1.Clinical trial of semaglutide and saxagliptin combined with metformin in the treatment of patients with type 2 diabetes mellitus with abdominal obesity
Yong-Ju LIU ; Rui LI ; Na-Na HAO ; Wan-Wan LI
The Chinese Journal of Clinical Pharmacology 2024;40(10):1400-1404
Objective To observe the effects and safety of semaglutide and saxagliptin combined with metformin in the treatment of type 2 diabetes mellitus(T2DM)with abdominal obesity(AO).Methods The data of patients with T2DM and AO were retrospectively analyzed.Patients with T2DM and AO were divided into semaglutide group and saxagliptin group according to the cohort method.Both groups were given metformin orally,0.5 g a time,tid.On this basis,the semaglutide group was injected with semaglutide,0.25 mg a time,2 weeks later,the dose was adjusted to 0.5 mg a time,qw.The saxagliptin group was given oral administration of saxagliptin on the basis of metformin,5 mg a time,qd.All patients received 3 months of treatment.Glucose metabolism indexes,pancreatic islet function indexes,adipokines and adverse drug reactions were compared between the groups.Results There were 48 cases in semaglutide group and 49 cases in saxagliptin group.After treatment,the levels of fasting plasma glucose(FPG)in the semaglutide group and the saxagliptin group were(7.45±1.22)and(7.98±1.30)mmol·L-1;the levels of 2 h plasma glucose(2 h PG)were(9.78±1.64)and(10.55±1.82)mmol·L-1;the levels of hemoglobin A1c(HbA1c)were(5.66±0.94)and(6.25±0.87)%;the levels of fasting insulin(FINS)were(29.12±2.46)and(34.34±7.15)pmol·L-1;the levels of fasting C-peptide(FC-P)were(292.66±67.53)and(319.03±77.92)pmol·L-1;homeostatic model assessment-insulin resistance(HOMA-IR)were 2.51±0.78 and 2.94±0.89;homeostatic model assessment-β(HOMA-β)were 51.74±15.31 and 43.72±14.56;levels of Irisin were(4.56±0.32)and(4.17±0.54)ng·L-1;the levels of spexin(SPX)were(0.71±0.15)and(0.64±0.17)ng·mL-1;the levels of asprosin(ASP)were(1.22±0.16)and(1.34±0.25)μg·L-1.The above indexes were significantly different between semaglutide group and saxagliptin group(all P<0.05).The total incidence rates of adverse drug reactions in semaglutide group and saxagliptin group were 10.42%(5 cases/48 cases)and 2.04%(1 case/49 cases),without statistically significant difference(P>0.05).Conclusion The combination of semaglutide and metformin can lower blood glucose and in patients with T2DM and AO more significantly,and improve pancreatic function and adipokines,with good safety.
2.Single-cell transcriptomic sequencing coupled with Mendelian randomization analysis elucidates the pivotal role of CTSC in chronic rhinosinusitis
Shican ZHOU ; Ju LAI ; Kai FAN ; Jingwen LI ; Xiayue XU ; Chunyan YAO ; Bojin LONG ; Chuanliang ZHAO ; Na CHE ; Yawen GAO ; Shaoqing YU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(6):551-559
Objective:To investigate the molecular mechanisms of chronic rhinosinusitis (CRS), to identify key cell subgroups and genes, to construct effective diagnostic models, and to screen for potential therapeutic drugs.Methods:Key cell subgroups in CRS were identified through single-cell transcriptomic sequencing data. Essential genes associated with CRS were selected and diagnostic models were constructed by hdWGCNA (high dimensional weighted gene co-expression network analysis) and various machine learning algorithms. Causal inference analysis was performed using Mendelian randomization and colocalization analysis. Potential therapeutic drugs were identified using molecular docking technology, and the results of bioinformatics analysis were validated by immunofluorescence staining. Graphpad Prism, R, Python, and Adobe Illustrator software were used for data and image processing.Results:An increased proportion of basal and suprabasal cells was observed in CRS, especially in eosinophilic CRS with nasal polyps (ECRSwNP), with P=0.001. hdWGCNA revealed that the "yellow module" was closely related to basal and suprabasal cells in CRS. Univariate logistic regression and LASSO algorithm selected 13 key genes ( CTSC, LAMB3, CYP2S1, TRPV4, ARHGAP21, PTHLH, CDH26, MRPS6, TENM4, FAM110C, NCKAP5, SAMD3, and PTCHD4). Based on these 13 genes, an effective CRS diagnostic model was developed using various machine learning algorithms (AUC=0.958). Mendelian randomization analysis indicated a causal relationship between CTSC and CRS (inverse variance weighted: OR=1.06, P=0.006), and colocalization analysis confirmed shared genetic variants between CTSC and CRS (PPH4/PPH3>2). Molecular docking results showed that acetaminophen binded well with CTSC (binding energy:-5.638 kcal/mol). Immunofluorescence staining experiments indicated an increase in CTSC +cells in CRS. Conclusion:This study integrates various bioinformatics methods to identify key cell types and genes in CRS, constructs an effective diagnostic model, underscores the critical role of the CTSC gene in CRS pathogenesis, and provides new targets for the treatment of CRS.
3.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
4.HIV-1 Transmission among Injecting Drug Users is Principally Derived from Local Circulating Strains in Guangxi, China.
Ping CEN ; Hua Yue LIANG ; Yuan YANG ; Fei ZHANG ; Shi Xiong YANG ; Ju Cong MO ; Yi FENG ; Jie Gang HUANG ; Chuan Yi NING ; Chun Yuan HUANG ; Yao YANG ; Na LIANG ; Bing Yu LIANG ; Li YE ; Hao LIANG
Biomedical and Environmental Sciences 2023;36(5):418-430
OBJECTIVE:
The mode of human immunodeficiency virus (HIV) transmission via injection drug use (IDU) still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi.
METHODS:
We performed a molecular epidemiological investigation of infections across Guangxi from 2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.
RESULTS:
Among the 535 subjects, CRF08_BC (57.4%), CRF01_AE (28.4%), and CRF07_BC (10.7%) were the top 3 HIV strains; 72.6% of infections were linked to other provinces in the transmission network; 93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces, predominantly Guangdong and Yunnan; 92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs.
CONCLUSION
HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces. Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.
Humans
;
HIV-1/genetics*
;
HIV Infections
;
Drug Users
;
Phylogeny
;
Bayes Theorem
;
China/epidemiology*
;
Genotype
5.Differential diagnosis and surgical management in chondrosarcoma of the jugular foramen.
Da LIU ; Jian Ze WANG ; Jian Bin SUN ; Zhong LI ; Tong ZHANG ; Na SAI ; Yu Hua ZHU ; Wei Dong SHEN ; De Liang HUANG ; Pu DAI ; Shi Ming YANG ; Dong Yi HAN ; Wei Ju HAN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(6):544-551
Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.
Humans
;
Male
;
Female
;
Young Adult
;
Adult
;
Middle Aged
;
Facial Paralysis/etiology*
;
Diagnosis, Differential
;
Jugular Foramina
;
Retrospective Studies
;
Cough
;
Hoarseness
;
Neoplasm Recurrence, Local
;
Chondrosarcoma/surgery*
6.Clinical Practice of Multiple Disciplinary Team Care Model Following the Concept of Palliative Care for Advanced Head and Neck Cancer:Report of One Case.
Na LIU ; Rui SHA ; Xiao-Yan DAI ; Hong-Ju LIU ; Li-Jiang YU ; Tian-Ming XU
Acta Academiae Medicinae Sinicae 2023;45(1):77-79
We provided the palliative care of a multiple disciplinary team care mode to a patient diagnosed with advanced head and neck cancer and her caregivers.People-centered integrated health services were provided according to the specific needs and preferences of individuals.The team-based palliative care relieved the suffering and improved the quality of life of the patient and that of her family who were facing challenges associated with life-threatening illness.
Humans
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Female
;
Palliative Care
;
Quality of Life
;
Head and Neck Neoplasms/therapy*
7.Systematic review and Meta-analysis of efficacy and safety of Kushen Gelatum combined with antibiotics in treatment of bacterial vaginosis.
Ju-Wen ZHANG ; Li-Na ZHANG ; Ling XIONG ; Xu-Dong ZHANG ; Xue BAI ; Wei CHEN
China Journal of Chinese Materia Medica 2023;48(21):5946-5956
This study aims to systematically evaluate the clinical efficacy and safety of Kushen Gelatum combined with antibiotics for treating bacterial vaginosis. The randomized controlled trial(RCT) of Kushen Gelatum for treating bacterial vaginosis were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, and Cochrane Library with the time interval from inception to January 2023. Data were extracted from the included RCT by 2 investigators, including the sample size, characteristics of patients, interventions and controls, outcome indicators, and adverse effects. The Cochrane collaboration network's bias risk assessment tool was used for methodolo-gical quality evaluation of the included trials. RevMan 5.4 was employed to perform the Meta-analysis. A total of 19 RCTs were inclu-ded, involving 1 980 patients with bacterial vaginosis. Meta-analysis showed that, compared with nitroimidazoles alone, Kushen Gelatum + nitroimidazoles improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.24, 95%CI[1.13, 1.36], P<0.000 01), laboratory tests(RR=1.16, 95%CI[1.06, 1.26], P=0.000 9), and clinical symptoms(RR=1.26, 95%CI[1.08, 1.46], P=0.003), and reduced the leukocyte esterase positive rate(RR=0.29, 95%CI[0.17, 0.48], P<0.000 01) and the recurrence rate(RR=0.37, 95%CI[0.23, 0.58], P<0.000 1). Compared with lincomycin antibiotics(clindamycin) alone, Kushen Gelatum + lincomycin antibiotics(clindamycin) improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.06, 1.31], P=0.003) and laboratory tests(RR=1.27, 95%CI[1.04, 1.54], P=0.02), reduced the recurrence rate(RR=0.20, 95%CI[0.05, 0.75], P=0.02), and shortened the time to relief of burning sensation(MD=-1.70, 95%CI[-2.15,-1.26], P<0.000 01), vaginal itching(MD=-0.82, 95%CI[-1.30,-0.34], P=0.000 8), and abnormal leucorrhea(MD=-1.52, 95%CI[-1.98,-1.06], P<0.000 01). Compared with nitroimidazoles + probiotics, Kushen Gelatum + nitroimidazoles + probiotics improved the total response rate in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.02, 1.36], P=0.03) and reduced the recurrence rate(RR=0.27, 95%CI[0.09, 0.76], P=0.01). Kushen Gelatum combined with antibiotics demonstrates a potential therapeutic effect on bacterial vaginosis, whereas the number and quality of the relevant clinical studies remain to be improved. The process of clinical trial should be standardized to improve the quality of evidence, so as to provide strong evidence to guide the application of Kushen Gelatum in clinical practice.
Female
;
Humans
;
Anti-Bacterial Agents/adverse effects*
;
Clindamycin/adverse effects*
;
Vaginosis, Bacterial/chemically induced*
;
Nitroimidazoles/adverse effects*
8.Evaluation of the effectiveness of the evidence base multi-discipline critical strategies on the temperature and clinical outcomes in very preterm infants.
Hong ZHOU ; Yuan WANG ; Rong JU ; Xiao YANG ; Na Na WU ; Jun WANG ; Li Wen DING ; Jie FU ; Xue ZHONG
Chinese Journal of Preventive Medicine 2023;57(8):1266-1270
To evaluate the effectiveness of intervention plans developed by the evidence base multi-discipline critical strategies (EBPCS) on temperature and clinical outcomes in very preterm infants (VPIs) born at<32 weeks. Clinical data were collected from VPIs born in the delivery room/operating room of Chengdu Women's and Children's Central Hospital from May 1, 2021, to May 31, 2022, who required immediate temperature management and were transferred to the neonatal intensive care unit (NICU) of the hospital. The study population was randomly divided into a control group and an intervention group based on the random number table method, with 108 cases in each group. The control group implemented the conventional temperature management recommended by domestic guidelines, while the intervention group adopted EBPCS interventions compared to the control group. The differences in body temperature and clinical outcomes between the two groups were compared after the implementation of different temperature management strategies. A total of 216 VPIs were included. The intervention group had a lower incidence of hypothermia (30.55% vs. 87.03%, P<0.001), higher mean body temperature admitted to the NICU [(36.56±0.31) ℃ vs. (35.77±0.53) ℃, P<0.001], a lower dose of pulmonary surfactant [(115.94±36.96) mg/kg vs. (151.41±54.68) mg/kg, P=0.014], shorter duration of mechanical ventilation [(5.77±1.26) days vs. (14.19±4.63) days, P=0.006], and lower incidence of intraventricular haemorrhage (12.04% vs. 23.15%, P=0.032). The implementation of temperature intervention strategies developed by the EBPCS for VPIs after birth could prevent and reduce the incidence of hypothermia and improve clinical outcomes.
Child
;
Female
;
Humans
;
Infant
;
Infant, Newborn
;
Fever
;
Hypothermia/prevention & control*
;
Infant, Premature
;
Infant, Very Low Birth Weight
;
Temperature
9.Evaluation of the effectiveness of the evidence base multi-discipline critical strategies on the temperature and clinical outcomes in very preterm infants.
Hong ZHOU ; Yuan WANG ; Rong JU ; Xiao YANG ; Na Na WU ; Jun WANG ; Li Wen DING ; Jie FU ; Xue ZHONG
Chinese Journal of Preventive Medicine 2023;57(8):1266-1270
To evaluate the effectiveness of intervention plans developed by the evidence base multi-discipline critical strategies (EBPCS) on temperature and clinical outcomes in very preterm infants (VPIs) born at<32 weeks. Clinical data were collected from VPIs born in the delivery room/operating room of Chengdu Women's and Children's Central Hospital from May 1, 2021, to May 31, 2022, who required immediate temperature management and were transferred to the neonatal intensive care unit (NICU) of the hospital. The study population was randomly divided into a control group and an intervention group based on the random number table method, with 108 cases in each group. The control group implemented the conventional temperature management recommended by domestic guidelines, while the intervention group adopted EBPCS interventions compared to the control group. The differences in body temperature and clinical outcomes between the two groups were compared after the implementation of different temperature management strategies. A total of 216 VPIs were included. The intervention group had a lower incidence of hypothermia (30.55% vs. 87.03%, P<0.001), higher mean body temperature admitted to the NICU [(36.56±0.31) ℃ vs. (35.77±0.53) ℃, P<0.001], a lower dose of pulmonary surfactant [(115.94±36.96) mg/kg vs. (151.41±54.68) mg/kg, P=0.014], shorter duration of mechanical ventilation [(5.77±1.26) days vs. (14.19±4.63) days, P=0.006], and lower incidence of intraventricular haemorrhage (12.04% vs. 23.15%, P=0.032). The implementation of temperature intervention strategies developed by the EBPCS for VPIs after birth could prevent and reduce the incidence of hypothermia and improve clinical outcomes.
Child
;
Female
;
Humans
;
Infant
;
Infant, Newborn
;
Fever
;
Hypothermia/prevention & control*
;
Infant, Premature
;
Infant, Very Low Birth Weight
;
Temperature
10.Effect of miltirone on proliferation and apoptosis of leukemia THP-1 cells.
Shan-Shan CHEN ; Hua-Su ZHU ; Na DONG ; Ya-Ping ZHANG ; Min WU ; Ling-Hong LIU ; Qing SHI ; Dong LI ; Xiu-Li JU
China Journal of Chinese Materia Medica 2022;47(9):2541-2546
To investigate the toxicity and related mechanism of miltirone to human acute myeloid leukemia THP-1 cells. To be specific, the active components and targets of miltirone were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the target proteins were converted into standard gene names with UniProt. Acute leukemia-rela-ted target genes were screened from GeneCards and DisGeNET. Venn diagram was constructed with Venny 2.1 to yield the common targets of the disease and the drug. The protein-protein interaction(PPI) network was constructed by STRING and Cytoscape 3.8.2. THP-1 cells in the logarithmic growth phase were treated with dimethyl sulfoxide(DMSO), and 2.5, 5, 10, 15, and 20 μmol·L~(-1) miltirone for 24 h, respectively. The proliferation rate of cells was analyzed by carboxyfluorescein diacetate succinimidyl ester(CFSE), apoptosis rate by flow cytometry with Annexin V-PE/7 AAD staining, and cell morphology by acridine orange staining. Real-time quantitative PCR(qPCR) was employed to detect the mRNA levels of nuclear receptor coactivator 2(NCOA2), poly(ADP-ribose) polymerase-1(PARP1), B-cell lymphoma-2(Bcl-2)-associated X protein(Bax), Bcl-2, and cysteine aspartyl protease-3(caspase-3). The effect of miltirone on apoptosis was detected in presence of caspase inhibitor Z-VAD-FMK. A total of 26 targets of miltirone, 1 046 genes related to acute leukemia, and 6 common targets of the two were screened out. Flow cytometry result showed miltirone at 10 μmol·L~(-1) can inhibit proliferation and promote apoptosis of THP-1 cells. The typical manifestations of apoptosis, such as cell shrinkage, nuclear rupture, and chromatin agglomerate were displayed by acridine orange staining. The decreased mRNA levels of NCOA2 and PARP1 and increased Bax/Bcl-2 ratio and the activity of pro-apoptotic protein caspase-3 were observed. Z-VAD-FMK can attenuate the apoptosis-inducing effect of miltirone. This study indicates that miltirone can inhibit the proliferation and promote the apoptosis of THP-1 cells, by down-regulating NCOA2 and PARP1, raising Bax/Bcl-2 ratio, and activating caspase-3.
Apoptosis
;
Caspase 3/metabolism*
;
Cell Proliferation
;
Humans
;
Leukemia/metabolism*
;
Phenanthrenes/pharmacology*
;
Proto-Oncogene Proteins c-bcl-2/metabolism*
;
RNA, Messenger
;
THP-1 Cells
;
bcl-2-Associated X Protein/metabolism*

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