan Wenshan in September ；the last three of relative closeness rankings were A. tsao -ko produced by Yunnan Dehong in September ，Yunnan Dehong in November ，Yunnan Dehong in December. CONCLUSIONS A. tsao -ko produced by Yunnan Baoshan in July ，Yunnan Honghe in October and Yunnan Wenshan in September present better quality.

Effects and molecular mechanism of exogenous L-carnitine on excessive endoplasmic reticulum stress-mediated hepatic pyroptosis in severely scald rats / 中华烧伤杂志

Objective: To investigate the effects and molecular mechanism of exogenous L-carnitine on hepatic pyroptosis mediated by excessive endoplasmic reticulum stress in severely scald rats. Methods: The experimental research method was adopted. According to the random number table (the same group method below), fifteen female Sprague Dawley rats aged 6-8 weeks were divided into sham-injury group, scald alone group, and scald+carnitine group (with 5 rats in each group), and full-thickness scald of 30% total body surface area were made on the back of rats in scald alone group and scald+carnitine group, and rats in scald+carnitine group were additionally given intraperitoneal injection of L-carnitine. At post injury hour (PIH) 72, The levels of aspartate aminotransferase (AST) and alanine dehydrogenase (ALT) of biochemical indicators of liver injury were detected by automatic biochemical analyzer with the sample number of 5. At PIH 72, liver tissue damage was detected by hematoxylin-eosin staining. At PIH 72, The mRNA levels of nucleotide-binding oligomerization domain-containing protein-like receptor family pyrin domain containing 3 (NLRP3), cysteine aspartic acid specific protease 1 (caspase-1), gasderminD (GSDMD), and interleukin 1β(IL-1β) in liver tissue as pyroptosis-related markers and glucose regulatory protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in liver tissue as endoplasmic reticulum stress-related markers were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR). Protein expression levels of GRP78, CHOP, NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue were detected by Western blotting, and the sample numbers were all 5. HepG2 cells as human liver cancer cells were divided into dimethyl sulfoxide (DMSO) group, 0.1 μmol/L tunicamycin (TM) group, 0.2 μmol/L TM group, 0.4 μmol/L TM group, and 0.8 μmol/L TM group and were treated accordingly. After 24 h of culture, cell viability was detected by cell counting kit 8, and the intervention concentration of TM was screened, and the sample number was 5. HepG2 cells were divided into DMSO group, TM alone group, and TM+carnitine group, and treated accordingly. After 24 h of culture, the protein expression levels of GRP78, CHOP, NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in cells were detected by Western blotting, and the sample numbers were all 3. Data were statistically analyzed with one-way analysis of variance and least significant difference-t test. Results: At PIH 72, the AST and ALT levels of serum in scald alone group were (640±22) and (157±8) U/L, which were significantly higher than (106±13) and (42±6) U/L in sham-injury group, respectively, with t values of -46.78 and -25.98, respectively, P<0.01. The AST and ALT levels of serum in scald+carnitine group were (519±50) and (121±10) U/L, which were significantly lower than those in scald alone group, respectively, with t values of 4.93 and 6.06, respectively, P<0.01. At PIH 72, the morphology of liver tissue of rats in sham-injury group were basically normal with no obvious inflammatory cell infiltration; compared with those in sham-injury group, the liver tissue of rats in scald alone group showed a large number of inflammatory cell infiltration and disturbed cell arrangement; compared with that in scald alone group, the liver tissue of rats in scald+carnitine group showed a small amount of inflammatory cell infiltration. At PIH 72, the mRNA expression on levels of NLRP3, caspase-1, GSDMD, and IL-1β in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 34.42, 41.93, 30.17, and 15.68, respectively, P<0.01); the mRNA levels of NLRP3, caspase-1, GSDMD, and IL-1β in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 34.40, 37.20, 19.95, and 7.88, respectively, P<0.01). At PIH 72, the protein expression levels of NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 12.28, 26.92, 5.20, 10.02, and 24.78, respectively, P<0.01); compared with those in scald alone group, the protein expression levels of NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue of rats in scald+carnitine group were significantly decreased (with t values of 10.99, 27.96, 12.69, 8.96, and 12.27, respectively, P<0.01). At PIH 72, the mRNA levels of GRP78 and CHOP in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 21.00 and 16.52, respectively, P<0.01), and the mRNA levels of GRP78 and CHOP in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 8.92 and 8.21, respectively, P<0.01); the protein expression levels of GRP78 and CHOP in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 22.50 and 14.29, respectively, P<0.01), and the protein expression levels of GRP78 and CHOP in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 14.29 and 5.33 respectively, P<0.01). After 24 h of culture, the cell survival rates of 0.1 μmol/L TM group, 0.2 μmol/L TM group, 0.4 μmol/L TM group, and 0.8 μmol/L TM group were significantly decreased than that in DMSO group (with t values of 4.90, 9.35, 18.64, and 25.09, respectively, P<0.01). Then 0.8 μmol/L was selected as the intervention concentration of TM. After 24 h of culture, compared with that in DMSO group, the protein expression levels of GRP78 and CHOP in cells in TM alone group were significantly increased (with t values of 10.48 and 17.67, respectively, P<0.01), and the protein expression levels of GRP78 and CHOP in TM+carnitine group were significantly lower than those in TM alone group (with t values of 8.08 and 13.23, respectively, P<0.05 or P<0.01). After 24 h of culture, compared with those in DMSO group, the protein expression levels of NLRP3 and GSDMD-N in cells in TM alone group were significantly increased (with t values of 13.44 and 27.51, respectively, P<0.01), but the protein expression levels of caspase-1, caspase-1/p20, and cleaved IL-1β in cells were not significantly changed (P>0.05); compared with that in TM alone group, the protein expression levels of NLRP3 and GSDMD-N in cells in TM+carnitine group were significantly decreased (with t values of 20.49 and 21.95, respectively, P<0.01), but the protein expression levels of caspase-1, caspase-1/p20, and cleaved IL-1β in cells were not significantly changed (P>0.05). Conclusions: In severely scald rats, exogenous L-carnitine may play a protective role against liver injury by inhibiting the pathways related to excessive endoplasmic reticulum stress-mediated pyroptosis.

Explore Potential Molecular Mechanism of Gegen Qinliantang in Intervention of Atherosclerosis Based on Network Pharmacology and Molecular Docking / 中国实验方剂学杂志

ObjectiveThis study aims to explore the potential molecular mechanism of Gegen Qinliantang （GQL） in the intervention of atherosclerosis （AS） based on network pharmacology and molecular docking. MethodThe active components and targets of each medicinal in GQL were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and AS-related genes from 7 databases. Thereby， the anti-AS targets of GQL were screened out. Cytoscape 3.8.0 was employed to construct the "component-target" network， and STRING the protein-protein interaction （PPI） network. Core targets were screened out with CytoNCA. R clusterProfiler was used for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of target genes， which were then visualized. Finally， molecular docking of the top ten active components with the core targets of AS was performed and the binding affinity was compared with that between atorvastatin and the core targets. ResultIn the end， 150 active components of GQL， 20 289 AS targets， and 213 common targets were retrieved， and 48 core common targets were screened out. They were mainly involved in the GO terms of nuclear receptor activity， ligand activation， and transcription factor activity and the pathways of fluid shear force and AS， advanced glycation end products-receptor for advanced glycation end products （AGE/RAGE）， interleukin-17 （IL-17）， tumor necrosis factor （TNF）， Toll-like receptor pathways and other signaling pathways closely related to AS. The molecular docking results showed that the effective components of GQL had high binding affinity to core targets of AS， and the binding affinity was even higher than that between the atorvastatin and core targets. The five groups with high binding affinity were puerarin-TNF， baicalein-inducible nitric oxide synthase 2 （NOS2）， puerarin-NOS2， and formononetin-NOS2， wogonin-NOS2. ConclusionThe above result provides new ideas for further exploration of this classical decoction.

Clinical efficacy of combined therapy in children with stage 4 neuroblastoma / 中国当代儿科杂志

OBJECTIVES@#To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma.@*METHODS@#A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021.@*RESULTS@#The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years.@*CONCLUSIONS@#Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.