Effects of Bushen formulae on bone metabolism and ENaCα,NCC and ClC-3 expression in ovariectomized rats with high salt intake / 中国病理生理杂志

AIM:To investigate the effect of Bushen formulae(BHF)on bone metabolism and its possible mechanism in ovariectomized rats with high salt intake.METHODS:According to the random number table method,80 SPF-grade Sprague-Dawley rats were divided into sham group,ovariectomy(OVX)group,medium-high-salt diet(MSD)group,high-salt diet(HSD)group,BHF group,BHF with normal saline(BHF+NS)group,BHF+MSD group,and BHF+ HSD group,with 10 rats in each group.After modeling,different diets and BHF formula interventions were administered,and the concentrations of sodium chloride added to MSD group and HSD group were 2%(w/w)and 8%(w/w),respective-ly.The dose of BHF was 7.8 g·kg-1·d-1,once a day,and the treatment lasted for 12 weeks.Bone density,bone microar-chitecture,bone parameters,bone metabolism biomarkers,bone histopathological changes,the expression of epithelial sodium channel α(ENaCα),Na-Cl cotransporter(NCC),and voltage-gated chloride channel 3(ClC-3)proteins in bone tissue were detected in each group.RESULTS:Compared with sham group,the rats in OVX group had reduced bone density and destroyed bone microstructure.Compared with OVX group,the bone microstructure in MSD and HSD groups was more significantly damaged,while the levels of bone formation markers,bone glycoprotein(BGP)and type Ⅰ procolla-gen N-terminal peptide(PINP),were significantly increased in HSD group(P<0.05).Moreover,the levels of bone re-sorption markers,such as amino-terminal cross-linked telopeptides of type Ⅰ collagen(NTX),carboxy-terminal cross-linked telopeptides of type Ⅰ collagen(CTX)and tartrate-resistant acid phosphatase(TRACP),were significantly in-creased(P<0.05),indicating that bone metabolism was in high-conversion state.High-salt diet accelerated the structural destruction of bone trabeculae,and Western blot results showed that high-salt diet caused decreases in the protein expres-sion levels of ENaCα and ClC-3 and an increase in the protein expression level of NCC in femoral tissues(P<0.05).After BHF intervention,the expression of relevant ion channels caused by high salt could be regulated to different degrees.CONCLUSION:Bushen formulae could differentially regulate the expression of relevant ion channels ENaCα,ClC-3,and NCC induced by high salt to different degrees,which has certain ameliorative and therapeutic effects on the imbalance of bone metabolism.

The Functional Role of SUMOylation in The Tumor Microenvironment / 生物化学与生物物理进展

Tumors continue to be a major challenge in human survival that we have yet to overcome. Despite the variety of treatment options available, we have not yet found an effective method. As more and more research is conducted, attention has been turned to a new field for tumor treatment—the tumor microenvironment (TME). This is a dynamic and complex environment consisting of various matrix cells surrounding cancer cells, including surrounding immune cells, blood vessels, extracellular matrix, fibroblasts, bone marrow-derived inflammatory cells, signaling molecules, and some specific cell types. Firstly, endothelial cells play a key role in tumor development and the immune system’s protection of tumor cells. Secondly, immune cells, such as macrophages, Treg cells, Th17 cells, are widely involved in various immune responses and activities in the human body, such as inflammation responses promoting survival carefully orchestrated by the tumor. Even though many studies have extensively researched the TME and found many research schemes, so far, no key effective method has been found to treat tumors by affecting the TME. The TME is a key interaction area between the host immune system and the tumor. Cells within the TME influence each other and interact with cancer cells to affect cancer cell invasion, tumor growth, and metastasis. This is a new direction for cancer treatment. In the complex environment of the TME, post-translational modifications (PTMs) of proteins have been proven to play an important role in the TME. PTMs are dynamic, strictly regulated changes to proteins that control their function by regulating their structure, spatial location, and interaction. Among PTMs, a reversible post-translational modification called SUMOylation is a common regulatory mechanism in cellular processes. It is a post-translational modification that targets lysine residues with a small ubiquitin-like modifier (SUMO) in a reversible post-translational modification manner. SUMOylation is widely involved in carcinogenesis, DNA damage response, cancer cell proliferation, metastasis, and apoptosis, playing a pivotal role in the TME, such as DNA damage repair, tumor metastasis, and also participates in immune cell differentiation, activation, and inhibition of immune cells. On the other hand, SUMO or sentrin-specific protease (SENP) inhibitors can interfere with the SUMOylation process, thereby affecting many biological processes, including immune response, carcinogenesis, cell cycle progression, and cell apoptosis, etc. In summary, this review aims to introduce the dynamic modification of protein SUMOylation on various immune cells and the application of various inhibitors, thereby exploring its role in the TME. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs. In conclusion, the TME is a complex and dynamic environment that plays a crucial role in the development and progression of tumors. Understanding the intricate interactions within the TME and the role of PTMs, particularly SUMOylation, could provide valuable insights into the mechanisms of tumor development and potentially lead to the development of novel therapeutic strategies. The study of SUMOylation and its effects on various immune cells in the TME is an exciting and promising area of research that could significantly advance our understanding of tumor biology and potentially lead to the development of more effective treatments for cancer. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs.

The effect of bivalirudin on coronary microcirculation and short-term prognosis evaluation in acute coronary syndrome patients undergoing percutaneous coronary intervention / 中国介入心脏病学杂志

Objective To compare the effects and prognosis between bivalirudin and heparin on coronary microcirculation in patients with acute coronary syndrome(ACS)during percutaneous coronary intervention(PCI).Methods A retrospective analysis was conducted on 312 ACS patients who underwent PCI treatment in the Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University from January 2020 to March 2023.General clinical data were analyzed and divided into a bivalvrudin group of 153 patients and a heparin group of 159 patients based on different anticoagulation regimens during the perioperative period.The postoperative thrombolysis in myocardial infarction(TIMI)blood flow grading,TIMI myocardial perfusion grading(TMPG),ST segment regression rate(STR)of electrocardiogram,and the number of angina pectoris episodes were observed and compared between the two groups The incidence of adverse events within 7 days after surgery,the incidence of major adverse cardiovascular events(MACE)within 3 months after surgery,and the incidence of bleeding events.Results There was no statistically significant difference in the general clinical data and intraoperative conditions between the two groups of patients(both P＞0.05).There was no statistically significant difference in TIMI blood flow grading between the two groups of patients after PCI(P=0.959).The TMPG grading of two groups of patients after PCI was statistically significant(P=0.001).The number of angina attacks and ST segment regression rate of electrocardiogram in both groups of patients after PCI were statistically significant(both P＜0.05).The incidence of adverse events within 7 days after PCI in two groups of patients was not statistically significant(P=0.285).There was no statistically significant difference in the total incidence of MACE events within 3 months after PCI between the two groups of patients(P=0.195).There was no statistically significant difference in the incidence of bleeding events within 3 months after PCI between the two groups of patients(all P＞0.05).Conclusions sivalirudin is safe and effective for PCI treatment,can improve coronary microcirculation,and does not increase the incidence of MACE events,bleeding events,and stent thrombosis events.

Application of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm / 中国当代儿科杂志

OBJECTIVES@#To investigate the role of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm (IS).@*METHODS@#A retrospective analysis was performed on 14 children with controlled IS (IS group) who were admitted to the Department of Neurology, Anhui Provincial Children's Hospital, from January 2019 to January 2023. Twelve healthy children, matched for sex and age, were enrolled as the control group. Electroencephalogram (EEG) data were analyzed for both groups to compare the features of brain network, and nonlinear dynamic indicators were calculated, including approximate entropy, sample entropy, permutation entropy, and permutation Lempel-Ziv complexity.@*RESULTS@#Brain functional connectivity showed that compared with the control group, the IS group had an increase in the strength of functional connectivity, and there was a significant difference between the two groups in the connection strength between the Fp2 and F8 channels (P<0.05). The network stability analysis showed that the IS group had a significantly higher network stability than the control group at different time windows (P<0.05). The nonlinear dynamic analysis showed that compared with the control group, the IS group had a significantly lower sample entropy of Fz electrode (P<0.05).@*CONCLUSIONS@#Abnormalities in brain network and sample entropy may be observed in some children with controlled IS, and it is suggested that quantitative EEG analysis parameters can serve as neurological biomarkers for evaluating brain function in children with IS.

Biometric investigation of ocular components in various types of anisometropia in school-age children / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the differences and correlations between different types of anisometropia, binocular visual acuity and biological parameters in school-age children.METHODS: A total of 128 school-age children(6-12 years)with mild-to-moderate anisometropia were retrospectively analyzed. Subjects were divided into five groups according to anisometropia type. All participants underwent cycloplegic refraction, A-scan ultrasound biometry, and corneal topography. Refractive status, best-corrected visual acuity(BCVA), anterior chamber depth(ACD), lens thickness(LT), vitreous chamber depth(VCD), axial length(AL), corneal radius(CR), and ratio of AL and CR(AL/CR)were recorded. Kruskal-Wallis and Spearman rank correlation tests were then used for statistical analysis.RESULTS: Hyperopic anisometropia had the greatest binocular vision difference(0.14±0.20). Myopic anisometropia had the greatest asymmetry in AL and VCD(0.56±0.41 and 0.56±0.39 mm, respectively). Anisometropia was positively correlated with BCVA, VCD, AL, and AL/CR(r=0.266, 0.379, 0.350, 0.263, respectively; P&#x0026;#x003C;0.05), and it was not significantly correlated with LT and CR(r=-0.019,-0.069, respectively; P&#x0026;#x003E;0.05), while no parameters had a statistically significant correlation with anisometropia in each group.CONCLUSION: School-age children with hyperopic anisometropia showed the greatest difference of binocular acuity in the four types of anisometropia. The inter-ocular differences of biometric parameters in simple hyperopic or myopic anisometropia were mainly attributed to the asymmetry of VCD and AL, while the differences in ocular parameters were not statistically significant in school-age children with astigmatic anisometropia.

Inhibitory effect of sodium ferulate on inflammatory response in migraine rats based on c-Jun N-terminal kinase / p38 mitogen-activated protein kinase signaling pathway / 解剖学报

[Abstract] Objective To explore the inhibitory effect of sodium ferulate (SF) on the inflammatory response in migraine rats by regulating the c-Jun N-terminal kinase (JNK) / p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Methods The migraine rat model was prepared by intraperitoneal injection of nitroglycerin. After successful modeling, the rats were randomly grouped into model group, SF low dose (SF-L) group (50 mg/ kg), SF high dose (SF-H) group (100 mg/ kg), SF+JNK inhibitor (SF + SP600125) group (SF 100 mg/ kg +SP600125 10 mg/ kg), and SF+JNK activator [SF + anisomycin(AN)] group (SF 100 mg/ kg +AN 5 mg/ kg), 12 in each group, another 12 SD rats without treatment were taken as blank group. The behavioral changes of the rats in each group were observed 24 hours after the administration, the levels of 5-hydroxytryptamine (5-HT), nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum were detected by ELISA, the neuronal apoptosis in brain tissue was observed by TUNEL staining, immunohistochemistry was used to evaluate the expressions of TNF-α, IL-6 and calcitonin gene-related peptide (CGRP) in brain tissue, Western blotting was used to detect the expressions of JNK/ p38 MAPK pathway-related proteins in brain tissue. Results Compared with the blank group, the number of times of scratching the head and climbing the cage of the rats in the model group increased significantly, and the apoptosis rate of neurons increased significantly; the content of 5-HT in serum decreased significantly, and the levels of NO, TNF-α and IL-6 increased significantly; the expressions of TNF-α, IL-6 and CGRP, and the ratios of phosphorylated JNK (p-JNK) / JNK and phosphorylated p38 MAPK(p-p38 MAPK) / p38 MAPK in brain tissue obviously increased (all P<0. 05). Compared with the model group, the number of times of scratching the head and the times of climbing the cage of the rats in the SF-L group and the SF-H group reduced significantly, and the neuron apoptosis rate reduced significantly; the content of 5-HT in serum increased significantly, and the levels of NO, TNF-α and IL-6 decreased significantly; the expressions of TNF-α, IL-6 and CGRP, and the ratios of p-JNK/ JNK and p-p38 MAPK/ p38 MAPK in brain tissue obviously decreased (all P<0. 05). Compared with SF-H group, the protective effect of SF on migraine rats in SF+SP600125 group enhanced significantly; the protective effect of SF on migraine rats in the SF+AN group reversed significantly. Conclusion SF may inhibit the expression of JNK/ p38 MAPK signaling pathway, effectively inhibit neurogenic inflammatory response in migraine rats, reduce neuronal apoptosis, and achieve a protective effect on migraine rats.

Influencing factors of negative conversion time of nucleic acid detection in 228 patients infected with Omicron variant of SARS-CoV-2 in Shanghai / 中国热带医学

@#Abstract: Objective To analyze and compare the effects of different clinical characteristics on the negative conversion time of nucleic acid detection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection, and to provide a scientific basis for the isolation and treatment of coronavirus disease 2019 (COVID-19). Methods　The epidemiological and clinical data of 228 mild SARS-CoV-2 Omicron variant infected patients diagnosed in Shanghai were retrospectively collected from April 27, 2022 to June 8, 2022 in Wujiaochang designated Hospital, Yangpu District, Shanghai. The negative conversion time of nucleic acid detection was used as the outcome variable, and the patients were divided into A (≤18 days) and B (>18 days). Univariate and multivariate logistic regression analysis were used to analyze the influencing factors of the negative conversion time of nucleic acid detection. Results　The mean nucleic acid conversion time of 228 patients was (18.7±12.1) d, with the median time of 18 (2-46) d. Among them, 120 patients in group A had an average nucleic acid conversion time of (13.2±2.0) d, and 108 cases in group B had an average nucleic acid conversion time of (20.8±1.3) d. Univariate analysis showed that there were no statistically significant differences in the effects of hypertension, coronary heart disease, diabetes, hypokalemia, malignant tumors, neuropsychiatric diseases, chronic digestive diseases on the negative nucleic acid conversion time (P>0.05); however, there were significant differences in the effects of combined cerebrovascular disease, leukopenia, chronic respiratory system diseases and vaccination on the negative nucleic acid conversion time (P<0.05). Further multivariate logistic regression analysis revealed that the combination of chronic respiratory diseases and non-vaccination were significant risk factors for prolongation of negative nucleic acid conversion time (P<0.05). Conclusions The results of this study show that gender, age and whether hypertension, coronary heart disease, diabetes mellitus, hypokalemia, malignant tumor, neuropsychiatric disease and chronic digestive disease have no significant effect on the nucleic acid conversion time, whereas chronic respiratory disease and no vaccination are significantly correlated with the prolongation of nucleic acid conversion time in SARS-CoV-2 Omicron-infected patients.

Ketogenic diet improves low temperature tolerance in mice by up-regulating PPARα in the liver and brown adipose tissue / 生理学报

The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα-/-+ND) group and ketogenic diet (PPARα-/-+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα-/-+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα-/-+ND group, the PPARα-/-+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.

Inhibition of glutaminolysis alleviates myocardial fibrosis induced by angiotensin II / 生理学报

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.

Mechanism of artesunate on bone destruction in experimental rheumatoid arthritis based on transcriptomics and network pharmacology / 中国中药杂志

The present study investigated the mechanism of artesunate in the treatment of bone destruction in experimental rheumatoid arthritis(RA) based on transcriptomics and network pharmacology. The transcriptome sequencing data of artesunate in the inhibition of osteoclast differentiation were analyzed to obtain differentially expressed genes(DEGs). GraphPad Prism 8 software was used to plot volcano maps and heat maps were plotted through the website of bioinformatics. GeneCards and OMIM were used to collect information on key targets of bone destruction in RA. The DEGs of artesunate in inhibiting osteoclast differentiation and key target genes of bone destruction in RA were intersected by the Venny 2.1.0 platform, and the intersection target genes were analyzed by Gene Ontology(GO)/Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment. Finally, the receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model and collagen-induced arthritis(CIA) model were established. Quantitative real time polymerase chain reaction(q-PCR), immunofluorescence, and immunohistochemistry were used to verify the pharmacological effect and molecular mechanism of artesunate in the treatment of bone destruction in RA. In this study, the RANKL-induced osteoclast differentiation model in vitro was established and intervened with artesunate, and transcriptome sequencing data were analyzed to obtain 744 DEGs of artesunate in inhibiting osteoclast differentiation. A total of 1 291 major target genes of bone destruction in RA were obtained from GeneCards and OMIM. The target genes of artesunate in inhibiting osteoclast differentiation and the target genes of bone destruction in RA were intersected to obtain 61 target genes of artesunate against bone destruction in RA. The intersected target genes were analyzed by GO/KEGG enrichment. According to the results previously reported, the cytokine-cytokine receptor interaction signaling pathway was selected for experimental verification. Artesunate intervention in the RANKL-induced osteoclast differentiation model showed that artesunate inhibited CC chemokine receptor 3(CCR3), CC chemokine receptor 1(CCR1) and leukemia inhibitory factor(LIF) mRNA expression in osteoclasts in a dose-dependent manner compared with the RANKL-induced group. Meanwhile, the results of immunofluorescence and immunohistochemistry showed that artesunate could dose-dependently reduce the expression of CCR3 in osteoclasts and joint tissues of the CIA rat model in vitro. This study indicated that artesunate regulated the CCR3 in the cytokine-cytokine receptor interaction signaling pathway in the treatment of bone destruction in RA and provided a new target gene for the treatment of bone destruction in RA.

MiR-340 mediates the involvement of high mobility group box 1 in the pathogenesis of liver fibrosis / 中华肝脏病杂志

Objective: To explore the pathogenic mechanism of the miR-340/high mobility group box 1 (HMGB1) axis in the formation of liver fibrosis. Methods: A rat liver fibrosis model was established by injecting CCl(4) intraperitoneally. miRNAs targeting and validating HMGB1 were selected with gene microarrays after screening the differentially expressed miRNAs in rats with normal and hepatic fibrosis. The effect of miRNA expressional changes on HMGB1 levels was detected by qPCR. Dual luciferase gene reporter assays (LUC) was used to verify the targeting relationship between miR-340 and HMGB1. The proliferative activity of the hepatic stellate cell line HSC-T6 was detected by thiazolyl blue tetrazolium bromide (MTT) assay after co-transfection of miRNA mimics and HMGB1 overexpression vector, and the expression of extracellular matrix (ECM) proteins type I collagen and α-smooth muscle actin (SMA) was detected by western blot. Statistical analysis was performed by analysis of variance and the LSD-t test. Results: Hematoxylin-eosin and Masson staining results showed that the rat model of liver fibrosis was successfully established. Gene microarray analysis and bioinformatics prediction had detected eight miRNAs possibly targeting HMGB1, and animal model validation had detected miR-340. qPCR detection results showed that miR-340 had inhibited the expression of HMGB1, and a luciferase complementation assay suggested that miR-340 had targeted HMGB1. Functional experiments results showed that HMGB1 overexpression had enhanced cell proliferation activity and the expression of type I collagen and α-SMA, while miR-340 mimics had not only inhibited cell proliferation activity and the expression of HMGB1, type I collagen, and α-SMA, but also partially reversed the promoting effect of HMGB1 on cell proliferation and ECM synthesis. Conclusion: miR-340 targets HMGB1 to inhibit the proliferation and ECM deposition in hepatic stellate cells and plays a protective role during the process of liver fibrosis.

Research advances on the role and mechanism of microRNA in hypertrophic scar / 中华烧伤杂志

Hypertrophic scar (HS) affects the function and beauty of patients, and brings a heavy psychological burden to patients. However, the specific pathogenesis mechanism of HS in molecular biology level is not yet clear, and this disease is still one of the clinical diseases difficult to prevent and cure. MicroRNA (miR) is a family of single-stranded endogenous noncoding RNAs that can regulate gene expression. The abnormal transcription of miR in hypertrophic scar fibroblasts can affect the transduction and expression of downstream signal pathway or protein, and the exploration of miR and its downstream signal pathway and protein helps deeply understand the occurrence and development mechanism of scar hyperplasia. This article summarized and analyzed how miR and multiple signal pathways involve in the formation and development of HS in recent years, and further outlined the interaction between miR and target genes in HS.

Effects of Ranibizumab on ocular biological parameters in the treatment of retinopathy of prematurity / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of intravitreal ranibizumab injection on ocular parameters in the treatment of retinopathy of prematurity(ROP), and analyze its relationship with birth weight(BW)and postmenstrual age(PMA).METHODS: A total of 98 premature infants who received routine ROP screening at Northwest Women's and Children's Hospital from January 1, 2016 to January 31, 2022 were selected, and they were divided into ROP group(49 cases)and non-ROP group(49 cases)according to the results of Retcam3 fundus screening. All children in ROP group were treated with intravitreal ranibizumab injection, with an average PMA of 38.02±3.03 weeks. The ocular parameters were measured at the PMA of 0 month(40 weeks±14d), 3 months(52 weeks±28d)and 6 months(64 weeks±28d), respectively.RESULTS: There was no difference in axial length(AL), anterior chamber depth(ACD), lens thickness(LT), vitreous length(VL)and central corneal thickness(CCT)between ROP group and non-ROP group at the PMA of 0 month(P&#x003E;0.05); At the PMA of 3 and 6 months, ACD in ROP group was higher than that in non-ROP group, and LT was lower than that in non-ROP group(P&#x003C;0.05); at the PMA of 6 months, AL and VL in ROP group were lower than those in non-ROP group(P&#x003C;0.05). AL, ACD and VL were positively correlated with PMA in ROP group and non-ROP group, while CCT was negatively correlated with PMA; there was a positive correlation between LT and PMA in children without ROP. There was no correlation among LT, BW and PMA in ROP group.CONCLUSION: The ocular development of children with early ROP(PMA 0～6 months)treated by intravitreal ranibizumab injection is slower than that of premature infants without ROP, and BW and PMA are the main influencing factors of ocular parameters of premature infants.

Spinal metastases combined with leptomeningeal metastasis: A case report / 北京大学学报(医学版)

Spinal metastases (SM) is the commonest form of solid tumors osseous metastasis, for which surgical dissection is often performed when combined with spinal cord compression. Leptomeningeal metastasis (LM) results from dissemination of cancer cells to both the leptomeninges (pia and arachnoid) and cerebrospinal fluid (CSF) compartment. The spread of LM may occur via multiple routes, such as hematogenous, direct infiltration from metastatic brain lesions, or via iatrogenic seeding of CSF. Signs and symptoms associated with LM are generalized and various while early diagnosis of LM is challenging. Cytological evaluation of the CSF and gadolinium enhanced MRI brain and spine is the gold standard for diagnosing LM and CSF can help assess treatment response. While a number of other potential CSF biomarkers have been investigated both for the diagnosis as well as monitoring of LM, none have been established as a component of the standard evaluation of all LM or suspected LM patients. Management goals of LM include improving patient's neurologic function, quality of life, preventing further neurologic deterioration and prolonging survival. In many cases, it may be reasonable to pursue a palliative and comfort focused course, even from the initial LM diagnosis. Surgery is not recommended considering the risk of seeding with cerebrospinal fluid. A diagnosis of LM carries a poor prognosis with an estimated median survival of only 2-4 months despite therapy. Spinal metastases combined with leptomeningeal metastasis (SM+LM) is not uncommon and its treatment is similar to LM. LM can appear at the same time as SM or directly invaded by SM, which is thought regarding the pathophysiology of LM remains speculative and not systematically studied. The present article reports a 58-year-old woman who was first diagnosed with SM, but worsened after surgery repeated MRI examinations confirmed coexisting LM. Relevant literature was reviewed to summarize the epidemiology, clinical manifestations, imaging characteristics, diagnosis and treatment of SM+LM, so as to improve the understanding of the disease and promote early diagnosis. It should be vigilant to merge LM for the patient with SM when atypical clinical manifestations, rapid disease progression or inconsistent with imaging occurred. Repeated examinations of cerebrospinal fluid cytology and enhanced MRI should be considered when SM+LM is suspected to achieve timely adjustment of diagnosis and treatment strategy for better prognosis.

Efficacy and safety of fourth-generation CD19 CAR-T expressing IL7 and CCL19 along with PD-1 monoclonal antibody for relapsed or refractory large B-cell lymphoma / 中华血液学杂志

Objective: This study systematically explore the efficacy and safety of fourth-generation chimeric antigen receptor T-cells (CAR-T), which express interleukin 7 (IL7) and chemokine C-C motif ligand 19 (CCL19) and target CD19, in relapsed or refractory large B-cell lymphoma. Methods: Our center applied autologous 7×19 CAR-T combined with tirelizumab to treat 11 patients with relapsed or refractory large B-cell lymphoma. The efficacy and adverse effects were explored. Results: All 11 enrolled patients completed autologous 7×19 CAR-T preparation and infusion. Nine patients completed the scheduled six sessions of tirolizumab treatment, one completed four sessions, and one completed one session. Furthermore, five cases (45.5%) achieved complete remission, and three cases (27.3%) achieved partial remission with an objective remission rate of 72.7%. Two cases were evaluated for disease progression, and one died two months after reinfusion because of uncontrollable disease. The median follow-up time was 31 (2-34) months, with a median overall survival not achieved and a median progression-free survival of 28 (1-34) months. Two patients with partial remission achieved complete remission at the 9th and 12th months of follow-up. Therefore, the best complete remission rate was 63.6%. Cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome were controllable, and no immune-related adverse reactions occurred. Conclusion: Autologous 7×19 CAR-T combined with tirelizumab for treating relapsed or refractory large B-cell lymphoma achieved good efficacy with controllable adverse reactions.

Cloning and expression analysis of wpHSP90 gene from Whitmania pigra at different temperatures / 中国中药杂志

HSP90 is a widely distributed molecular chaperone that participates in a variety of cellular processes and plays an important role in the meiosis of germ cells. However, its role in the gonadal development of hermaphroditic Whitmania pigra is not yet clear. To explore the effect of HSP90 on the germ cell development of Wh. Pigra, this study cloned the wpHSP90 gene, performed bioinformatics analysis, and measured its expression levels. The results showed that the cloned wpHSP90 was 2 592 bp in length, with an open reading frame(ORF) of 2 373 bp, encoding 790 amino acids. Prediction analysis revealed 85 phosphorylation modification sites on serine, threonine, and tyrosine residues of the wpHSP90 protein. Structural domain prediction and multiple sequence alignment results showed that wpHSP90 contained two conserved domains of HSP90 and exhibited the highest homology with Helobdella robusta, with a sequence similarity of 80.72%. RT-qPCR results showed that the relative expression level of wpHSP90 in the gonads of 5-month-old Wh. pigra was positively correlated with temperature within the range of 12 ℃ to 28 ℃. The expression level in the female gonads was significantly higher than in the male gonads and correlated with the trend of germ cell development in the ovaries and testes. In conclusion, wpHSP90 may be involved in regulating the development of germ cells, particularly oocytes, in Wh. pigra. This study provides a reference for further research on the gonadal development mechanism in Wh. pigra.

Research progress on electrical impedance tomography in pulmonary perfusion / 生物医学工程学杂志

Electrical impedance tomography (EIT) is an emerging technology for real-time monitoring based on the impedance differences of different tissues and organs in the human body. It has been initially applied in clinical research as well as disease diagnosis and treatment. Lung perfusion refers to the blood flow perfusion function of lung tissue, and the occurrence and development of many diseases are closely related to lung perfusion. Therefore, real-time monitoring of lung perfusion is particularly important. The application and development of EIT further promote the monitoring of lung perfusion, and related research has made great progress. This article reviews the principles of EIT imaging, lung perfusion imaging methods, and their clinical applications in recent years, with the aim of providing assistance to clinical and scientific researchers.

Recombinant Schistosoma japonicum egg ribonuclease SjCP1412 inhibits the activation of LX-2 hepatic stellate cells in vitro / 中国血吸虫病防治杂志

Objective To investigate the effect of recombinant Schistosoma japonicum egg ribonuclease SjCP1412 (rSjCP1412) on proliferation, cell cycle, apoptosis and activation of human hepatic stellate cells LX-2 in vitro, and explore the underlying mechanisms. Methods The rSjCP1412 protein was expressed in Escherichia coli BL21 by prokaryotic expression, and the highly purified soluble rSjCP1412 protein was prepared by Ni NTA affinity chromatography and urea gradient refolding dialysis. Yeast RNA was digested using 12.5, 25.0, 50.0 µg rSjCP1412 proteins at 37 °C for 2, 3, 4 h, and the enzymatic products were electrophoresed on 1.5% agarose gel to observe the RNAase activity of rSjCP1412 protein. The proliferation of LX-2 cells stimulated by different doses of rSjCP1412 protein for 48 hours was measured using CCK-8 assay, and the apoptosis of LX-2 cells stimulated by different doses of rSjCP1412 protein for 48 hours was detected using the Annexin V-FITC/PI double staining, while the percentage of LX-2 cells at G0/G1, S and G2/M phases of cell cycle following stimulation with different doses of rSjCP1412 protein for 48 h was detected by DAPI staining. The type I collagen, type III collagen and α-smooth muscle actin (α-SMA) mRNA expression was quantified using quantitative florescent real-time PCR (qPCR) assay and Western blotting at transcriptional and translational levels in LX-2 cells following stimulation with different doses of rSjCP1412 protein for 48 h, while soluble egg antigen (SEA) served a positive control and PBS without rSjCP1412 protein as a normal control in the above experiments. The expression of collagen I, α-SMA and Smad4 protein was determined using Western blotting in LX-2 cells following stimulation with rSjCP1412 protein, transforming growth factor-β1 (TGF-β1) alone or in combination, to examine the signaling for the effect of rSjCP1412 protein on LX-2 cells. Results The rSjCP1412 protein was successfully expressed and the highly purified soluble rSjCP1412 protein was prepared, which had a RNase activity. Compared with the normal group, the survival rates of LX-2 cells significantly decreased post-treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein and SEA for 48 h (F = 22.417 and 20.448, both P values < 0.05). The apoptotic rates of LX-2 cells significantly increased post-treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h (F = 11.350, P < 0.05), and treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h resulted in arrest of LX-2 cells in G0/G1 phase (F = 20.710, P < 0.05). Treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h caused a significant reduction in relative expression levels of collagen I (F = 11.340, P < 0.05), collagen III (F = 456.600, P < 0.05) and α-SMA mRNA (F = 23.100, P < 0.05) in LX-2 cells, and both rSjCP1412 protein and SEA treatment caused a significant reduction in collagen I (F = 1 302.000, P < 0.05), α-SMA (F = 49.750, P < 0.05) and Smad4 protein expression (F = 52.420, P < 0.05) in LX-2 cells. In addition, rSjCP1412 protein treatment inhibited collagen I (F = 66.290, P < 0.05), α-SMA (F = 31.300, P < 0.05) and Smad4 protein expression (F = 27.010, P < 0.05) in LX-2 cells activated by TGF-β1. Conclusion rSjCP1412 protein may induce apoptosis of LX-2 cells and inhibit proliferation, cell cycle and activation of LX-2 cells through down-regulating Smad4 signaling molecules.

Physiologically based pharmacokinetic modeling of the inhibitory effect of dapagliflozin on intestinal and renal SGLT / 药学学报

This study establishes and optimizes the physiologically based pharmacokinetics (PBPK) model for dapagliflozin, predicts the drug distribution into relevant tissues, and calculates the inhibitory effect on the sodium-glucose cotransporters (SGLTs) in the intestine and renal proximal tubule. Based on literature data, a PBPK model for oral administration in healthy adults was established and the predicted blood concentration-time curve characteristics, the main pharmacokinetic parameters (PK), and drug excretion in urine were compared with the published data. To verify and optimize the model and verify the accuracy of the tissue distribution and concentration predictions, a pharmacodynamics model (PD) was established. Urine glucose excretion (UGE) was simulated at the corresponding times. The characteristics of the drug-time curve predicted by the model are similar to those of the measured curve, and the ratio of the main PK parameters to the measured values is within a two-fold range; the accuracy of the established PBPK model is good. The maximal inhibition obtained with 10 mg of dapagliflozin on the duodenum and jejunum segment sodium-glucose co-transporter 1 (SGLT1s) was 1.6%-4.7%, and the inhibition rate of the sodium-glucose co-transporter 2 (SGLT2s) in the proximal tubule of the kidney was as high as 99.9%. At a dose of 10 mg, dapagliflozin delayed intestinal glucose absorption while occupying most of the sites (99.9%) of the renal sodium-glucose cotransporter 2 and inhibiting its glucose reabsorption. This physiological-pharmacokinetic model for dapagliflozin in healthy adults can provide meaningful guidance for exploring pharmacological mechanisms and potential toxicity of gliflozin by simulating drug distribution in different tissues.

Determination of acetone and butanone in urine of occupational populations by headspace-gas chromatography / 预防医学

Objective @#To establish a headspace-gas chromatography ( HS-GC ) method for the determination of acetone and butanone, the biomarkers of occupational exposure to isopropanol and butanone, in urine of occupational populations. @*Methods @#Urine samples at 5.0 mL were transferred to a headspace bottle, added with 2.0 g anhydrous sodium sulfate, sealed immediately, and placed in a headspace sampler-gas chromatograph-mass spectrometer. Following heating at 60 ℃ for 30 min, 0.5 mL urine samples were injected and separated with the DB-FFAP capillary chromatographic column, and determined with the flame ionization detector. In addition, the retention time and peak area were determined. @*Results @#The peak area appeared a linear relationship with mass concentrations of acetone at 0.16-80 mg/L and butanone at 0.03-16 mg/L (correlation coefficient, 0.999 9), with detection limits of 0.009 and 0.004 mg/L, quantitation limits of 0.03 and 0.02 mg/L, respectively. The mean recovery rates of spiked samples were 93.67%-99.37% and 91.18%-94.41% for low, medium and high concentrations of acetone and butanone, and the relative standard deviations of 1.53%-3.69% and 2.54%-6.58%, respectively. @*Conclusion @#A highly sensitive and repeatable HS-GC method is successfully established for simultaneous determination of acetone and butanone in urine samples by optimizing sample pretreatment and separation, which is feasible for qualitative and quantitative analyses of acetone and butanone in urine.