UPLC-Q-Orbitrap-MS based metabolomics and analysis of the effect of Suanzaoren Decoction on serum of chronic unpredictable mild stress depression rats / 药学学报

A UPLC-Q-Orbitrap-MS based metabolomic approach combined with biochemical assay and histopathological inspection were employed to study the intervention effects of Suanzaoren Decoction (SZRD) on chronic unpredictable mild stress (CUMS) depression rats, and to clarify the metabolic regulation pathway of SZRD. The rats were randomly divided into normal control group, CUMS model group, positive drug venlafaxine group, SZRD high (24 g·kg-1) and low (12 g·kg-1) dose groups, respectively. The CUMS model was replicated by subjecting to a variety of stimulus, such as thermal stimulation, ice water swimming, ultrasonic stimulation, tail clamping, day and night reversal, plantar electric shock and so on for rats. After oral administration of drugs for 28 days, the behavioral indexes of rats in each group were observed and the hippocampus and serum samples of rats were collected for biochemical assay and histopathological inspection. Compared with the CUMS model group, low dose and high dose SZRD groups can significantly reduce the immobility time of forced swimming (P < 0.001, P < 0.001), increase the sucrose preference rate (P < 0.01, P < 0.05), the number of crossings (P < 0.05, P < 0.01) and the number of uprights (P < 0.05, P < 0.01) in the open field test, suggesting that SZRD can significantly improve the depression-like behavior of CUMS model rats. In addition, SZRD could significantly reduce the levels of serum IL-6, IL-1β and TNF-α of CUMS model rats. A total of 21 differential metabolites in serum were identified by comparison with the data from the literature and databases. In addition, low-dose SZRD and high-dose SZRD improved the 8 and 11 perturbed potential serum biomarkers that were induced by CUMS, respectively, which related to alanine, aspartic acid and glutamic acid, tryptophan and arachidonic acid metabolism. This study provides a scientific basis for expanding the clinical indications of SZRD. This experiment was approved by the Animal Ethics Committee of Shanxi University (Approval No. SXULL2020028).

Treatment duration of wrist-ankle acupuncture for relieving post-thyroidectomy pain: A randomized controlled trial / 中西医结合学报

BACKGROUND@#Treatment duration of wrist-ankle acupuncture (WAA) is uncertain for post-thyroidectomy pain relief.@*OBJECTIVE@#This study evaluated the effect of different WAA treatment duration on post-operative pain relief and other discomforts associated with thyroidectomy.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This randomized controlled trial was conducted at a single research site in Guangzhou, China. A total of 132 patients receiving thyroidectomy were randomly divided into the control group (sham WAA, 30 min) and three intervention groups (group 1: WAA, 30 min; group 2: WAA, 45 min; group 3: WAA, 60 min), with group allocation ratio of 1:1:1:1. Acupuncture was administered within 1 hour of leaving the operating room.@*OUTCOMES AND MEASURES@#Primary outcome was patients' pain at the surgical site assessed by visual analogue scale (VAS) at the moment after acupuncture treatment (post-intervention). Secondary outcomes included the patients' pain VAS scores at 6, 12, 24, 48 and 72 h after the thyroidectomy, the 40-item Quality of Recovery (QoR-40) score, the grade of post-operative nausea and vomiting (PONV), and the use of additional analgesic therapy.@*RESULTS@#The adjusted mean difference (AMD) in VAS scores from baseline to post-intervention in group 1 was -0.89 (95% confidence interval [CI], -1.02 to -0.76). The decrease in VAS score at post-intervention was statistically significant in group 1 compared to the control group (AMD, -0.43; 95% CI, -0.58 to -0.28; P < 0.001), and in groups 2 and 3 compared to group 1 (group 2 vs group 1: AMD, -0.65; 95% CI, -0.81 to -0.48; P < 0.001; group 3 vs group 1: AMD, -0.66; 95% CI, -0.86 to -0.47; P < 0.001). The VAS scores in the four groups converged beyond 24 h after the operation. Fewer patients in group 2 and group 3 experienced PONV in the first 24 h after operation. No statistical differences were measured in QoR-40 score and the number of patients with additional analgesic therapy.@*CONCLUSION@#Compared with the 30 min intervention, WAA treatment with longer needle retention time (45 or 60 min) had an advantage in pain relief within 6 h after surgery. WAA's analgesic effect lasted for 6-12 h post-operatively. Please cite this article as: Han XR, Yue W, Chen HC, He W, Luo JH, Chen SX, Liu N, Yang M. Treatment duration of wrist-ankle acupuncture for relieving post-thyroidectomy pain: A randomized controlled trial. J Integr Med. 2023; 21(2): 168-175.

Mutations of PTCH1 gene in two pedigrees with bifid rib-basal cell nevus-jaw cyst syndrome / 浙江大学学报·医学版

Two male patients with bifid rib-basal cell nevus-jaw cyst syndrome (BCNS) were admitted to Department of Stomatology, the First Affiliated Hospital of Bengbu Medical College due to radiological findings of multiple low density shadows in the jaw. Clinical and imaging findings showed thoracic malformation, calcification of the tentorium cerebellum and falx cerebrum as well as widening of the orbital distance. Whole exon high-throughput sequencing was performed in two patients and their family members. The heterozygous mutations of c.C2541C>A(p.Y847X) and c.C1501C>T(p.Q501X) in PTCH1 gene were detected in both patients. Diagnosis of BCNS was confirmed. The heterozygous mutations of PTCH1 gene locus were also found in the mothers of the two probands. Proband 1 showed clinical manifestations of low intelligence, and heterozygous mutations of c.C2141T(p.P714L) and c.G3343A(p.V1115I) were detected in FANCD2 gene. Proband 2 had normal intelligence and no FANCD2 mutation. The fenestration decompression and curettage of jaw cyst were performed in both patients. Regular follow-up showed good bone growth at the original lesion, and no recurrence has been observed so far.

Erianin inhibits oral cancer cell growth, migration, and invasion via the Nrf2/HO-1/ GPX4 pathway

Objective: To evaluate the effect of erianin on the viability, migration, and invasion of KB cells and elucidate its underlying mechanisms. Methods: Cell Counting Kit-8, colony formation, wound healing, and Transwell assays were used to determine the proliferation, migration, and invasion of oral cancer KB cells. Furthermore, malondialdehyde (MDA) and glutathione (GSH) levels were determined. Fluorescent probes were used to detect changes in intracellular reactive oxygen species and iron ions. Additionally, the expressions of ferroptosis-related proteins, NF-E2-related factor 2 (Nrf2), ferritin heavy chain 1 (FTH1), heme oxygenase 1 (HO-1), and glutathione peroxidase 4 (GPX4) were analyzed by Western blotting assays. Results: Erianin induced ferroptosis and inhibited the proliferation, migration, and invasion of KB cells. Moreover, erianin decreased GSH level, increased MDA level, elevated intracellular ROS and Fe

Genetic analysis of a Chinese pedigree affected with branchiootic syndrome due to a nonsense variant of EYA1 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic basis for a Chinese pedigree suspected for branchiootic syndrome (BOS).@*METHODS@#The proband was subjected to target-capture high-throughput sequencing to detect potential variant of deafness-associated genes. Candidate variants were verified by Sanger sequencing of the family members.@*RESULTS@#The proband was found to harbor a c.1627C>T (p.Gln543Ter) nonsense variant of the EYA1 gene. Sanger sequencing confirmed that all of the 4 patients with the BOS phenotype from the pedigree have harbored the same heterozygous variant. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PS+PP3+PP4).@*CONCLUSION@#The c.1627C>T (p.Gln543Ter) variant of the EYA1 gene probably underlay the BOS phenotype in this pedigree. Above finding has provided a basis for its clinical diagnosis.

PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Evaluation of CT value with dual-energy CT in predicting cerebral hemorrhagic transformation after endovascular treatment in patients with acute ischemic stroke / 中华神经科杂志

Objective:To evaluate the value of dual-energy CT (DECT) mixed images CT in predicting hemorrhagic transformation (HT) after endovascular therapy (EVT) of acute ischemic stroke (AIS).Methods:From October 2018 to January 2020, the immediate dual-energy CT images of intracranial high attenuation (HA) regions in patients with AIS after endovascular treatment in Wuhan No.1 Hospital were retrospectively analyzed. According to the diagnostic criteria of CT or diffusion weighted image in 72 hours of follow-up, they were classified into HT group and non-HT group. The CT value of mixed images, contrast media, and virtual non-enhancement (VNC) and iodine concentration in the highest attenuation areas were measured. Intragroup correlation coefficient was used to evaluate the consistency among the readers; Mann-Whitney U test was used to compare the difference between the two groups of quantitative parameters; Spearman correlation analysis was uesd for evaluating correlation between mixed images CT value and contrast media CT value, VNC CT value, and iodine concentration. The receiver operating characteristic curve was used to analyze the quantitative parameters to predict the diagnostic efficacy of HT. Results:A total of 154 cases were enrolled, with 65 cases in the HT group and 89 cases in the non-HT group. The intraclass correlation coefficient of CT values of mixed images was 0.861 ( P<0.05). Comparing the non-HT group and the HT group,the CT value of mixed images [59.40(54.84, 63.05) HU vs 100.10(79.90, 122.40) HU, Z=-10.87, P<0.001],contrast agent CT value [24.90(20.75, 30.05) HU vs 66.60(47.10, 84.15) HU, Z=-10.85, P<0.001] and iodine concentration [1.10(1.00, 1.30) mg/ml vs 2.90(2.05, 3.65) mg/ml, Z=-10.85, P<0.001] both increased in the HT group, but there was no significant difference in VNC CT values between the two groups [33.60(31.80, 35.70) HU vs 34.30(30.90, 38.00) HU, Z=-0.50, P=0.62]. There was a highly significant correlation between the CT value of mixed images and iodine concentration ( r=0.99, P<0.01). Using CT value>72.60 HU as the diagnostic cutoff value for predicting HT, the sensitivity and specificity were 89.23% and 95.51%, respectively. Conclusions:The CT value of DECT mixed images after EVT can be used to predict HT within 72 hours. When DECT was not available, conventional CT scan′s intracranial HA density over 72.60 HU can be selected as the cutoff value for predicting HT.

Dietary intake and nutritional status of children with autism spectrum disorders in Tianjin / 中国学校卫生

Objective@#To investigate the dietary nutrient intake and nutritional status of children with autism spectrum disorder(ASD), and provide evidence for developing scientific and effective nutrition intervention measures for children with ASD.@*Methods@#Nutrient intake of 90 children with ASD were investigated by using 3 day 24 hour dietary survey, and the anthropological indexes were measured.@*Results@#Among the 90 ASD children aged 3-9, 31 of them were overweight and obese, accounting for 34.4%, three children were underweight, accounting for 3.3%, and one child was stunted, accounting for 1.1%. Dietary intakes of vitamin A, vitamin B 1, vitamin D, vitamin B 6, folic acid, calcium and iodine in all age groups of ASD children were insufficient, but the dietary intakes of copper, phosphorus and zinc exceeded the recommended intake level. More than 10% of the ASD children consume copper and magnesium more than the tolerable upper intake level. There were significant differences in the dietary intake of energy, fat and vitamin A among normal, overweight, obese and thin ASD children( χ 2=9.24, 10.03, P <0.05).@*Conclusion@#Overweight and obesity, as well as the combination of insufficient and excessive nutrition in children with ASD is common. Personalized dietary nutrition intervention towards ASD children should be developed and implemented.

Role of dendritic cells in host immunity to herpes simplex virus and possible mechanisms / 中华微生物学和免疫学杂志

Herpes simplex virus (HSV) is a double-stranded DNA virus that can infect skin and mucosal epithelial cells. It can establish latency in sensory neurons and sporadically reactivate from these cells. In order to reply to attacks of the host and evade the immunity surveillance during infection and reactivation, HSV has developed a multitude of clever strategies. Dendritic cells (DCs), one of the most important antigen-presenting cells (APC), can recognize pathogens at the infection sites and activate specific T cells, thus playing a crucial role in the host immunity against virus infection. This paper reviewed the mechanism of the host immunity against HSV, especially the role of DCs in HSV-induced immune responses and the future research perspective.

Iron deficiency and early childhood caries: a systematic review and meta-analysis / 中华医学杂志(英文版)

BACKGROUNDS@#Previous surveys have found that children with iron deficiency (ID) were likely to suffer from early childhood caries (ECC). We aimed to assess the scientific evidence about whether ID is intrinsically related to ECC.@*METHODS@#The medical subject headings (MeSH) terms and free words were searched on PubMed, Web of Science, Cochrane, China National Knowledge Infrastructure, Wanfang, and the Database for Chinese Technical Periodicals from March 2020 to September 2020. Two researchers independently screened the articles. Data extraction and cross-checking were performed for the studies that met the inclusion criteria. Meta-analysis was performed using the Cochrane Collaboration's Review Manager 5.3 software.@*RESULTS@#After excluding duplication and irrelevant literature, 12 case-control studies were included in the study. The meta-analysis demonstrated that children with ECC were more likely to have ID (odds ratio [OR] = 2.63, 95% confidence interval [CI]: [1.85, 3.73], P < 0.001). There was no statistically significant association found between the level of serum ferritin and ECC (weighted mean difference (WMD) = -5.80, 95% CI: [-11.97, 0.37], P = 0.07). Children with ECC were more likely to have iron-deficiency anemia (OR = 2.74, 95% CI: [2.41,3.11], P < 0.001). The hemoglobin (HGB) levels in the ECC group were significantly lower compared with that in the ECC-free group (WMD = -9.96, 95% CI: [-15.45, -4.46], P = 0.0004). The mean corpuscular volume (MCV) levels in the ECC group were significantly lower compared with that in the ECC-free group (WMD = -3.72, 95% CI: [-6.65, -0.79], P = 0.01).@*CONCLUSIONS@#ID was more prevalent in children with ECC, and the markers of iron status in the ECC group, such as serum ferritin, HGB, and MCV, were relatively lower than the ECC-free group.

Tripterygium wilfordii in Treatment of Kidney Diseases and Its Toxic and Side Effect： A Review / 中国实验方剂学杂志

In recent years， with the rapid development of traditional Chinese medicine industry in China， the efficacy of Chinese medicinals in treating disease and maintaining health has been increasingly recognized. Tripterygium wilfordii， a Chinese medicinal for expelling wind， dredging collaterals， removing dampness， and relieving pain， is commonly used for treating acute and chronic glomerulonephritis， rheumatoid arthritis， and other diseases. However， the frequent occurrence of adverse reactions has limited its wide application in clinical practice. The existing studies have gradually confirmed that T. wilfordii and its active ingredients exert the bidirectional effects on kidney function. This paper reviewed the related clinical applications and articles published in the past decades and summarized the material basis for its bidirectional effects and the specific action mechanisms in renal protection and renal damage. It was found that the main active ingredients in T. wilfordii were tripterygium glycosides and triptolide， which exerted the protective or toxic and side effects on kidney by regulating immunity， influencing mitogen-activated protein kinases （MAPK） pathway， and changing the expression and function of renal transporters. Besides， the roles of administration time， dosage， and body status in the exertion of protective or toxic and side effects by T. wilfordii were also discussed. The review aimed to provide new ideas for the research on the treatment of kidney diseases with T. wilfordii and its safety application.

Clinical characteristics and biochemical parameters of diabetic nephropathy patients / 公共卫生与预防医学

Objective To study the clinical characteristics and biochemical parameters of diabetic nephropathy patients , and to understand the occurrence of chronic complications such as kidney diseases. Methods From February 1, 2017 to November 30, 2020, 352 patients with type 2 diabetes aged between 35 and 70 years with diabetes lasting more than 10 years were selected for study. According to the estimated glomerular filtration rate (EGFR), the patients were divided into two groups, in which the patients with EGRF were less than 15mL/min/1.73m2, and they suffered from ESRD and underwent hemodialysis. The subjects in the second group were reclassified into three groups according to their urinary albumin excretion, including microalbuminuria, massive albuminuria and end-stage renal disease (ESRD). To analyze the hematological and biochemical parameters in different stages of diabetic nephropathy. Results Among 232 patients with nephropathy, 96 cases (41.38%) had microalbuminuria, 43 cases (18.53%) had albuminuria and 91 cases (39.22%) had end-stage renal disease (ESRD).The remaining 120 patients (34.09%) did not develop nephropathy. Patients with kidney disease are older, with an average age (SD) of 55.62 6.00 years, and diabetes lasts longer (19.04 6.33 years). The BMI of patients with kidney disease is lower than that of patients without kidney disease. Among them, insulin resistance, elevated uric acid level, low red blood cell count and low hemoglobin level are related to the significantly increased risk of albuminuria and ESRD. Elevated levels of uric acid and LDH are associated with significantly increased risk of microalbuminuria and ESRD, while elevated red blood cell distribution width is associated with significantly increased risk of ESRD. Conclusion Diabetic nephropathy is related to insulin resistance, changes of liver enzymes and uric acid, as well as abnormal red blood cell count and red blood cell shape, which need to be monitored frequently by diabetic nephropathy patients.

Myeloid-Derived Suppressor Cells Recruited by Chemokine (C-C Motif) Ligand 3 Promote the Progression of Breast Cancer via Phosphoinositide 3-Kinase-Protein Kinase B-Mammalian Target of Rapamycin Signaling / 한국유방암학회지

Purpose@#Numerous studies have shown that the frequency of myeloid-derived suppressor cells (MDSCs) is associated with tumor progression, metastasis, and recurrence. Chemokine (C-C motif) ligand 3 (CCL3) may be secreted by tumor cells and attract MDSCs into the tumor microenvironment. In the present study, we aimed to explore the molecular mechanisms whereby CCL3 is involved in the interaction of breast cancer cells and MDSCs. @*Methods@#The expression of CCL3 and its receptors was investigated using real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The cell counting Kit-8, wound healing, and transwell assays were performed to study cell growth, migration, and invasion. Cell cycling, apoptosis, and the frequency of MDSCs were investigated through flow cytometry. Transwell assays were used for co-culture and chemotaxis detection. Markers of the epithelial-mesenchymal transition (EMT) were determined with western blotting. The role of CCL3 in vivo was studied via tumor xenograft experiments. @*Results@#CCL3 promoted cell proliferation, migration, invasion, and cycling, and inhibited apoptosis of breast cancer cells in vitro. Blocking CCL3 in vivo inhibited tumor growth and metastases. The frequency of MDSCs in patients with breast cancer was higher than that in healthy donors. Additionally, MDSCs might be recruited by CCL3. Co-culture with MDSCs activated the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin (PI3K-Akt-mTOR) pathway and promoted the EMT in breast cancer cells, and their proliferation, migration, and invasion significantly increased. These changes were not observed when breast cancer cells with CCL3 knockdown were co-cultured with MDSCs. @*Conclusion@#CCL3 promoted the growth of breast cancer cells, and MDSCs recruited by CCL3 interacted with these cells and then activated the PI3K-Akt-mTOR pathway, which led to EMT and promoted the migration and invasion of the cells.

Evaluation of Residual Stepping Ability in Monkeys with Spinal Cord Injury / 中国康复理论与实践

Objective:To evaluate the residual stepping ability in monkeys with spinal cord injury longitudinally. Methods:Four adult female monkeys were studied. Right hemisection of 10 mm spinal cord tissue was performed at the T7-9 segment. Gait tests of bipedal locomotion were performed before, and six weeks and twelve weeks after injury by VICON system. Gait cycle duration, amplitude of knee and ankle angles, and ratio of united parameters were obtained from successive stepping and were quantitative analyzed. Results:The coordination of bilateral hindlimbs was destroyed after spinal cord injury, and the right hindlimb showed obviously dragging. The gait cycle duration of the left hindlimb increased significantly (P < 0.001), and the amplitudes of knee and ankle angle significantly increased (P < 0.001) after spinal cord injury. The ratio of united parameters was not statistically different among all the time points (P > 0.05). The gait cycle duration of the left hindlimb was correlated with step length (r = 0.838, P = 0.001), step height (r = 0.726, P = 0.007) and amplitude of ankle angle (r = 0.766, P = 0.004), and the amplitude of ankle angle was correlated with step length (r = 0.627, P = 0.029). Conclusion:The gait pattern of monkey with spinal cord injury has been changed. The gait strategy of the uninjured side was adjusted compensatively after spinal cord injury to adapt the functional impairment of contralateral hindlimb.

Characteristic and clinical significance of microRNA expression between 144 Uygur and Han women with endometrial carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To compare the expression patterns of microRNA (miRNA) between 144 Uygur and Han women with endometrial carcinoma and to investigate their clinical significance.@*METHODS@#Taqman miRNA low-density array was used to compare miRNA profiles between Uygur and Han women with non-endometrioid endometrial carcinoma (NEEC). Five miRNAs were further analyzed in the 144 endometrial cancers including 62 Uygur and 82 Han samples via real-time PCR to determine their expression patterns.@*RESULTS@#MiRNA expression profiles revealed that many miRNAs overexpressed or downregula-ted in one ethnic group, but did not express or changed slightly in the other ethnic group. Further detection in the 144 endometrial cancers showed that miR-141, miR-200a, and miR-205 overexpressed in both ethnic groups. In Uygur endometrioid endometrial carcinoma (EEC), tumors with miR-141/200a overexpression tended to be more aggressive in behavior, whereas in the Han group, EEC with miR-200a overexpression was relative mild. However, the NEEC with miR-200a overexpression also had aggressive clinicopathologic features in the Han women. MiR-145 and miR-143 expressed differentially between Uygur and Han groups, they overexpressed in the former and decreased in the latter (P<0.05). In the Uygur women miR-145/143 increased significantly in NEEC and there was a trend that NEEC exhibiting favorable clinicopathologic factors had higher miR-145 expression, and was statistically significant in tumors with myometrial invasion less than 1/2 thickness (P=0.042). By contrary, miR-145/143 decreased in Han group and EEC with worse clinicopathologic variables had lower expression although without statistical significance. NEEC in Han group had no such tendency.@*CONCLUSION@#Uygur and Han women might have different miRNA expression profiles. MiR-141/200a/205 overexpressed in endometrial carcinomas and miR-141/200a might behave differently between these two ethnic groups as well as in EEC and in NEEC. Although miR-145/143 showed inverse expression patterns between Uygur and Han women with endometrial cancer, they all exerted tumor suppression effect on endometrial cancer.

A correlation study of CT and clinical features of different clinical types of COVID-19 / 中华放射学杂志

Objective:To investigate the CT and clinical features of COVID-19.Methods:Chest CT and clinical data of 103 patients who were confirmed as COVID-19 in January 2020 were collected retrospectively. According to diagnosis and treatment of COVID-19 (trial version 5), all the patients were classified into common( n=58), severe ( n=36) and critical ( n=9) types, and their clinical findings, laboratory examination and CT finding were analyzed. CT features included distribution, location, size, shape, edge, number and density of the lesion, percentage of pneumonia lesions of the whole lung and extra-pulmonary manifestations. The CT features among different clinical types were compared using χ 2 test or Fisher's exact probability. Comparisons of age, duration from onset to CT examination, and percentage of pneumonic lesions to total lung volume among different types were performed by using analysis of variance (normal distribution) or Kruskal-Wallis rank sum test (non-normal distribution). Results:In terms of clinical manifestations, the patients with critical COVID-19 were more common in elderly men, with a median age of 65 years. Fever was the first symptom in 49 (84%) of 58 common patients, and also the first symptom in both severe and critical COVID-19 patients. The incidence of coughing in severe (25/36, 69%) and critical (6/9, 67%) COVID-19 patients was higher than that in common patients (20/58, 34%). All critical patients had dyspnea. CT showed the common COVID-19 was located in bilateral lung (40/58, 71%)with multiple (40/58, 69%), ground glass (31/58, 52%) or mixed (25/58, 43%)opacities (56/58, 97%), while all the severe and critical COVID-19 were located in bilateral lung(100%) with multiple (34/36, 96%), patchy (33 /36, 92%), or mixed opacities (26/36, 72%) in severe patients, and with mixed opacities more than 3 cm in critical patients. As for the percentage of pneumonia focus in the whole lung volume, the common type (12.5%±6.1%) was significantly lower than the severe type (25.9%± 10.7%) and the critical type (47.2%±19.2%), with statistically significant differences( P< 0.001 and 0.002 respectively), and the severe type COVID-19 was also significantly lower than the critical type ( P= 0.032). Conclusions:CT and clinical features of different clinical types of COVID-19 pneumonia are different. Chest CT findings are characteristic, which can not only help the early diagnosis but also evaluate the clinical course and severity.

Metformin: one of the possible options to reduce the mortality of severe coronavirus disease 2019? / 中华危重病急救医学

According to the world epidemic report, the mortality of patients with severe coronavirus disease 2019 (COVID-19) is high. Diabetic patients are more susceptible to COVID-19. Since the mortality of COVID-19 patients with diabetes is on the top of list, hyperglycemia is considered an independent risk factor for severe COVID-19. Up to now, there is few effective treatment for severe patients infected with 2019 novel coronavirus (2019-nCoV). Clinical studies observed that cytokine storms existed in patients with severe COVID-19. Sustained high levels of cytokines cause diffuse damage to pulmonary capillary endothelial cells and alveolar epithelial cells, resulting in acute respiratory distress syndrome (ARDS). ARDS is the main cause of death in COVID-19 patients. Host-directed therapy (HDT) is an emerging therapeutic method in the field of anti-infection, which can activate the self-protective immune response, suppress excessive inflammatory response, and be used to assist the treatment of traditional drugs to shorten the course of disease. Metformin has been shown to be effective in HDT and can assist in the treatment of the viral and bacterial infectious disease. This paper discusses the rationality and potential therapeutic mechanism of metformin in the treatment of severe COVID-19. It was speculated that the use of metformin for controlling blood glucose in severe COVID-19 patients with diabetes may prevent or inhibit the occurrence of ARDS, thereby reducing the mortality of COVID-19 patients. The possible mechanism is that metformin could inhibit cytokine storm via suppressing interleukin-6 (IL-6) signaling, prevent the process of lung fibrosis, suppress endocytosis, thereby elevating angiotensin converting enzyme 2 (ACE2) expression.

Study on clinical and genetic characteristics of PCDH19 gene mutation related epilepsy / 中华实用儿科临床杂志

Objective:To retrospectively analyze the clinical and genetic features of PCDH19 gene mutation related epilepsy in 11 families. Methods:The clinical manifestations and genetic mutation characteristics of 13 children (from 11 families) diagnosed with PCDH19 gene mutation related epilepsy at the Department of Pediatric Neurology, the Third Affiliated Hospital of Zhengzhou University from March 2013 to July 2019 were analyzed. Results:(1) The results of PCDH19 gene mutations: among 11 probands, 10 children had point mutations of PCDH19 gene and one child was with Exon 5 deletion.One male patient was detected with mosaic PCDH19 mutation, which was c. 840C > A, and the proportion of variation was 34.27%.Five hereditary and 6 de novo mutations were identified in 11 probands.Three patients inherited mutations from their clinically asymptomatic fathers with hemizygous mutation.Two patients inherited from their mothers, 1 case was diagnosed with epilepsy and the other was asymptomatic carrier.(2) Clinical features: there were 12 females and 1 male in the enrolled 13 children, with the age of onset of less than 2 years old.The clinical phenotypes: epilepsy with mental retardation in 9 patients, which including 3 patients with Dravet syndrome, and the remaining 4 patients were epilepsy without mental retardation.The phenotypic heterogeneity was observed in females with identical mutations from the same family, and a few girls can be asymptomatic.In all patients, seizures in clusters were observed in all 13 cases, fever sensitivity in 12 cases, and status epilepticus was only found in 3 cases.Of all the patients, only 2 cases had no seizures for more than 2 years, 3 cases with Dravet syndrome were given 6 to 8 kinds of antiepileptic drugs successively, but there were still frequent seizures. Conclusions:Most patients with PCDH19 mutations-related epilepsy are females, while rare mosaic males can be affected, phenotypic heterogeneity is obvious.Seizures in clusters and fever sensitivity are the major clinical features, and most patients are companied with different levels of intellectual impairment.Mutations in PCDH19 can be inherited or de novo, most of which are point mutations.

A correlation study ofCT and clinical features of different clinical types of 2019 novel coronavirus pneumonia / 中华放射学杂志

Objective@#To investigate the CT and clinical features of 2019 novel coronavirus (NCP) pneumonia.@*Methods@#Chest CT and clinical data of confirmed 103 patients with 2019 novel coronavirus pneumonia in January 2020, retrospectively. According to diagnosis and treatment of NCP infected pneumonia (trial version 5), all the patients were classified into mild(n=58), severe (n=36) and very severe (n=9) type, and their clinical findings, laboratory examination and CT finding were analyzed. CT features included lesions’ distribution, location, size, shape, edge, number, density, percentage of pneumonia lesions of the whole lung and extra-pulmonary manifestations. The CT features of different clinical subtypes were compared using χ2test or Fisher's exact probability. Comparisons between the percentage of pneumonic lesions to total lung volume were computed by using analysis of variance (normal distribution) or Kruskal-Wallis rank sum test (non-normal distribution).@*Results@#In terms of clinical manifestations, the patients with severe NCP were more common in elderly men, with a median age of 65 years. Fever was the first symptom in 49 (84%) of 58 patients with NCP, and fever was the first symptom in both severe and critical NCP patients. The incidence of cough in severe (25 / 36, 69%) and critical (6 /9, 67%) NCP patients was higher than that in general (20 /58, 34%). All critical patients have dyspnea. In terms of CT findings, common NCP showed double lung (40/58,71%) multiple (40 / 58,69%) ground glass (31/58,52%) or mixed (25 / 58,43%) lesions (56 / 58,97%); severe and critical NCP showed double lung lesions, heavy NCP mainly showed multiple (34 / 36,96%) patches (33 / 36,92%) mixed density lesions (26 / 36,72%); 9 severe NCP lesions were more than 3 cm Mixed density lesions. The percentage of pneumonia focus in the whole lung volume: the common type (12.5% ± 6.1%) was significantly lower than the severe type (25.9% ± 10.7%) and the critical type (47.2% ± 19.2%) NCP, the difference was statistically significant (P values were < 0.001 and 0.002 respectively), and the severe type NCP was also significantly lower than the critical type (P = 0.032).@*Conclusions@#CT and clinical features of different clinical types of NCP pneumonia are different. Chest CT findings have unique characteristic, which can not only make early diagnosis, but also evaluate its clinical course and severity.

Investigating Relationship Between Renal Damage and Endoplasmic Reticulum Stress in Diabetic Kidney Disease Rats with Blood Stasis Syndrome Based on Combination of Disease and Syndrome / 中国实验方剂学杂志

Objective:To observe the effect of blood stasis syndrome on renal damage and endoplasmic reticulum stress (ERS) in diabetic kidney disease (DKD) rats, and to explore the relationship between renal syndrome of blood stasis damage and ERS in DKD rats. Method:The 50 Male SD rats of SPF level were selected to establish DKD rat model by high fat and high sugar diet combined with intra-abdominal injection of streptozotocin(STZ). They were randomly divided into normal group, diabetes mellitus group and diabetes mellitus and blood stasis syndrome group（0.05 mg·kg-1）, among which diabetes mellitus and blood stasis syndrome group was prepared by dextran method. The general conditions, hemorheology indexes, 24 h urine protein, serum creatinine and renal pathology of the rats in each group were observed. Immunohistochemical analysis, Western blot and Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR)were used to detect mRNA and protein expressions of endoplasmic reticulum stress-related proteins glucose regulated protein 78(GRP78), activating transcription factor-6(ATF6) and renal fibrosis index fibronectin(FN), and alpha smooth muscle actin(α-SMA). Result:Compared with normal group, the rats in diabetes mellitus group showed polyphagia, polyuria and weight loss, increased hemorheology index of whole blood viscosity and plasma viscosity(P<0.05，P<0.01), increased 24 h urine protein, serum creatinine and urea nitrogen(P<0.01), and increased renal pathology, and increased mRNA and protein expression of GRP78, ATF6, FN and α-SMA(P<0.05，P<0.01). After dextran preparation of blood stasis model. Diabetes mellitus and blood stasis syndrome group increased mortality, signs of change is more obvious in the diabetic group, whole blood viscosity, plasma viscosity, 24 h urine protein ration, serum creatinine and urea nitrogen were significantly higher than those in diabetic rats(P<0.01), pathological changes aggravated in the diabetes group. At the same time， mRNA and protein expressions of GRP78, ATF6, FN, and α-SMA in renal tissue were significantly higher than those in diabetic mellitus group(P<0.05，P<0.01). Conclusion:Under the combined disease and syndrome model, the blood stasis syndrome may further aggravate the pathological damage of the kidney of DKD rats, and is related to the enhancement of ERS in the kidney of DKD rats.