Objective:To describe the current status and efficacy of additional acarbose combined with insulin therapy in adult patients with type 1 diabetes mellitus (T1DM) .Methods:Adult T1DM patients with acarbose combined with insulin (acarbose group) or insulin alone (insulin group), age≥18 years and disease course≥1 year, who were registered in the T1DM Translational Medicine Research Project of Guangdong Province from June 2011 to December 2014 were enrolled in the study. The hemoglobin A1c (HbA 1c), body weight, body mass index (BMI), waist-to-hip ratio (WHR), insulin dosage and hypoglycemia of acarbose group and insulin group after 1 year were compared. Results:A total of 717 adult patients with T1DM were included (62 cases in acarbose group and 655 cases in insulin group). At the time of enrollment, the onset age of acarbose group was higher than that of insulin group [(31.1±12.3)years vs (27.4±12.4)years, P=0.019]; There were no significant differences in gender, age, course of disease, body weight, BMI, WHR, proportion of carbohydrate heat ≥50%, proportion of exercise time ≥150 min per week, HbA 1c, dosage of insulin, occurence of hypoglycemia and proportion of patients with dyslipidemia between the 2 groups (all P>0.05). After 1 year of follow-up, the HbA 1c in acarbose and insulin group decreased from baseline ( P=0.014, P<0.001), the body weight and BMI increased from baseline (all P<0.05), but WHR, insulin dosage and hypoglycemia occurrence were not statistically significant between the two groups (all P>0.05). After 1 year of follow-up, there were no significant difference in changes of HbA 1c, body weight, BMI, WHR, insulin dosage and hypoglycemia occurrence in acarbose group compared with insulin group from baseline (all P>0.05). Conclusions:In the clinical practice of T1DM treatment, acarbose is used more frequently in patients with a slightly older age of onset. Treatment of T1DM with insulin combined with acarbose did not increase the incidence of hypoglycemia, and no benefit was observed in improving HbA 1c, maintaining body weight, and reducing insulin use.

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.
Humans ; Carcinoma, Hepatocellular/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; Caspase 3/metabolism* ; Liver Neoplasms/genetics* ; Molecular Docking Simulation ; Sincalide/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Hep G2 Cells ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

This study investigated the effect and mechanism of morin in inducing autophagy and apoptosis in hepatocellular carcinoma cells through the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription protein 3(STAT3) pathway. Human hepatocellular carcinoma SK-HEP-1 cells were stimulated with different concentrations of morin(0, 50, 100, 125, 200, and 250 μmol·L~(-1)). The effect of morin on the viability of SK-HEP-1 cells was detected by Cell Counting Kit-8(CCK-8). The effect of morin on the proliferation and apoptosis of SK-HEP-1 cells was investigated using colony formation assay, flow cytometry, and BeyoClick~(TM) EdU-488 with different concentrations of morin(0, 125, and 250 μmol·L~(-1)). The changes in the autophagy level of cells treated with morin were examined by transmission electron microscopy and autophagy inhibitors. The impact of morin on the expression levels of proteins related to the Akt/mTOR/STAT3 pathway was verified by Western blot. Compared with the control group, the morin groups showed decreased viability of SK-HEP-1 cells in a time-and concentration-dependent manner, increased number of apoptotic cells, up-regulated expression level of apoptosis marker PARP, up-regulated phosphorylation level of apoptosis-regulating protein H2AX, decreased number of positive cells and the colony formation rate, an upward trend of expression levels of autophagy-related proteins LC3-Ⅱ, Atg5, and Atg7, and decreased phosphorylation levels of Akt, mTOR, and STAT3. These results suggest that morin can promote apoptosis, inhibit proliferation, and induce autophagy in hepatocellular carcinoma cells, and its mechanism of action may be related to the Akt/mTOR/STAT3 pathway.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis ; Autophagy ; Cell Proliferation ; Cell Line, Tumor ; STAT3 Transcription Factor/metabolism*

Objective: To understand the current situation regarding pediatric off-label use of drugs recommendations in Chinese clinical practice guidelines and to make recommendations for standardized reporting format regarding off-label use of drugs for children. Methods: This cross-sectional study was carried out by systematically searching the databases for Chinese guideline consensus articles published in journals between 2018 and 2020 and extracting recommendations regarding off-label use of drugs from those articles. The essential characteristics of the included guidelines, the ranking of off-label drug types, the order of drug information, the type of off-label drug use, and the percentage of citation studies on which the recommendations were based were analyzed. Results: Among 108 studies that included Chinese off-label guidelines and consensus, 364 recommendations on pediatric off-label use of drugs were included. The Chinese Medical Association published the most, 48 out of the 108 studies (44.4%), and of those 14 studies (13.0%) were on infectious and parasitic diseases. Of the 364 recommendations on off-label use of drugs, the most commonly addressed drugs were 16 recommendations (4.4%) for cyclosporine A, 11 recommendations (3.0%) for methotrexate , and 11 recommendations (3.0%) for fentanyl. The most commonly addressed drug categories were as follows: 68 recommendations (18.6%) were immune system drugs, 66 recommendations (18.1%) were anti-infectives, and 56 recommendations (15.4%) were oncology drugs. The most commonly addressed drug information accounts were as follows: 364 recommendations (100.0%) were indications, 204 recommendations (56.0%) were dosages, and 198 recommendations (54.4%) were the route of administration. Based on the instructions approved by the Chinese Food and Drug Administration, the main forms of the off-label drug were as follows: 175 recommendations (48.1%) were unapproved indications, 127 recommendations (34.9%) were unapproved populations, and 72 recommendations (19.8%) were unapproved ages. Only 129 recommendations (35.4%) were cited, mainly including clinical guidelines (48 studies, 23.4%), reviews (22 studies, 10.7%), and pediatric randomized controlled trials (22 studies, 10.7%). Conclusions: Off-label use of drugs is commonly recommended in pediatric guidelines and consensus documents written by Chinese authors. However, the reporting of the recommendations varies widely, and the quality of the supporting evidence is poor.
Child ; China ; Consensus ; Cross-Sectional Studies ; Humans ; Off-Label Use ; Pharmaceutical Preparations

ObjectiveTo determine the chemical constituents of burdock （Arctium lappa） leaves， and elucidate dynamic accumulation rule of four main components， in order to provide the basis for determining the suitable harvest time of burdock leaves. MethodSilica gel， macroporous resin， Sephadex LH-20， octadecylsilane chemically bonded silica （ODS）， microporous resin （MCI） column chromatography and reversed-phase preparative high performance liquid chromatography （HPLC） were used to isolate the main chemical constituents in burdock leaves. Their chemical structures were elucidated by spectroscopic techniques. HPLC-diode array detector （DAD） was used to analyze the dynamic accumulation of four components in burdock leaf. HPLC-DAD was performed on a Shim-pack GIST C₁₈ column （4.6 mm×250 mm， 5 μm） with mobile phase of acetonitrile （A）-0.3% phosphoric acid aqueous solution （B） （0-9 min， 13%A； 9-10 min， 13%-24%A； 10-30 min， 24%A）， flow rate of 1.0 mL·min^-1， column temperature of 40 ℃， and detection wavelength at 328 nm. ResultSeventeen compounds were isolated from burdock leaves， and identified as caffeic acid （1）， rutin （2）， kaempferol-3-O-rutinoside （3）， quercetin-3-O-β-D-glucopyranoside （4）， kaempferol-3-O-β-D-glucopyranoside （5）， chlorogenic acid （6）， isochlorogenic acid A （7）， daucosterol （8）， ursolic acid （9）， anemarrhenoside B （10）， （-）-secoisolariciresinol （11）， vladinol D （12）， melitensin （13）， esculetin （14）， 1-（-2-ethylphenyl）-1，2-ethanediol （15）， 1-（-4-ethylphenyl）-1，2-ethanediol （16）， 3-hydroxy-1-（4-hydroxy-3，5-dimethoxyphenyl）-1-propanone （17）. The contents of chlorogenic acid， rutin and kaempferol-3-O-rutinoside in burdock leaves showed an upward trend from April to August， and reached the highest in August. And the content of isochlorogenic acid A firstly increased and then decreased from April to August， and reached the highest in July. ConclusionCompounds 10， 12-17 were isolated from Arctium for the first time. Taking the contents of chlorogenic acid， rutin， kaempferol-3-O-rutinoside， and isochlorogenic acid A as indicators， considering the comprehensive development and utilization of burdock roots and leaves， it is recommended to harvest burdock leaves in mid-August.

Rich experience of clinical diagnosis and treatment has been accumulated in the developmental history of Chinese medicine, and the efficacy has been increasingly accepted by the public. However, the evaluation of clinical efficacy is currently based more on scientific evidence instead of merely the changes of patient symptoms. In Chinese medicine, the changes of major disease indicators, patient symptoms, and pathogenesis are the major criteria for the evaluation of clinical efficacy. The lack of well-accepted and uniform criteria and the uncertainty of subjective evaluation limit the development of clinical Chinese medicine. Evidence-based medicine combines clinical skills with the current best evidence. Narrative medicine, utilizing people's narratives in clinical practice, emphasizes patient feelings, willingness, and value orientation. The introduction of both evidence-based medicine and narrative medicine into the evaluation of clinical efficacy refers to the construction of the clinical efficacy evaluation system in a paradigm of participatory diagnosis and treatment. It can fully reflect the characteristics of Chinese medicine, respect the values of patients, and achieve universal clinical evidence. Therefore, it helps to improve the diagnosis and treatment, the relationship between doctors and patients, patients' life quality and decision-making awareness, and finally the new evaluation model of clinical efficacy of Chinese medicine.
Evidence-Based Medicine ; Humans ; Medicine, Chinese Traditional ; Narrative Medicine ; Physicians ; Treatment Outcome

Computational medicine is an emerging discipline that uses computer models and complex software to simulate the development and treatment of diseases. Advances in computer hardware and software technology, especially the development of algorithms and graphics processing units (GPUs), have led to the broader application of computers in the medical field. Computer vision based on mathematical biological modelling will revolutionize clinical research and diagnosis, and promote the innovative development of Chinese medicine, some biological models have begun to play a practical role in various types of research. This paper introduces the concepts and characteristics of computational medicine and then reviews the developmental history of the field, including Digital Human in Chinese medicine. Additionally, this study introduces research progress in computational medicine around the world, lists some specific clinical applications of computational medicine, discusses the key problems and limitations of the research and the development and application of computational medicine, and ultimately looks forward to the developmental prospects, especially in the field of computational Chinese medicine.
Algorithms ; Computer Simulation ; Humans

Objective: To produce the Chinese version of a new reflux symptom score (RSS) of laryngopharyngeal reflux disease (LPRD) and to evaluate its reliability, validity and clinical value. Methods: This was a retrospective study which contained 42 healthy volunteers and 135 possible LPRD patients. RSI,RFS,oropharyngeal pH monitoring (Dx-pH monitoring) and RSS of each patient were performed. RSS was performed again after 1 week. Confirmed LPRD patients were treated with proton pump inhibitor for 8 week. And RSS was performed again after treatment. Reliability and validity of RSS were evaluated. Results: The Cronbach's α coefficient of RSS was 0.77, which indicated good internal reliability of the new score. The results of test-retest found all P values were less than 0.05, which supported good external reliability. Comparing RSS with laryngopharyngeal reflux test results, the diagnostic coincidence rate was 84.44% (114/135), and the positive predictive value was 85.71% (114/133), which showed good criterion validity. After 8 weeks treatment of PPI, RSS decreased significantly (pretreatment 84.79±42.50,posttreatment 20.11±22.82,t=-10.54, P<0.001), indicating good reactivity of RSS. The score of quality of life impact (Qol) in possible LPRD patients was obviously higher than that of healthy volunteers (t=7.15,P<0.001). All patients and volunteers believed that RSS was a good way to evaluate their symptoms. Conclusions: The new score RSS have good internal and external reliability, criterion validity and reactivity. RSS can be one of the important reference indexes to evaluate LPRD.
Humans ; Laryngopharyngeal Reflux/diagnosis* ; Reproducibility of Results ; Retrospective Studies ; Quality of Life ; Proton Pump Inhibitors/therapeutic use* ; China

Objective: To evaluate the clinical effect of vonoprazan fumarate on laryngopharyngeal reflux disease (LPRD). Methods: The clinical data of 89 patients from June 2020 to January 2022, including 45 males and 44 females, aged 18-77 (45.54±13.53) years old, were retrospectively analyzed. All the patients were diagnosed as suspected LPRD according to reflux symptom index (RSI) and reflux finding score (RFS). Patients of the Vonoprazan Fumarate group were prescribed Vonoprazan Fumarate orally (20 mg, qd) for 8 weeks.Patients of the Esomeprazole group were prescribed Esomeprazole orally (20 mg, bid) for 8 weeks. RSI and RFS of all the patients before and after treatment were compared. SPSS 18.0 was used for statistics analysis. Results: Before treatment, gender, age, RSI and RFS of the two groups had no obvious differences. After treatment, RSI and RFS in both groups were alleviated significantly. In the vonorazan fumarate group, the RSI before treatment was 12.62±7.18, and after treatment was 4.74±3.87(t=6.91, P<0.001), the RFS was 10.78±2.29 before treatment and 8.24±2.45 after treatment (t=7.06, P<0.001). While in the esomeprazole group, the RSI was 13.27±6.95 before treatment and 6.02±4.28 after treatment (t=7.50, P<0.001), the RFS was 10.59±3.14 before treatment and 8.14±3.30 after treatment (t=5.41, P<0.001). There was no significant difference in the effective rate between the two groups (86.7% in the vonoprazan fumarate group and 77.3% in the esomeprazole group, χ²=1.443, P=0.486). Conclusion: Vonoprazan fumarate could effectively alleviate the symptoms and signs of LPRD patients. The effect of vonoprazan fumarate on LPRD is not inferior to Esomeprazole. It can be used as a supplement to PPI.
Humans ; Male ; Female ; Adult ; Middle Aged ; Laryngopharyngeal Reflux/diagnosis* ; Esomeprazole/therapeutic use* ; Retrospective Studies ; Fumarates/therapeutic use*