Effects of moxibustion on serum levels of β-EP, SP and expression of IL-1β and COX-2 protein in brainstem in rats with migraine / 中国针灸

OBJECTIVE@#To observe the effects of moxibustion at "Baihui" (GV 20) and "Dazhui" (GV 14) at different time points on the serum level of β-endorphin (β-EP), substance P (SP) and expression of interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) protein in brainstem in rats with migraine, and to explore the effect and mechanism of moxibustion in preventing and treating migraine.@*METHODS@#Forty male SD rats were randomly divided into a blank group, a model group, a prevention+treatment (PT) group and a treatment group, 10 rats in each group. Except the blank group, the rats in the remaining groups were injected with nitroglycerin subcutaneously to prepare migraine model. The rats in the PT group were treated with moxibustion 7 days before modeling (once a day) and 30 min after modeling, while the rats in the treatment group were treated with moxibustion 30 min after modeling. The "Baihui" (GV 20) and "Dazhui" (GV 14) were taken for 30 minutes each time. The behavioral scores in each group were observed before and after modeling. After intervention, ELISA method was used to detect the serum level of β-EP and SP; the immunohistochemistry method was used to detect the number of positive cells of IL-1β in brainstem; the Western blot method was used to detect the expression of COX-2 protein in brainstem.@*RESULTS@#Compared with the blank group, the behavioral scores in the model group were increased 0-30 min, 60-90 min and 90-120 min after modeling (P<0.01); compared with the model group, in the treatment group and the PT group, the behavioral scores were decreased 60-90 min and 90-120 min after modeling (P<0.01). Compared with the blank group, in the model group, the serum level of β-EP was decreased (P<0.01), while the serum level of SP, the number of positive cells of IL-1β in brainstem and the expression of COX-2 protein were increased (P<0.01). Compared with the model group, in the PT group and and the treatment group, the serum level of β-EP was increased (P<0.01), while the serum level of SP, the number of positive cells of IL-1β and the expression of COX-2 protein in brainstem were decreased (P<0.01, P<0.05). Compared with the treatment group, in the PT group, the serum level of β-EP was increased and COX-2 protein expression was decreased (P<0.05).@*CONCLUSION@#Moxibustion could effectively relieve migraine. The mechanism may be related to reduce the serum level of SP, IL-1β and COX-2 protein expression in brainstem, and increase the serum level of β-EP, and the optimal effect is observed in the PT group.

Effect of acupuncture on swallowing function for patients of Parkinson's disease with dysphagia / 中国针灸

OBJECTIVE@#To observe the effects of acupuncture on swallowing function and quality of life for patients with dysphagia in Parkinson's disease (PD).@*METHODS@#A total of 60 patients of PD with dysphagia were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 3 cases dropped off). The control group was given conventional medication therapy and rehabilitation training. On the basis of the treatment as the control group, the observation group was given acupuncture at Fengfu (GV 16), Baihui (GV 20), Shenting (GV 24), Yintang (GV 24+), Yansanzhen and bilateral Fengchi (GB 20), 30 min each time, once a day, 6 times a week for 4 weeks. Before and after treatment, the Kubota water swallowing test, standardized swallowing assessment (SSA) and swallowing quality of life (SWAL-QOL) were used to evaluate the swallowing function and quality of life of the two groups.@*RESULTS@#After treatment, the Kubota water swallowing test grade, SSA scores in the two groups were decreased compared with those before treatment (P<0.05, P<0.001)，the SWAL-QOL scores were increased compared with those before treatment (P<0.001); in the observation group，the Kubota water swallowing test grade and SSA score were lower than those in the control group (P<0.05)，the SWAL-QOL score was higher than that in the control group (P<0.001).@*CONCLUSION@#On the basis of conventional medication therapy and rehabilitation training，acupuncture could improve the swallowing function and quality of life for patients of PD with dysphagia.

Association between perfluoroalkyl and polyfluoroalkyl substances and maternal thyroid-related hormones in pregnant women / 环境与职业医学

Background Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS) during pregnancy might affect thyroid-related hormone levels in pregnant women. However, most previous studies focused on the effects of PFAS containing 8-10 carbon atoms, and few studies have estimated the associations between PFAS with longer carbon chain and thyroid-related hormone levels. Objective To examine the associations between PFAS exposure and thyroid-related hormones in pregnant women. Methods The present study was based on the Jiashan Birth Cohort from September 2016 to April 2018. We analyzed 13 PFAS in maternal blood samples (n=781) by high-performance liquid chromatography-tandem mass spectrometry, as well as total triiodothyronine (T3), total thyroxine (T4), free T3 (FT3), free T4 (FT4), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), and thyroid peroxidase antibody (TPOAb) by electrochemiluminescence immunoassay. PFAS were divided into three groups:low concentration, medium concentration and high concentration according to the tertile of their concentrations. We estimated the associations between PFAS concentrations and thyroid-related hormones in pregnant women by multiple linear regression. Results In the multiple linear regression models, a change in perfluorododecanoic acid (PFDoA) concentrations from the low concentration group to the high concentration group was associated with a −0.10 (95%CI: −0.20, 0) nmol·L−1 change in T3, −0.15 (95%CI: −0.28, −0.02) pmol·L−1 change in FT3, and −3.02 (95%CI: −5.66, −0.39) pmol·L−1 change in FT4, respectively. A change in perfluorotridecanoic acid (PFTrDA) concentrations from the low concentration group to the high concentration group was associated with a −0.10 (95%CI: −0.20, 0) nmol·L−1 change in T3. Compared with the low concentration group, the concentration of T4 in the medium concentration group of perfluorohexane sulfonate (PFHxS) increased by 6.10 (95%CI: 0.44, 11.75) nmol·L−1. No statistically significant associations were found between PFAS and TSH concentration. The negative associations of PFAS with thyroid-related hormones were more pronounced in pregnant women with positive TG-Ab and/or TPOAb. Conclusion Exposure to PFAS during pregnancy may affect thyroid-related hormone homeostasis in pregnant women, and the effect is stronger in TG-Ab and/or TPOAb-positive pregnant women.

Neonatal nonketotic hyperglycinemia: a case report and literature review / 中国新生儿科杂志

Objective:To study the phenotypes and genotypes of neonatal nonketotic hyperglycinemia (NKH).Methods:A neonate with severe NKH admitted to our hospital was retrospectively analyzed. Using keywords 'glycine cleavage enzyme', 'glycine decarboxylase', 'nonketotic hyperglycinemia' and 'glycine encephalopathy' (both in Chinese and English), multiple medical databases were searched until December 31, 2022. The clinical phenotypes and genotypes of neonatal NKH were summarized.Results:For our case, the neonate was lethargy and had no appetite on the second day of life, followed by recurrent seizures and irregular breathing, requiring mechanical ventilation. She died at 3 weeks of age. Two compound heterozygous variants were found in GLDC gene from whole exome sequencing , one was c.848C>G(p.A283G) of maternal origin and one was c.1607G>A(p.R536Q) of paternal origin. The former was a novel mutation. A total of 54 cases (including this case) were collected. The main clinical manifestations included poor feeding, decreased muscle tone, hiccups, progressive lethargy, irregular breathing, apnea and neonatal seizures. 42 cases (77.8%) had GLDC gene mutations, 9 cases (16.7%) had AMT gene mutations, 2 cases (3.7%) had LIAS gene mutations and 1 case (1.9%) had GCSH gene mutations. Conclusions:Neurological manifestations are most common in neonatal NKH with wide clinical variations. GLDC gene mutations are the predominant pathogenic mutations.

Heat-sensitive moxibustion for migraine without aura: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect between heat-sensitive moxibustion and mild moxibustion for migraine without aura.@*METHODS@#A total of 54 patients with migraine without aura were randomized into an observation group (27 cases, 2 cases dropped off) and a control group (27 cases, 2 cases dropped off). The basic western medication treatment was adopted in the two groups. In the control group, mild moxibustion was applied at Shuaigu (GB 8), Fengchi (GB 20) and Yanglingquan (GB 34) on the affected side. In the observation group, the frequent acupoint areas of the affected side i.e. Shuaigu (GB 8), Fengchi (GB 20), Taiyang (EX-HN 5), Taichong (LR 3), Yanglingquan (GB 34) were determined, 3 acupoints with strong heat-sensitive sensation were selected each time and mild moxibustion was adopted. The treatment was given once a day, 5 times of treatment was as one course and 2 courses were required in the two groups. Before and after treatment, the scores of migraine symptom, visual analogue scale (VAS), migraine specific quality of life questionnaire (MSQ) were observed, and the clinical efficacy was evaluated after treatment in the two groups.@*RESULTS@#After treatment, the scores of migraine symptom and VAS were decreased compared with those before treatment (P<0.01), while the MSQ scores were increased compared with those before treatment (P<0.01) in the two groups. After treatment, the scores of migraine symptom and VAS in the observation group were lower than those in the control group (P<0.05), while the MSQ score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 92.0% (23/25) in the observation group, which was superior to 72.0% (18/25) in the control group (P<0.05).@*CONCLUSION@#Both heat-sensitive moxibustion and mild moxibustion can effectively alleviate the clinical symptoms, improve the headache degree and life quality in patients with migraine without aura, the clinical efficacy of heat-sensitive moxibustion is superior to that of mild moxibustion.

The molecular mechanism of Qizhu anti-cancer prescription in treatment of primary liver cancer based on network pharmacology and experimental verification / 中国药理学通报

Aim To investigate the mechanism of Qizhu anti-cancer prescription ( QZACP) inthe treatment of primary liver cancer using network pharmacology and molecular docking. Methods Drugs and primary liver cancer ( PLC) -related targets were found according to TCMSP database and disease databases such as GeneCard, the key chemical components and core targets were screened by Cytoscape 3. 9. 1 and String platform respectively, and a network relationship diagram of traditional Chinese medicine-active component-target was constructed by using Cytoscape 3.9. 1. GO functional analysis and KEGG pathway analysis were performed using DAVID platform, visualized by R 4. 1. 1 software, and finally the core clustered proteins were analyzed by CytoNCA plug-in to obtain the core action targets, and the core components and key targets were verified by using molecular docking technology and the pharmacodynamic mechanism of QZACP was further verified by animal experiments. Results The active ingredients of QZACP in the treatment of primary liver cancer may be quercetin, glycyrrhizin, Denudatin B, isoflavanone, sanguinarol, etc. ; the potential targets were STAT3, EGFR, AKT1 etc. ; the related pathways were mainly PI3K-Akt signaling pathway,MAPK signaling pathway,etc. ; molecular docking showed that the core compounds had better integrating conformation with the key targets. In addition, QZACP could inhibit the growth of tumor in nude mice and decrease the expression of STAT3, EGFR and AKT1. Conclusions Qizhu anti-cancer prescription may have some positive significance in the treatment of primary liver cancer, which may be related to the regulation of PI3K/Akt signaling pathway.

Clinical characteristics and short-term prognosis of 22 cases with SARS-CoV-2 infection associated acute encephalopathy / 中华儿科杂志

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

Comparison between laparoscopic-assisted natural orifice specimen extraction surgery and conventional laparoscopic surgery for left colorectal cancer: a randomized controlled study with 3-year follow-up results / 中华胃肠外科杂志

Objective: To evaluate the mid-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using the Cai tube in the treatment of left colorectal cancer. Methods: A prospective randomized control trial (China Clinical Trials Registration Number: ChiCTR-OOR-15007060) was performed. Sixty patients with left colorectal cancer at Department of Gastrointestinal Surgery of Zhongshan Hospital from September 2015 to August 2017 were prospectively enrolled. Case inclusion criteria: (1) left colorectal adenocarcinoma (rectal cancer with distance ≥ 8 cm from tumor low margin to anal edge, sigmoid colon cancer, descending colon cancer and left transverse colon cancer) confirmed by preoperative pathology; (2) satisfactory conditions of conventional laparoscopic surgery; (3) maximum diameter of the tumor < 4.5 cm confirmed by preoperative abdominal and pelvic CT or MRI; (4) BMI < 30 kg/m2. Case exclusion criteria: (1) benign lesions, mucinous adenocarcinoma, signet-ring cell carcinoma and other special pathological types of tumors confirmed by preoperative pathological examination; (2) multiple or recurrent cancers; (3) with a history of neoadjuvant chemoradiotherapy; (4) obvious regional infiltration or distant metastasis indicated by preoperative imaging examination; (5) intestinal obstruction, intestinal perforation, etc. Participants were randomly assigned to NOSES group (using the Cai tube) and conventional laparoscopy (CL) group by random number table method. Clinical data between two groups were compared and analyzed, including perioperative conditions, tumor exfoliation cell detection and bacterial culture results of intraperitoneal lavage fluid, postoperative complications (Clavien-Dindo grading), postoperative pain [visual simulation scoring (VAS) assessment], anal function (Kirwan anal function grading assessment), and postoperative 3-year disease-free survival (DFS), overall survival (OS), overall recurrence rate, and local recurrence rate. Results: A total of 60 patients were enrolled, with 30 in the NOSES group and 30 in the CL group. All the patients in the NOSES group successfully completed operation with Cai tube. Baseline data between the two groups were not significantly different (all P>0.05). There were no statistically significant differences between two groups in conversion rate to open surgery, number of lymph node harivested, proximal and distal resection margin of tumor, negative rate of circumferential margin, operation time, blood loss, inflammatory indexes, postoperative anal function, postoperative hospital stay, hospitalization cost, morbidity of postoperative complications (Clavien-Dindo grade II or above) (all P>0.05). Compared to the CL group, the NOSES group had lower maximum postoperative VAS score (2.5±0.3 vs. 5.1±0.4, t=3.187, P<0.01), and fewer use of additional postoperative analgesia [6.7% (2/30) vs. 33.3% (10/30),χ2=6.670, P=0.02]. The postoperative time to gas passage was shorter in the NOSES group [(2.2±1.4) days vs. (3.1±1.2) days,P=0.026]. No tumor cells and bacterial contamination were found in abdominal lavage fluid before and after operation in either group. The anal function at postoperative 3-month of all the patients in the NOSES group was Kirwan grade I to II, while in the CL group, anal function of 2 cases (6.7%) was Kirwan grade III, and of 28 cases was also Kirwan grade I to II, whose difference was not statistically significant (P>0.05). In the NOSES group and the CL group, 3-year DFS was 96.7% and 83.3% (P=0.090), OS was 100% and 90% (P=0.096), overall recurrence rate was 3.3% and 10.0% (P=0.166), and local recurrence rate was 3.3% and 3.3% (P=0.999), respectively, whose differences were not statistically significant (all P>0.05). Conclusions: In the treatment of left colorectal cancer, compared with conventional laparoscopic colectomy, NOSES colectomy using Cai tube exhibits less scar, less postoperative pain, shorter recovery of gastrointestinal function, and similar mid-term outcomes. Given proper surgical indications, the surgical procedure is safe and feasible.

Ultrasonographic features and clinical pathological of liver metastasis in patients with melanoma / 中华肿瘤杂志

Objective: To investigate the ultrasonographic features and clinical pathological of liver metastasis in patients with melanoma. Methods: Thirteen patients with liver metastasis from melanoma treated in Tianjin Medical University Cancer Institute and Hospital from 2013 to 2019 were selected, and their ultrasonographic and clinicopathological characteristics were analyzed retrospectively. Results: Eleven of the 13 patients had multiple liver lesions. The maximum diameter of the lesions was (5.89±2.73) cm. Five cases of lesions were mixed echo (3 cases with high melanin content), 4 cases of lesions were hyperechoic (3 cases with low melanin content), 3 cases of lesions were hypoechoic (all with high melanin content), 1 case of lesions were equal echo (with high melanin content). The lesions in 11 patients had clear boundaries, while other 2 patients lacked the clear borders. Cystic areas were present in the lesions of 3 patients. Six cases had irregular lesions (lobulated), and 7 cases had regular lesions (round, oval). There were acoustic halos around the lesion in 9 cases and smooth and uneven acoustic halos in 5 cases. The results of immunohistochemistry showed that 11 cases were positive for S-100, HMB45 and Melan-A. One patient was not tested for HMB45, while S-100 and Melan-A were positive. One patient did not undergo Melan-A test, while S-100 and HMB45 were positive. Conclusion: Most of the liver metastases of melanoma are mixed echo or hyperechoic, most of them are nodular with clear boundaries combined with vocal halo, and a few of the lesions have cystic areas.

Carrier-free nanoparticles based on self-assembly of active ingredients from Chinese medicine / 药学学报

Traditional Chinese medicine has a long history, unique system and perfect technology, which has been used to prevent or treat a variety of diseases in the form of compound medicine. Recently, some of the active ingredients from Chinese medicine were found to have self-assembly properties, mainly through non-covalent interactions, including π-π stacking, electrostatic interaction, hydrogen bond and coordination interactions, etc. Carrier-free nanoparticles based on self-assembly of active ingredients from Chinese medicine could not only improve the solubility of insoluble active ingredients, but also the bioavailability. As nanocarriers, the natural active ingredients could exert synergistic therapeutic effects. The strategy of self-assembly without carrier is safer and almost non-toxic compared to the commonly used nanocarriers. In addition, some ingredients from Chinese medicine could coordinate with metal ions to form stable nanoparticles, which could be applied to photothermal therapy. In this paper, we summarized and analyzed the recent achievements of carrier-free nanoparticles based on self-assembly of active ingredients from Chinese medicine, and briefly outlined the future development of this kind of nanomedicine.

Research progress of glucagon receptor related compounds / 药学学报

Type 2 diabetes is a complex metabolic disease, accompanied by insulin resistance and elevated blood glucose. As the disease progresses, hyperglucagonemia will occur. Glucagon has a significant effect on glucose increase and energy expenditure. In recent years, several glucagon receptor (GCGR) antagonists were developed. They lowered blood glucose in clinical studies, along with side effects, such as increased blood lipids and elevated liver transaminase. In order to solve these problems, glucagon like peptide 1 receptor (GLP-1R)/GCGR co-agonists were developed, which not only lower blood glucose, but also reduce weight and promote lipolysis. In this review, we will focus on the biological effects of glucagon, the treatments of GCGR antagonists, and GLP-1R/GCGR co-agonists on type 2 diabetes.

Predicting the number of visceral leishmaniasis cases in Kashgar, Xinjiang, China using the ARIMA-EGARCH model

Objective: To forecast the visceral leishmaniasis cases using autoregress integrated moving average (ARIMA) and hybrid ARIMA-EGARCH model, which offers a scientific basis to control visceral leishmaniasis spread in Kashgar Prefecture of Xinjiang, China. Methods: The data used in this paper are monthly visceral leishmaniasis cases in the Kashgar Prefecture of Xinjiang from 2004 to 2016. The sample data between 2004 and 2015 were used for the estimation to choose the best model and the sample data in 2016 were used for the forecast. Time series of visceral leishmaniasis started on 1 January 2004 and ended on 31 December 2016, consisting of 1 790 observations reported in Kashgar Prefecture. Results: For Xinjiang, the total number of reported cases were 2 187, the male-to-female ratio of cases was 1:1.42. Patients aged between 0 and 10 years accounted for 82.72% of all reported cases and the largest percentage of visceral leishmaniasis cases was detected among scattered children who accounted for 68.82%. The monthly incidences fitted by ARIMA (2, 1, 2) (1, 1, 1)

Advances in molecular mechanisms for enhanced hepatic lipogenesis in insulin resistance / 药学学报

Hepatic selective insulin resistance refers to that insulin fails to suppress hepatic glucose production but continues to promote hepatic lipogenesis in insulin resistance. Therefore, type 2 diabetes mellitus is characterized with dyslipidemia apart from hyperglycemia. This review highlights the roles and molecular mechanisms of the key hepatic lipogenesis factors such as sterol regulatory factor binding protein 1c (SREBP1c), mammalian rapamycin target complex 1 (mTORC1), endoplasmic reticulum stress (ER stress), FoxO1, lipid synthesis substrate, etc.

Role of microglial pyroptosis in hypoxic-ischemic brain damage / 中国当代儿科杂志

OBJECTIVE@#To investigate the role of microglial pyroptosis in hypoxic-ischemic brain damage.@*METHODS@#An oxygen-glucose deprivation/reoxygenation (OGD/R) model of rat microglial cells were cultured in vitro. Western blot was used to measure the expression of the pyroptosis-related proteins caspase-1, interleukin-1β (IL-1β), and N-terminal gasdermin D (GSDMD-N) at 0, 1, 3, 6, 12, and 24 hours after OGD/R. After the microglial cells were transfected with lentivirus-mediated silenced gasdermin D (GSDMD), immunofluorescence assay and Western blot were used to measure the transfection rate of GSDMD. Microglial cell lines were divided into three groups: normal control, negative control, and LV-sh_GSDMD (lentivirus-mediated GSDMD silencing). CCK-8 assay and LDH kit were used to observe the effect of GSDMD silencing on the viability and toxicity of microglial cells at 24 hours after OGD/R. Western blot was used to observe the effect of GSDMD silencing on the levels of caspase-1, GSDMD-N, and IL-1β in the microglial cells at 24 hours after OGD/R.@*RESULTS@#The expression levels of the pyroptosis-related proteins caspase-1, GSDMD-N, and IL-1β in microglial cells were upregulated since 0 hour after OGD/R and reached the peak levels at 24 hours. A microglial cell model of lentivirus-mediated GSDMD silencing was successfully constructed. At 24 hours after OGD/R, compared with the normal control group, the GSDMD silencing group had a significant increase in the cell viability and a significant reduction in the cytotoxicity (P<0.05), as well as significant reductions in the protein expression levels of caspase-1, GSDMD-N, and IL-1β in microglial cells (P<0.05).@*CONCLUSIONS@#Lentivirus silencing of the key substrate protein for pyroptosis GSDMD can alleviate hypoxic-ischemic brain damage, suggesting that microglial pyroptosis aggravates hypoxic-ischemic brain damage.

Application of D2-40/CD34-CK cocktail antibodies for colorectal cancer with insufficient lymph node harvest / 临床与实验病理学杂志

Purpose To investigate the value of application of D2-40/CD34-CK cocktail antibodies by double immunohistochemical staining for assessment of lymphovascular invasion (LVI) and to determine its prognostic significance in colorectal cancer with insufficient lymph node harvest. Methods Specimens from 133 cases of colorectal cancer with less than 12 lymph nodes were selected. HE staining and double immunohistochemical staining of the cocktail antibodies were performed to compare the difference of the two methods in screening for LVI. The The relationship between LVI confirmed by cocktail antibody immunohistochemical staining and clinicopathological characteristics and overall survival (OS) of patients was analyzed. Results (1) The detection rates of cocktail antibody double immunohistochemical staining and HE staining for LVI were 42.9％ (57/133) and 21.8％ (29/133) with statistically significant difference (P < 0.001). (2) The presence of LVI confirmed by double staining was significantly associated with Dukes staging, depth of invasion, clinical stages, lymph node metastasis and tumor budding (P < 0.05). (3) The presence of LVI, the location and extent of LVI, and the number of tumor cells in thrombus ≥5.5 for cases with LVI ≤2 clusters, were significantly associated with OS (P < 0.05). Conclusion D2-40/CD34-CK cocktail antibodies double staining is superior to routine HE staining in assessing LVI. LVI is intimately associated with tumor stage, lymph nodes metastasis and tumor budding, and it is an independent prognostic factor for CRC patients. It should be a supplementary examination for these patients with insufficient lymph node harvest.

Distribution of HIV subtypes in HIV/AIDS patients in Guizhou from 2013 to 2017 / 中华疾病控制杂志

Objective To investigate the molecular characteristics of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients receiving antiretroviral therapy (ART) in Guizhou Province. Methods Using a convenience sampling strategy, 8 583 samples were collected in Guizhou and an investigation was conducted including face-to-face questionnaire interview and HIV testing. Results 1 511 cases failed in HIV suppression (viral load, VL>1 000 copies/ml). 1 410 cases (93.31%) were successfully genotyped with HIV pol gene, among which 51.42% were genotyped as CRF01_AE, 26.67% as CRF07_BC and 16.1% as CRF08_BC. Conclusion The subtype changes caused by HIV gene mutation should precede the changes of main transmission routes of HIV through the analysis in recent years. Timely monitoring the changes of HIV subtypes can be one of the main bases for the prevention and control of AIDS.

Prognostic Values of Serum Chloride and Sodium Levels in Patients with Three-vessel Disease / 生物医学与环境科学（英文）

OBJECTIVE@#Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD.@*METHODS@#We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients.@*RESULTS@#A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score.@*CONCLUSION@#Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.

Comparison of Long-term Outcomes in Patients with Premature Triple-vessel Coronary Disease Undergoing Three Different Treatment Strategies: A Prospective Cohort Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Patients with premature triple-vessel disease (PTVD) have a higher risk of recurrent coronary events and repeat revascularization; however, the long-term outcome of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and medical therapy (MT) alone for PTVD patients is controversial. The aim of this study is to evaluate the long-term outcome of PTVD patients among these three treatment strategies, to find out the most appropriate treatment methods for these patients.</p><p><b>METHODS</b>One thousand seven hundred and ninety-two patients with PTVD (age: men ≤50 years and women ≤60 years) were enrolled between 2004 and 2011. The primary end point was all-cause death. The secondary end points were cardiac death, myocardial infarction, stroke, or repeat revascularization.</p><p><b>RESULTS</b>PCI, CABG, and MT alone were performed in 933 (52.1%), 459 (25.6%), and 400 (22.3%) patients. Both PCI and CABG were associated with lower all-cause death (4.6% vs. 4.1% vs. 15.5%, respectively, P < 0.01) and cardiac death (2.8% vs. 2.0% vs. 9.8%, respectively, P < 0.01) versus MT alone. The rate of repeat revascularization in the CABG group was significantly lower than those in the PCI and MT groups. After adjusting for baseline factors, PCI and CABG were still associated with similar lower risk of all-cause death and cardiac death versus MT alone (all-cause death: hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.23-0.53, P < 0.01 and HR: 0.35, 95% CI: 0.18-0.70, P = 0.003, respectively, and cardiac death: HR: 0.32, 95% CI: 0.19-0.54, P < 0.01 and HR: 0.36, 95% CI: 0.14-0.93, P = 0.03, respectively).</p><p><b>CONCLUSIONS</b>PCI and CABG provided equal long-term benefits for all-cause death and cardiac death for PTVD patients. Patients undergoing MT alone had the worst long-term clinical outcomes.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov; Identifier: NCT02634086. https://www.clinicaltrials.gov/ct2/show/record/NCT02634086?term=NCT02634086&rank=1.</p>

Injection of botulinum-A toxin into bulbospongiosus muscle for primary premature ejaculation: A preliminary clinical study / 中华男科学杂志

<p><b>Objective</b>To evaluate the efficacy and safety of injection of botulinum-A toxin into the bulbospongiosus muscle in the treatment of primary premature ejaculation (PPE).</p><p><b>METHODS</b>According to the inclusion criteria, we randomly assigned 70 outpatients with PPE to a trial and a control group of equal number, the former injected with 100 U botulinum-A toxin at 10 U/ml and the latter with the same volume of saline into the bulbospongiosus muscle. Then, we obtained the intravaginal ejaculatory latency time (IELT), scores of the Premature Ejaculation Profile (PEP), Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD), and Hospital Anxiety and Depression Scale (HADS), and the incidence of adverse reactions between the two groups before and 4 weeks after treatment.</p><p><b>RESULTS</b>Complete data were obtained from 69 of the patients, 34 in the trial and 35 in the control group. The effectiveness rate was 47.06% (16/34) in the former but 0 in the latter. At 4 weeks after treatment, the patients of the trial group showed a significantly longer IELT than the controls and the baseline (［2.35 ± 1.83］ vs ［0.79 ± 0.21］ and ［0.74 ±+ 0.27］ min, P < 0.01) and the controls. The patients in the trial group, in comparison with those in the saline control group and the baseline, also exhibited significant improvement in the scores of PEP-ejaculation control (1.21 ± 1.04 vs 0.49 ± 0.56 and 0.47 ± 0.51, P < 0.05), PEP-sexual satisfaction (1.32 ± 1.01 vs 0.71 ± 0.57 and 0.79 ± 0.48, P < 0.05), PEP-PE-related distress (2.12 ± 1.01 vs 2.80 ± 0.68 and 2.76 ± 1.26, P < 0.05), and PEP-PE-induced difficult relationship with the partners (1.38 ± 0.70 vs 2.37 ± 0.55 and 2.12 ± 1.49, P < 0.05). The sexual satisfaction score of the female partners after treatment was markedly improved in the trial group as compared with the control group and the baseline (1.18 ± 1.00 vs 0.57 ± 0.50 and 0.62 ± 0.60, P < 0.05). There were no statistically significant differences in MSHQ-EjD and HADS scores between the two groups before and after treatment. Adverse reactions were observed in 6 cases (17.65%) in the trial group, including 4 cases of decreased erectile hardness (11.76%) and 2 cases of incomplete urination (5.88%), which occurred from the 3 to 4 days after injection, and those with decreased erectile hardness could complete sexual intercourse without any other treatment and recovered after 3 weeks.</p><p><b>CONCLUSIONS</b>Injection of botulinum-A toxin into the bulbospongiosus muscle can be used as an option for the treatment of PPE. Its clinical application value, however, needs to be verified by further studies with larger samples.</p>

Clinical study on the changes of plasma melatonin and stress factors in neonatal asphyxia / 临床儿科杂志

Objective To explore the changes in plasma melatonin (MT) and glucocorticoid (GC) and the expressions of melatonin receptor 1 (MR1) and glucocorticoid receptor alpha (GR alpha) after neonatal asphyxia. Methods Full-term asphyxia neonates (22 cases of mild asphyxia, 28 cases of severe asphyxia) hospitalized from May 2014 to December 2015 were selected. Another 50 non-asphyxiated full-term newborns hospitalized with single disease such as infection and jaundice at the same time were selected as the control group. Peripheral blood samples were collected within 24 hours after birth and 7 days after birth, and plasma and mononuclear cells were separated. The plasma MT and GC expression levels were detected by ELISA. Real-time PCR was used to detect MR1 and GRα mRNA expression. Results The plasma GC concentrations in mild and severe asphyxia group increased significantly within 24 hours after birth, higher than that in control group. In addition, the plasma GC concentration in severe asphyxia group was significantly higher than that in mild group (P<0.05). The concentration of plasma GC in mild and severe asphyxia group decreased on the 7th day after birth (P<0.05) and was significantly lower than that at 24 hours after birth, but it was still higher in the severe asphyxia group than that in mild group; both the mild and severe asphyxia group had higher GC level than that in control group; the differences are statistically significant (P<0.05). Within 24 hours after birth, the plasma MT concentration in severe asphyxia group was lower than that in mild asphyxia group and control group, and there were significant differences (P<0.05). Compared with 24 hours after birth, the concentrations of plasma MT in severe and mild asphyxia groups increased significantly, higher than that in control group on the 7th day, and there were significant differences (P<0.05). The level of GR alpha mRNA expression decreased within 24 hours after birth in severe asphyxia group, but was increased in the mild asphyxia group, and there were significant differences among the three groups (P<0.05). The expression levels of GRα in both mild and severe asphyxia groups recovered on the 7th days after birth, and there were no significant differences compared with control group (P>0.05). Compared with 24 hours after birth , the expression level of MR1 mRNA in severe asphyxia group increased on the 7th day after birth, higher than that in control group and in mild asphyxia group, and there were significant differences (P<0.05). Conclusions The stress caused by severe asphyxia exceeds the adaptation range in the newborn, and results in the high expressions of MR1 and endogenous MT.