Historical Evolution and Key Information Research on Pediatric Famous Classical Formula Yigongsan / 中国实验方剂学杂志

Yigongsan is derived from Xiaoer Yaozheng Zhijue written by QIAN Yi in the Northern Song dynasty， which is the No. 3 formula in the Catalogue of Ancient Famous Classical Formulas（The Second Batch of Pediatrics） released by the National Administration of Traditional Chinese Medicine（TCM） in September 2022， and it can be developed as a class 3.1 new TCM drug. By referring to ancient medical books and modern literature， this study conducted herbal textual research on Yigongsan from five aspects， including historical evolution， origin and processing， dosage conversion， usage and preparation methods， and functional application， then formed the key information table of this formula， in order to provide reference for the development of reference samples and preparations of Yigongsan. Based on the results of the study， it is recommended that Panax ginseng should be removed the basal part of stem（rhizoma）， Poria cocos should be removed the peel， Citrus reticulata should be cut into shreds and Glycyrrhiza uralensis should be used. According to 4.13 g/Qian（钱）， 1 g/slice for ginger， 3 g for each jujube and 300 mL/Zhan（盏）， the doses of Ginseng Radix， Poria， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma， Citri Reticulatae Pericarpium， Zingiberis Rhizoma Recens， Jujubae Fructus were 1.652， 1.652， 1.652， 1.652， 1.652， 5， 6 g， and the total amount was 19.26 g. The decocting method was to crush the medicinal materials into fine powder with 50-80 mesh， add 300 mL of water and decoct to 210 mL for each dose， then remove the dregs and take it warmly. This formula was recorded in ancient books as the main treatment for the cold-deficiency of spleen and stomach， and Qi stagnation in children with vomiting and diarrhea and lack of appetite. It has been flexibly applied by later generations of physicians， and is often used to treat anorexia， inflammation of the digestive tract， diarrhea and other diseases in children.

Efficacy and safety of sofosbuvir/velpatasvir alone or in combination with ribavirin in treatment of patients with genotype 3B HCV/HIV infection / 临床肝胆病杂志

ObjectiveTo investigate the efficacy and safety of sofosbuvir/velpatasvir alone or in combination with ribavirin in Chinese patients with genotype 3B HCV/HIV infection. MethodsA total of 299 patients with genotype 3B HCV/HIV infection who attended The Third People’s Hospital of Kunming from January 2017 to December 2020 were enrolled and treated with sofosbuvir/velpatasvir alone or in combination with ribavirin for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The patients were evaluated in terms of sustained virologic response at 12 weeks after treatment （SVR12） and adverse reactions. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups； the Agresti-Coull method was used to evaluate the 95% confidence interval （CI） of SVR12； univariate and multivariate non-conditional logistic regression analyses were used to investigate the influencing factors for SVR. ResultsThe 299 patients with genotype 3B HCV/HIV infection had a mean age of 43.92±6.84 years， among whom the male patients accounted for 77.3% （231/299）， the patients with liver cirrhosis accounted for 36.5% （109/299）， the patients with a history of antiviral therapy accounted for 13.4% （40/299）， and the patients receiving sofosbuvir/velpatasvir combined with ribavirin accounted for 27.8% （83/299）. The overall SVR was 87.0% （260/299） for all patients， and there was no significant difference in SVR12 between the patients receiving sofosbuvir/velpatasvir alone and those receiving sofosbuvir/velpatasvir combined with ribavirin （87.5% vs 85.5%， χ2=0.203， P=0.653）. There was a significant difference in SVR12 between the patients without liver cirrhosis and those with liver cirrhosis （90.0% vs 81.7%， χ2=4.256， P=0.039）， and the patients receiving antiviral therapy for the first time had a significantly higher SVR12 than the treatment-experienced patients （93.4% vs 45.0%， χ2=71.670， P<0.001）. The univariate and multivariate logistic regression analyses showed that platelet count （odds ratio ［OR］=0.957， 95%CI： 0.931 — 0.984， P=0.002）， liver stiffness measurement （OR=1.446， 95%CI： 1.147 — 1.822， P=0.002）， and experience in treatment （OR=13.807， 95%CI： 2.970 — 64.174， P=0.001） were independent influencing factors for SVR in patients with genotype 3B HCV/HIV infection. There were 41 cases of serious adverse events， all of which occurred within 2 weeks after antiviral therapy， and 28 cases were resolved without drug withdrawal or active treatment， while 13 cases were not resolved after active treatment and were resolved after the antiviral drugs were stopped for 2‍ ‍—‍ ‍5 days， with no similar reactions observed when the drugs were used again after remission. ConclusionSofosbuvir/velpatasvir alone or in combination with ribavirin has relatively good efficacy and safety in patients with genotype 3B HCV/HIV infection.

Quantitative analysis of macular capillaries in diabetic patients using optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To quantify early changes of macular capillary parameters in type 2 diabetic patients using optical coherence tomography angiography(OCTA).METHODS: Retrospective case study. A total of 49 healthy subjects, 52 diabetic patients without retinopathy(noDR)patients, and 43 mild nonproliferative diabetic retinopathy(mNPDR)patients were recruited. Capillary perfusion density, vessel length density(VLD), and average vessel diameter(AVD)were calculated from macular OCTA images(3 mm×3 mm)of the superficial capillary plexus after segmenting large vessels and the deep capillary plexus. Parameters were compared among control subjects, noDR, and mNPDR patients. The area under the receiver operating characteristic curve estimated the abilities of these parameters to detect early changes of retinal microvascular networks.RESULTS: Significant differences were found in the VLD and AVD among the three groups(P&#x0026;#x003C;0.001). Compared with the control group, the noDR group had significantly higher AVD(P&#x0026;#x003C;0.05). VLD of both layers in patients of mNPDR group was significant decreased compared with that of noDR group(all P&#x0026;#x003C;0.01). Deep AVD had a higher area under the curve(AUC)of 0.796 than other parameters to discriminate the noDR group from the healthy group. Deep AVD had the highest AUC of 0.920, followed by that of the deep VLD(AUC=0.899)to discriminate the mNPDR group from the healthy group.CONCLUSIONS: NoDR patients had wider AVD than healthy individuals and longer VLD than mNPDR patients in both layers. When compared with healthy individuals, deep AVD had a stronger ability than other parameters to detect early retinal capillary impairments in noDR patients.

Analysis of cerebral gray matter structure in multiple sclerosis and neuromyelitis optica / 解剖学报

Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.

Impact of autonomic nerve function on motor function in patients with post-stroke depression / 中国康复理论与实践

ObjectiveTo explore the impact of autonomic nerve function on motor function in patients with post-stroke depression (PSD) from the perspective of regional homogeneity (ReHo). MethodsFrom January to December, 2020, a total of 60 inpatients and outpatients with cerebral infarction in the Affiliated Brain Hospital of Nanjing Medical University were divided into control group (n = 30) and PSD group (n = 30). Two groups were assessed using Fugl-Meyer Assessment (FMA), modified Barthel Index (MBI) and Hamilton Depression Scale (HAMD). Heart rate variability (HRV) was measured. Ten patients in each group were selected randomly to undergo resting state functional magnetic resonance imaging (rs-fMRI) to calculate ReHo. ResultsAll HRV indices were lower in PSD group than in the control group (|t| > 2.092, P < 0.05). In PSD group, FMA and MBI scores showed positive correlations with 24-hour standard deviation of normal-to-normal R-R intervals (SDNN), the root mean square of successive differences between normal heartbeats over 24 hours (RMSSD), the percentage of differences between adjacent normal R-R intervals over 24 hours that were greater than 50 ms (PNN50), total power (TP), very low frequency power (VLF) and low frequency power (LF) (r > 0.394, P < 0.05), and showed negative correlations with HAMD scores (|r| > 0.919, P < 0.001). HAMD scores in PSD group were negatively correlated with SDNN, RMSSD, PNN50, TP and VLF (|r| > 0.769, P < 0.001). Compared with the control group, the ReHo increased in PSD group in the right rectus gyrus (142 voxels, t = 6.575), the left medial and paracingulate gyri (204 voxels, t = 4.925) (GRF correction, P-Voxel < 0.005，P-Cluster < 0.05); and reduced in the right cerebellum (191 voxels, t = -6.487), the left middle temporal gyrus (140 voxels, t = -5.516), and the left precentral gyrus (119 voxels, t = -4.764) (GRF correction, P-Voxel < 0.005，P-Cluster < 0.05) in PSD group. ConclusionAutonomic nerve function is related to motor dysfunction in patients with PSD. The modulation of emotional, cognitive and motor brain regions by the autonomic nervous system may play a role in influencing the motor function in patients with PSD.

Analysis of Chemical Components and Tissue Distribution of Lujiao Formula Based on UPLC-Q-Orbitrap-MS / 中国实验方剂学杂志

ObjectiveTo qualitatively analyze the chemical constituents and their tissue distribution in Lujiao formula based on ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）. MethodThe separation was performed on an ACQUITY UPLC® BEH C18 column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-methanol（B） in a gradient elution（0-2 min， 4%B； 2-6 min 4%-12%B； 6-38 min， 12%-70%B； 38-38.5 min， 70%B； 38.5-39 min， 70%-95%B； 39-43 min， 95%B； 43-43.1 min， 95%-4%B； 43.1-45 min， 4%B）， the flow rate was 0.3 mL·min-1 with the column temperature of 40 ℃ and the injection volume of 5 µL. The data were acquired by an electrospray ionization（ESI） in the full scanning mode of positive and negative ions， the scanning rang was set at m/z 100-1 500， the collision energies were 10， 20， 40 eV. Retention time， precise relative molecular mass and secondary mass spectrometry fragment ions were used to identify the compounds in Lujiao formula and analyze their tissue distribution， combing with self-established database and comparing with standard substances and published literature data. ResultA total of 260 compounds， including 156 flavonoids， 43 terpenoids， 18 coumarins， 13 organic acids， 7 phenylethanoids， 7 alkaloids and 16 others， were identified or hypothesized from Lujiao formula， 68 of which were identified by comparison with standard substances. And the results of tissue distribution showed that 100， 143， 129 and 126 prototype components were detected in blood， heart， liver and kidney， respectively. ConclusionThe chemical composition of Lujiao formula and their tissue distribution were systematic analyzed， which can provide reference for the quality control， clinical application， pharmacokinetics and pharmacodynamic material basis of Lujiao formula and its medicinal materials.

A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Impact of Folic Acid on the Resistance of Non-small Cell Lung Cancer Cells to Osimertinib by Regulating Methylation of DUSP1 / 中国肺癌杂志

BACKGROUND@#Drug resistance is the main cause of high mortality of lung cancer. This study was conducted to investigate the effect of folic acid (FA) on the resistance of non-small cell lung cancer (NSCLC) cells to Osimertinib (OSM) by regulating the methylation of dual specificity phosphatase 1 (DUSP1).@*METHODS@#The OSM resistant NSCLC cell line PC9R was establishd by gradually escalation of OSM concentration in PC9 cells. PC9R cells were randomly grouped into Control group, OSM group (5 μmol/L OSM), FA group (600 nmol/L FA), methylation inhibitor decitabine (DAC) group (10 μmol/L DAC), FA+OSM group (600 nmol/L FA+5 μmol/L OSM), and FA+OSM+DAC group (600 nmol/L FA+5 μmol/L OSM+10 μmol/L DAC). CCK-8 method was applied to detect cell proliferation ability. Scratch test was applied to test the ability of cell migration. Transwell assay was applied to detect cell invasion ability. Flow cytometry was applied to measure and analyze the apoptosis rate of cells in each group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) method was applied to detect the expression level of DUSP1 mRNA in cells. Methylation specific PCR (MSP) was applied to detect the methylation status of the DUSP1 promoter region in each group. Western blot was applied to analyze the expression levels of DUSP1 protein and key proteins in the DUSP1 downstream mitogen-activated protein kinase (MAPK) signaling pathway in each group.@*RESULTS@#Compared with the Control group, the cell OD450 values (48 h, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of extracellular regulated protein kinases (ERK) were obviously increased (P<0.05); the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the DAC group were obviously increased (P<0.05); the apoptosis rate, the expression of p38 MAPK protein, the phosphorylation level of ERK, and the methylation level of DUSP1 were obviously reduced (P<0.05). Compared with the OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously increased (P<0.05). Compared with the FA+OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM+DAC group were obviously increased; the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously reduced (P<0.05).@*CONCLUSIONS@#FA may inhibit DUSP1 expression by enhancing DUSP1 methylation, regulate downstream MAPK signal pathway, then promote apoptosis, inhibit cell invasion and metastasis, and ultimately reduce OSM resistance in NSCLC cells.

Analysis of neuropsychological development characteristics and influencing factors in children with speech sound disorder / 中华预防医学杂志

Objective: Exploring the neuropsychological developmental characteristics and influencing factors of children with speech disorder. Methods: A case-control study was conducted. A total of 395 children diagnosed with speech disorders were selected as speech sound disorder (SSD) group from January 2019 to September 2021 in the speech-speech outpatient department of the Children's Hospital Affiliated to Capital Institute of Pediatrics, and 1 179 healthy children who underwent physical examination in the health department during the same period were selected as the control group. All the children were examined by the "Children's Neuropsychological Behavior Scale 2016 Edition" (Children's Mind Scale 2016 edition). Independent sample t test was used to compare the developmental levels of the two groups of children, including total developmental quotient, gross motor, fine motor, adaptive ability, language and social behavior ability. The influential factors of children's speech disorders were analyzed by univariate Chi-square analysis and multivariate logistic regression. Results: There were 395 SSD children, including 296 males and 99 females, 4≤ age ≤6, (4.71±0.76) years. There were 1 179 children in the control group, including 864 males and 315 females, 4≤ age ≤6, (4.64±0.78) years. The mean value of total developmental factors in SSD group was lower than that in control group [(86.45±11.57)/(91.24±8.0), t=-7.78, P<0.01], and the mean values of total developmental markers in both boys and girls in SSD group were lower than those in control group [(86.00±11.40)/(90.78±7.86), t=-6.70, P<0.01; (87.82±12.03)/(92.87±8.49), t=-3.88, P<0.01]. The mean values of gross motor, fine motor, adaptive ability, language ability and social behavior in SSD group were lower than those in control group [(89.76±12.47)/(92.01±10.69), t=-3.21, P<0.01; (80.62±13.64)/(84.49±11.55), t=-5.06, P<0.01; (87.92±15.25)/(92.98±12.06), t=-6.00, P<0.01; (86.48±16.30)/(94.55±12.08), t=-9.04, P<0.01; (87.02±15.18)/(92.63±12.57), t=-6.62, P<0.01]; The mean value of fine motor in boys was lower than that in girls in SSD group [(79.80±13.42)/(83.08±14.05), t=-2.08, P<0.05]. Independent mealtimes. 2 years old (OR=1.527, 95%CI: 1.180-1.977, P=0.001), delay in adding supplemental food (OR=1.510, 95%CI: 1.123-2.029, P=0.006), dialect in the home language environment (OR=1.351, 95%CI: 1.060-1.723, P=0.015) were risk factors for children with speech disorders. Conclusion: Children with speech disorders are more common in boys. The overall development level of SSD children is lower than that of normal children, and the fine motor of SSD boys is lower than that of girls. The incidence of children's speech disorders is related to the addition time of supplementary food, independent meal time and family language environment.

The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro / 中西医结合学报

OBJECTIVE@#JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.@*METHODS@#HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.@*RESULTS@#HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).@*CONCLUSION@#JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.

Mechanisms of copper transporter 1 gene in regulating radiation induced intestinal injury / 中华放射医学与防护杂志

Objective:To investigate the effects and mechanisms of copper transporter 1 (CTR1) in radiation induced intestinal injury in vitro. Methods:Human small intestinal epithelial cells (HIEC) were irradiated with 2, 4, 6, 8 Gy of X-rays and rat intestinal epithelial cells (IEC-6) were irradiated with 5, 10, 15, 20 Gy of X-rays. At 2, 4, 8, 24, and 48 h after irradiation, the expression of CTR1 was detected by Western blot assay. In some experiments, HIEC and IEC-6 cells were transfected with CTR1 shRNA and then exposed to X-rays. Copper levels were detected by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The radiosensitivity of cells was verified by colonogenic assay, the cellular reactive oxygen species (ROS) level and DNA damage were detected to further explore the related mechanism. In addition, Western blot was applied to detect the expressions of antioxidants and cuproptosis associated proteins in enterocytes after silencing CTR1 or irradiation.Results:The expression of CTR1 was increased by X-ray irradiation in a dose-dependent manner ( t=3.53, 3.45, 6.37, 11.11, 11.13, P<0.05). CTR1 expression was successfully diminished by CTR1 shRNA adenovirus vectors. According to the survival curves, the enhancement ratios of the radiosensitivity of HIEC and IEC-6 cells with CTR1 knocking-down were 1.146 and 1.201, respectively. Radiation-induced copper accumulation was alleviated after CTR1 silencing in IEC-6 cells ( t=3.10, P<0.05). At 0.5 h after irradiation, the ROS production in the CTR1 knockdown group was significantly lower than that in the control group ( t=5.23, 2.96, P<0.05). At 1 h after irradiation, the protein expression of γ-H2AX in the CTR1 knockdown group was obviously lower than that in the control group ( t=7.50, 4.29, P<0.05). The expressions of Nrf2 and HO-1 were increased after irradiation, which could be further increased after CTR1 silencing. In addition, cuproptosis associated protein DLAT, LIAS and FDX1 were reduced post-irradiation, which were recovered after CTR1 silencing. Conclusions:The radioresistance of HIEC and IEC-6 cells was enhanced after CTR1 silencing, possibly through the intracellular ROS and cuproptosis pathway.

Efficacy and safety of sofosbuvir-based direct-acting antiviral treatment in children and adolescent patients with chronic hepatitis C / 中华传染病杂志

Objective:To explore the efficacy and safety of sofosbuvir-based direct-acting antiviral treatment in children and adolescent patients with chronic hepatitis C (CHC).Methods:A total of 52 children and adolescent patients who admitted to The Third People′s Hospital of Kunming City and The People′s Hospital of Fuyuan County aged from three to 17 years old with CHC from January 2018 to August 2022 were enrolled, and their basic information was collected. Patients were treated with sofosbuvir/velpatasvir (SOF/VEL) or ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin for 12 weeks. The biochemical and virological indexes were followed up before and after treatment and 12 weeks after withdrawal. The primary endpoint was the sustained virological response (SVR) at week 12 of follow-up after treatment, and the occurrence of adverse events (AE) during treatment. Statistical analysis was used by nonparametric test.Results:A total of 52 patients with CHC including 38 children and 14 adolescents were enrolled. Thirty-one were male and 21 were female. The age was 9(7, 12) years old. Among 52 patients, seven patients were type 1b, 11 were type 2a, three were type 2, five were type 3a, 18 were type 3b, one was type 6a, three were type 6k, four were type 6n and one was type 6v. Twelve (23.1%) patients were vertical transmission, 21(40.4%) patients had horizontal transmission among family members, two (3.8%) patients were blood fluid transmission, and 17(32.7%) were unknown transmission route. Compared with the baseline levels, Total bilirubin, alanine aminotransferase and aspartate aminotransferase were all significantly decreased after 12 weeks of treatment and 12 weeks after withdrawal, and the differences were statistically significant ( F=12.71, 30.23 and 42.52, respectively, all P<0.05). Up to September 30, 2022, 100.0%(52/52) of patients achieved SVR at the end of treatment. For patients who completed follow-up for 12 weeks after treatment, 95.8%(46/48) achieved SVR. Common AEs during treatment were fatigue (11.5%(6/52)), headache (5.8%(3/52)), dizziness (1.9%(1/52)), abdominal pain (3.8%(2/52)), diarrhea (1.9%(1/52)), rash (1.9%(1/52)) and skin pruritus (1.9%(1/52)). No patients discontinued treatment because of AE. Conclusions:Sofosbuvir-based direct-acting antiviral treatment is efficient and well-tolerated in children and adolescent patients with CHC. No patients discontinued treatment due to AE.

Clinical characteristics of patients with acquired immunodeficiency syndrome complicated with nontuberculous mycobacteria disease / 中华传染病杂志

Objective:To explore the clinical characteristics of acquired immunodeficiency syndrome (AIDS) complicated with nontuberculous mycobacteria (NTM) disease.Methods:The clinical data of 190 patients with AIDS complicated with NTM disease diagnosed by Shanghai Public Health Clinical Center, Fudan University from January 1, 2019 to December 31, 2021 were analyzed retrospectively. NTM diseases were divided into disseminated NTM disease group and non-disseminated NTM disease group. The independent sample t test, Mann Whitney U test and chi-square test were used for statistical analysis. Results:The 190 patients with AIDS complicated with NTM disease included 182 males and eight females. The age was (42±13) years old, and the first hospital stay was 15(6, 26) days. Pneumocystis carinii pneumonia was the most common co-infection in 12.1%(23/190) of patients, 87 cases (45.8%) were disseminated NTM disease. The clinical symptoms of patients were common in fever (55.8%(106/190)), cough (50.0%(95/190)), and expectoration (28.9%(55/190)). The proportions of fatigue (31.0%(27/87) vs 7.8%(8/103)), poor appetite (21.8%(19/87) vs 10.7%(11/103)) in the AIDS patients with disseminated NTM disease group were higher than those in the non-disseminated NTM disease group, and the differences were statistically significant ( χ2=16.99, P<0.001 and χ2=4.42, P=0.036, respectively). There was no significant difference in the proportions of deaths between AIDS patients with disseminated NTM disease and those without disseminated NTM disease (17.2%(15/87) vs 12.6%(13/103), χ2=0.80, P=0.371). The most common NTM species was Mycobacterium avium (67.1%(49/190)), followed by Mycobacterium kansasii (15.1%(11/190)). Hemoglobin ((90.3±23.9) g/L vs (110.1±24.2) g/L), albumin ((29.7±5.5) g/L vs (34.7±5.6) g/L), CD4 + T lymphocyte count (11(5, 30)/μL vs 52(16, 96)/μL) and CD8 + T lymphocyte count ((362±320)/μL vs (496±352)/μL) in the disseminated NTM disease group were lower than those in non-disseminated NTM disease group ( t=-5.63, P<0.001; t=-6.18, P<0.001; Z=-5.90, P<0.001; and t=-2.73, P=0.007, respectively), while procalcitonin (0.24(0.10, 0.77) μg/L vs 0.10 (0.04, 0.51) μg/L) was higher than that in the non-disseminated NTM disease group ( Z=-3.09, P=0.002), with statistical significance. The most common imaging features were lung patch and strip shadow (67.4%(128/190)). Conclusions:The most common type of AIDS patients complicated with NTM disease is disseminated NTM disease, and Mycobacterium avium is the most common NTM species. The clinical manifestations (fatigue, anorexia) and laboratory tests (hemoglobin, albumin, procalcitonin, CD4 + T lymphocyte count, CD8 + T lymphocyte count) of AIDS patients with disseminated NTM disease and non-disseminated NTM disease are different, while the prognosis is not significantly different.

Changing trends of the clinical and epidemiological characteristics of acquired immunodeficiency syndrome-associated talaromycosis in Shanghai City / 中华传染病杂志

Objective:To analyze the clinical and epidemiological characteristics and changing trends of acquired immunodeficiency syndrome (AIDS)-associated talaromycosis in Shanghai City.Methods:The clinical data of patients with AIDS-associated talaromycosis hospitalized at Shanghai Public Health Clinical Center, Fudan University from Janauary 1, 2014 to December 31, 2021 were collected. The medical information included age, gender, place of origin, clinical symptoms, imaging manifestations, blood routine test, CD4 + T lymphocyte count. The chi-square test or Fisher exact probability test was used for statistical analysis. Univariate logistic regression was used to analyze the related risk factors for death. Results:From 2014 to 2021, a total of 12 165 AIDS patients were admitted, including 169 (1.4%) AIDS-assiociated talaromycosis patients. The proportions of AIDS-associated talaromycosis in AIDS inpatients from 2014 to 2021 were 1.8%(21/1 149), 1.1%(14/1 307), 1.3%(19/1 446), 0.9%(15/1 610), 1.2%(20/1 626), 1.2%(22/1 778), 1.7%(28/1 624) and 1.8%(30/1 625), respectively, which had not changed much. There was no statistically significant difference in the proportion of AIDS-associated talaromycosis in AIDS inpatients in different years ( χ2=9.50, P=0.218). Among the 169 patients, 157 cases (92.9%) were male, with the age of (37.9±12.2) years, and 35 were from Jiangxi Province, 31 from Shanghai Municipality, 29 from Zhejiang Province, 17 from Anhui Province, 14 from Fujian Province, 11 from Jiangsu Province, eight from Hunan Province, four from Heilongjiang Province, three cases each from Guangxi Zhuang Autonomous Region, Guizhou Province and Henan Province, two cases each from Hubei Province, Shandong Province, Shanxi Province, Yunnan Province and Guangdong Province, and one case from Chongqing Municipality. Patients from non-traditional endemic areas did not find a clear history of living in traditional endemic areas. Of 169 patients, 143(84.6%) cases had fever, 73(43.2%) had respiratory symptoms, and 26(15.4%) had rash during the course of the disease, 147(87.0%) had pulmonary imaging abnormalities, 94(55.6%) were complicated by other pathogens, and 44(26.0%) had hepatosplenomegaly, 137(81.1%) had CD4 + T lymphocyte count <50/μL. Twenty-three patients died, with the total fatality rate of 13.6%. The overall mortality rate showed a downward trend year by year. There was a statistically significant difference in the case fatality rate of AIDS-associated talaromycosis in different years (Fisher exact probability test, P=0.046). The result of univariate logistic regression model showed that patients with platelet count<50×10 9/L had an increased risk of death (odds ratio ( OR)=3.33, 95% confidence interval ( CI) 1.13 to 9.81, P=0.029). Conclusions:The overall change of AIDS-associated talaromycosis inpatients in Shanghai is not significant, while the prevalence rate has increased slightly in recent two years. The case fatality rate is declining year by year. The proportions of patients without a history of living in or traveling to epidemic areas and without rash as the first manifestation are high, and the main clinical manifestation is multi-system damage. Patients with platelet count<50×10 9/L have an increased risk of death.

Evaluation on the effect of teacher simulate standardized patient consultation training in pediatric practical teaching / 中华医学教育探索杂志

Objective:To evaluate the effect of teacher simulate standardized patient (TSSP) consultation training in pediatric practical teaching.Methods:A total of 120 interns from the five-year clinical medicine major of Batch 2015 were randomly divided into experimental group and control group. In the experimental group, 60 interns were trained by TSSP for consultation after admission. After the training, the clinical parents of the children were consulted and the children were physically examined under the guidance of teachers. In the control group, 60 interns were trained according to the same requirements, but TSSP consultation training was not included. At the end of the practice, the performance, operation skills and medical record writing ability of the interns were compared, and the satisfaction of the experimental group was investigated. SPSS 25.0 software was used for t test and chi-square test. Results:The medical record writing results of the experimental group were (96.15±3.00) points, significantly higher than that of the control group [(81.02±3.29) points], and the differences were statistically significant ( t = 26.38; P < 0.001). In the mini-clinical evaluation exercise (Mini-CEX), the scores of medical history collection, communication skills, humanistic care and physical examination were significantly higher than those of the control group ( t= 15.41, 17.67, 15.39 respectively; all P < 0.001). The experimental group had high satisfaction with the teaching method of TSSP consultation training. Conclusion:TSSP consultation training improves the intern medical record writing ability, doctor-patient communication ability, clinical operation ability, stimulates the learning interest of interns, trains the trainee doctors humanistic consciousness, integrates into the ideological and political education, effectively ensures the quality of practical teaching of pediatrics, and obtains recognition from intern, which is worth promoting.

SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity / 药物分析学报

Small ubiquitin-related modifier(SUMOylation)is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload.However,the function of SUMOylation after myocardial infarction(MI)and the molecular details of heart cell responses to SUMO1 deficiency have not been determined.In this study,we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI.However,SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury.Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells.Among cardiomyocytes,SUMO1 deletion increased the Nppa+Nppb+Ankrd1+cardiomyocyte subcluster pro-portion after MI.In addition,the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice.Importantly,SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes.Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium.Mice preinjected with cardiomyocyte-specific AAV-SUMO1,but not the endothelial cell-specific form,and exhibited ameliorated cardiac remodeling following MI.Collectively,our results identified the role of SUMO1 in cardiomyocytes,fibroblasts,and endothelial cells after Ml.These findings provide new insights into SUMO1 involvement in the patho-genesis of MI and reveal novel therapeutic targets.

Progress of PARP inhibitors in targeted therapy of small cell lung cancer / 国际肿瘤学杂志

Small cell lung cancer (SCLC) is a rapidly developing malignant tumor, which is highly heterogeneous and prone to drug resistance, and the prognosis is usually poor. Poly ADP-ribose polymerase (PARP) inhibitors target the DNA damage response pathway, preventing DNA repair, thereby exerting anti-tumor effects. Currently, PARP inhibitors are used as monotherapy or in combination with DNA-damaging agents or immune checkpoint inhibitors in the treatment of SCLC. Although the current research results are limited, it can be seen that PARP inhibitors may be a breakthrough in the targeted therapy of SCLC.

Co-occurrence trend and association study of Internet addiction and depressive symptoms among students in Inner Mongolia Autonomous Region / 中国学校卫生

Objective@#To investigate the prevalence of Internet addiction and depression of students, and to analyze the co-occurrence and trend, so as to provide a theoretical basis for prevention and controlling measures of Internet addiction and depression.@*Methods@#A total of 6 317,7 152,81 808,71 180 and 89 932 students aged 10 to 24 years from 12 leagues (103 banners) in Inner Mongolia Autonomous Region were selected by stratified random cluster sampling in September each year from 2017 to 2021. The Internet Addiction Scale and the Central for Epidemiologic Studies Depression Scale(CES-D) was used to measure Internet addiction and depression. And the annual inspection rate, group difference and annual change trend in students were calculated. Multivariate linear regression and restricted cubic spline analysis were used to estimate the linear and non linear associations between Internet addiction and depression in students.@*Results@#The Internet addiction proportion in students gradually decreased from 4.1% in 2017 to 2.1% in 2020, but increased to 3.9% in 2021. And the depressive symptoms proportion increased from 20.9% in 2017 to 28.0% in 2020 and 27.0% in 2021. The detection rate of Internet addiction and depression comorbidities remained at 1.8% to 2.5 %. The Internet addiction proportion in boys was higher than that in girls( χ 2=42.82， P <0.05). The depressive symptoms prevalence in girls was higher than that in boys( χ 2= 553.90， P <0.05). Taking reversal in prevalence of Internet addiction in urban and rural areas was observed in 2019. The detection rates of depressive symptoms and comorbidity were higher in urban areas than these in suburban counties on the whole, and the difference showed a trend of decreasing or even equalizing year by year. Internet addiction was positively correlated with depressive symptoms score ( B=1.67, 95%CI =1.64-1.71), the proportion of depressive symptoms ( OR=1.39, 95%CI =1.38-1.41) and the proportion of major depressive symptoms ( OR=1.35, 95%CI =1.33-1.36) among students in 2021 ( P <0.05). An N-shaped curve was found in the significant nonlinear associations between internet addiction and depression across sex, region and school stage.@*Conclusion@#Internet addiction and depression in students show significant linear and non-linear associations, which are consistent in different sexes, regions and school stages. Therefore, relevant measures should be made and implemented in each region, especially in suburb areas, so as to prevent the increasingly development of adolescents and children s Internet addiction and depression.

Effect of LncRNA GAPLINC on the Cell Proliferation of Rheumatoid Arthritis Fibroblast-like Synoviocytes / 中山大学学报(医学科学版)

ObjectiveTo investigate the effect of LncRNA GAPLINC on the cell proliferation of RA-FLSs. MethodsRA-FLSs were cultured from synovial specimens. The expression of LncRNA GAPLINC in RA-FLSs and trauma-FLSs groups was detected by qRCR. GAPLINC suppression was transfected by siRNA and the inhibition efficiency was detected by qRCR. Flow cytometry was adopted to determine the change of cell growth and cell cycle distribution. 【ResμLts】 The expression of LncRNA GAPLINC was significantly higher in RA-FLSs than that of the trauma-FLSs （P<0.05）.Transfection of GAPLINC-siRNA significantly decreased the expression of LncRNA GAPLINC. GAPLINC silence in RA-FLSs revealed significant inhibition in cell proliferation which was showed by the reduced cell number in S phase（P<0.05）. Moreover， flow cytometry assay showed GAPIINC-siRNA treatment group had an accumμLation of cells in the G0/G1 phase and decreased RA-FLSs in the S and G2/M phase（P<0.05）. After GAPLINC knockdown， mRNA and protein levels of Cyclin D1 and PCNA， which were positively correlated with proliferative phenotype， were decreased （P<0.05）， while p21， which was negatively correlated with proliferative phenotype， was up-regμLated （P<0.05）. ConclusionsThe mRNA expression of GAPLINC was higher in RA-FLSs compared with trauma-FLSs ，which was statistically significant（P<0.05）. The silence of LncRNA GAPLINC coμLd significantly inhibit RA-FLSs cell growth and suppress the cell cycle transformation， which suggests that GAPLINC may play a role in the regμLation of proliferation of RA-FLSs， leading to synovial hyperplasia and contributing to RA progression.

Dietary patterns and type 2 diabetes: A cohort study / 中华内分泌代谢杂志

Objective:To explore the association between dietary patterns and the incidence of type 2 diabetes mellitus(T2DM), so as to provide insights for the prevention and management of T2DM.Methods:Participants were recruited from the " The Tianjin Chronic Inflammation and Health Cohort Study(TCLSIH)" cohort study from 2013 to 2018, who had completed the modified semiquantitative food frequency questionnaire(FFQ) and blood glucose testing( n=26 425), free of cardiovascular disease, cancer, or diabetes at baseline. The relevant information collected includes food frequency, blood glucose concentration, and other confounding factors. In this study, the correlation between dietary patterns and T2DM was tested using Cox proportional risk regression model, and the gender stratification analysis and body mass index stratification analysis of different gender groups were carried out. All statistical analysis was performed using SAS 9.3 software. Results:The age of all participants was (41.0±11.5)years, and the cumulative incidence was 3.84% for T2DM. The cumulative incidence of T2DM in male population was 5.29%, while that in female population was 2.16%. There were significant differences in the incidence of T2DM among different genders( P <0.001). The multivariable-adjusted hazard ratios( HR) and corresponding 95% CI of T2DM across the plant-based dietary pattern score were 1.09(95% CI 0.91-1.31), 0.80(95% CI 0.66-0.97), and 0.76(95% CI 0.62-0.94; Ptrend =0.010). Moreover, no statistically significant differences were observed between animal and traditional northern Chinese diets with the incidence of T2DM. Conclusions:The plant-based dietary patterns were associated with substantially lower risk of developing T2DM, and there were no significant association between animal and traditional northern Chinese dietary patterns with T2DM. Plant-based dietary patterns characterized by a variety of fruit, leeks, onions, seaweed may be beneficial to the prevention and control of T2DM.