Hepatocellular carcinoma （HCC） is one of the most common malignant tumors with high incidence and mortality rates worldwide， which brings a huge burden to the physical and mental health and socio-economic life of patients. The adenosine monophosphate-activated protein kinase （AMPK） signaling pathway serves as the regulatory center of cellular energy metabolism and is closely associated with the biological activities of HCC cells， including autophagy， apoptosis， and angiogenesis， and it has become a hot topic in current cancer research. Traditional Chinese medicine drugs are abundant in natural components such as flavonoids， alkaloids， and phenols and have the characteristics of multiple targets， pathways， components， and hierarchies. By targeting the AMPK signaling pathway， these components can be used alone or in combination with conventional antitumor therapies to exert an anti-tumor effect on HCC from various aspects. This article reviews and summarizes the extracts of traditional Chinese medicine that target the AMPK signaling pathway for the prevention and treatment of HCC， in order to provide a theoretical basis and a reference for the clinical application of traditional Chinese medicine in the treatment of HCC and the development of related drugs.

Objectives:To investigate the rate and risk factors of tip displacement of umbilical venous catheterization (UVC) in preterm infants.Methods:This was a multicenter cohort study. Study population were preterm infants admitted to 44 tertiary hospitals in China between October 2019 and August 2021. Demographic information, general clinical data, UVC indwelling conditions and related complications were collected. The primary outcome was the rate of UVC tip displacement. The observation time points were 2 d and 7 d after UVC. They were grouped according to UVC displacement, gestational age, and birth weight. Binary Logistic regression was used to analyze the risk factors of UVC tip displacement.Results:The 2 086 preterm infants had a gestational age of (29.9±2.3) weeks and a birth weight of (1 248±298) g. There were 1 106 male preterm infants (53.0%). The rate of UVC displacement at 2 d and 7 d were 34.6% (721/2 086) and 33.6% (494/1 470), respectively, with no statistically significant difference ( χ2=0.35, P=0.533). Univariate analysis indicated that male infants, small gestational age, low birth weight and small catheter diameter were all risk factors for UVC tip displacement at the 2 d time point (all P<0.05). Multivariate analysis showed that small catheter diameter was an independent risk factor for tip displacement at both 2 d ( OR=0.47, 95% CI 0.34-0.66) and 7 d ( OR=0.39, 95% CI 0.25-0.59) time points (both P<0.001). Conclusions:The rate of UVC tip displacement is high in preterm infants. It should be avoided to deliberately select a small diameter catheter for UVC, and pay attention to the imaging monitoring of the tip position after UVC.

Objective:To evaluate the efficacy and safety of umbilical venous catheterization (UVC) by using different methods to estimate the insertion depth.Methods:PubMed, Embase and The Cochrane Library, CBM (SinoMed), CNKI, VIP Database, Wanfang Database and Chinese Medical Journal Full-text Database were electronically searched for literature on randomized controlled trials (RCTs) comparing different methods for estimating the insertion depth of UVC. The search period was from the establishment date of the above databases to April 15th, 2022. If 2 or more studies were available for each pairwise comparison, a meta-analysis was conducted using the RevMan 5.3 software. However, if only 1 study was included for each pairwise comparison, SPSS 26.0 statistical software is used for statistical analysis using the chi-square test.Results:A total of 9 RCTs were included in the final meta-analysis, with a total of 1 281 infants, using 6 methods for estimating the depth of UVC. Compared with the Shukla formula, the Dunn method showed a statistically significant improvement in the correct place rate at the first UVC attempt ( RR=1.27, 95% CI 1.09-1.47, P=0.002). When comparing the Dunn method with the revised Shukla formula, the difference in the correct place rate at the first UVC attempt was statistically significant (21.4% vs. 33.5%, χ2=7.24, P=0.007). There was no statistically significant difference in the correct place rate at the first UVC attempt between the Dunn method and the formula based on BW, the JSS formula and the revised Shukla formula, and the method based on anatomical marks and the Shukla formula. There was no statistically significant difference in the incidence of UVC complications between the Dunn method and the Shukla formula, and between the method based on anatomical marks and the Shukla formula. Conclusions:Comparing to Shukla formula, Dunn method has a higher correct place rate at the first attempt. The incidence of complications is similar between the different pairwise comparison methods.

Objective:To investigate frailty in older patients with comorbidities and explore related risk factors.Methods:A cross-sectional study was conducted with an enrollment of 746 patients aged 65 years or older with comorbidities in the Wanshoulu Road area of Beijing from April 2019 to December 2020.A total of 617 patients with comorbidities were finally included, aged(85.6±4.8)years, including 358 women(58.0%); According to the FRAIL scale, 617 patients with comorbidities were divided into a frail group(156 cases, 25.3%)and a non-frail group(461 cases, 74.7%). Demographic data and information on comorbidities were collected.Univariate and multivariate Logistic regression analyses of risk factors were conducted.Results:Among 617 patients with comorbidities, the common chronic diseases in descending order were hypertension(497 cases, 80.6%), coronary heart disease(375 cases, 60.8%), osteoporosis(357 cases, 57.9%), osteoarthritis(281 cases, 45.5%), type 2 diabetes(211 cases, 34.2%), stroke and/or transient ischemic attack(193 cases, 31.3%), chronic lung disease(144 cases, 23.3%), tumor(133 cases, 21.6%), chronic kidney disease(92 cases, 14.9%), and heart failure(58 cases, 9.4%). Univariate logistic regression analysis showed that age, type 2 diabetes, coronary heart disease, heart failure, chronic lung disease, stroke/transient ischemic attack, cancer and osteoarthritis were influencing factors for frailty( P<0.05). Multivariate logistic regression analysis showed that age, type 2 diabetes, heart failure, chronic lung disease, cancer and osteoarthritis were risk factors for frailty( OR=1.076, 1.806, 3.275, 3.371, 1.640, 2.227, all P<0.05). Conclusions:Old age, type 2 diabetes, heart failure, chronic lung disease, tumor and osteoarthritis are closely related to frailty in elderly patients with comorbidities.Proactive and effective prevention and intervention should be instituted to target risk factors for frailty to reduce the occurrence of adverse outcomes.

Objective:To systematically evaluate the safety of family integrated care (FICare) model in neonatal intensive care unit (NICU).Methods:Multiple medical databases were searched for clinical studies on FICare in NICU published from January 1, 2010 to May 28, 2022. The quality of the literature was evaluated using Risk?of?Bias?2 tool?and cohort evaluation criteria from the Cochrane Systematic Evaluation Manual depending on the types of studies included. Meta-analysis was performed using Review Manager 5.3 software.Results:Six randomized controlled trials and four cohort studies were included for meta-analysis. The results of meta-analysis showed that compared with the traditional care model, FICare model did not increase the risk of nosocomial infection ( RR=0.75, 95% CI 0.46-1.24, P=0.27) and unstable medical conditions ( RR=0.86, 95% CI 0.61-1.22, P=0.40). No significant difference existed in the all-cause mortality between FICare and traditional care ( RR=2.74, 95% CI 0.88-8.57, P=0.08). Conclusions:FICare does not increase the risk of nosocomial infection, unstable medical conditions and adverse events compared with traditional care. It is safe and feasible to implement FICare in NICU.

ObjectiveTo study the effect of organophosphate-solubilizing bacteria and compound bacteria on the photosynthesis and physiological and biochemical characteristics of leaves of Paris polyphylla var. yunnanensis， and to provide a reference for selecting suitable bacterial fertilizers in artificial cultivation of this medicinal species. MethodPot experiment was carried out indoor and the following groups were designed： control （CK）， inoculation with Bacillus mycoides （S1）， inoculation with B. wiedmannii （S2）， inoculation with B. proteolyticus （S3）， inoculation with B. mycoides and B. wiedmannii （S4）， inoculation with B. mycoides and B. proteolyticus （S5）， inoculation with B. wiedmannii and B. proteolyticus （S6）， and inoculation with B. mycoides， B. wiedmannii and B. proteolyticus （S7）. Then， the growth and development， photosynthesis， and various physiological and biochemical indexes of the leaves of this species were observed. ResultCompared with CK， the treatment groups showed decrease in content of malondialdehyde in the leaves （P<0.05）， particularly S7 （content was only about 1/3 that of the CK）. The leaf area， photosynthetic parameters， photosynthetic pigment content， soluble sugar content， soluble protein content， and activity of superoxide dismutase （SOD）， peroxidase （POD）， and catalase （CAT） in leaves of the treatment groups were all improved. Among them， the leaf area， soluble sugar content， and soluble protein content were the highest in S7， which were 2.8， 2.1， and 2.2 times that of the CK， respectively. SOD activity peaked in S6 （2.9 times higher than that in the CK） and the highest activity of POD and CAT was detected in S5 （1.5 times and 2.1 times， respectively higher than that in the CK）. ConclusionInoculation with different organophosphate-solubilizing bacteria or compound bacteria can promote the growth and development of P. polyphylla var. yunnanensis and improve its resistance to stresses. The combination of B. mycoides and B. proteolyticus and the combination of the three achieved the have the best effect. This study provides a reference for the selection of bacterial fertilizers for artificial cultivation of P. polyphylla var. yunnanensis.

OBJECTIVE：To systematically evaluate the efficacy and safety of sodium-glucose co-transporter 2 （SGLT-2）inhibitors combined with insulin in the treatment of type 1 diabetes mellitus（T1DM），and to provide evidence-based reference for clinical treatment of T1DM. METHODS：Retrieved from PubMed，Cochrane library，Embase，Clinical Trials，CNKI，CBM and Wanfang database，randomized controlled trials（RCT）about SGLT-2 inhibitor（trial group）versus placebo（control group）in the treatment of T1DM based on insulin treatment were collected during the inception to Feb. 2020. After data extraction of literatures met inclusion criteria，Cochrane risk bias evaluation tool 5.1.0 was used to evaluate its quality，and Meta-analysis was perfomed by using Stata 12.0 software. RESULTS：A total of 11 RCTs were included，involving 7 003 patients. The results of Meta-analysis showed that the decrease of HbA1c [SMD＝－0.49，95％CI（－0.53，－0.44），P＜0.001]，the proportion of patients with HbA1c≥ 0.5％ and without severe hypoglycemia [OR＝3.93，95％ CI（3.49，6.21），P＜0.001]，the proportion of patients with HbA1c≥ 0.5％ [OR＝2.65，95％CI（2.25，3.12），P＜0.001]，the target rate of HbA1c level＜7.0％ [OR＝2.85，95％CI（2.44，3.33），P＜0.001] and the decrease of body weight [SMD＝－0.83，95％CI（－0.96，－0.70），P＜0.001] in trial group were significantly larger or higher than control group；the decrease values of daily insulin dosage，fasting blood glucose，postprandial blood glucose，systolic blood pressure and diastolic blood pressure in trial group were significantly higher than those in the control group，with statistical significance（P≤0.011）. The total incidence of ADR [OR＝1.14，95％CI（1.04，1.26），P＝0.007]，the incidence of SGLT-2 inhibitor related ADR [OR＝2.17，95％CI（1.75，2.99），P＜0.001]，the incidence of severe ADR [OR＝1.48，95％CI（1.24，1.77），P＜0.001]， the incidence of genital infection [OR＝3.84，95％CI（3.14，4.69），P＜0.001]，the incidence of diarrhea [OR＝1.47，95％CI（1.09，1.97），P＝0.011]，the incidence of fluid reduction related ADR [OR＝2.05，95％CI（1.37，3.08），P＝0.001]，the incidence of ketosis related ADR [OR＝4.18，95％CI（3.15，5.55），P＜0.001]，the incidence of ketoacidosis [OR＝4.33，95％CI（3.01，6.23），P＜0.001] and the incidence of severe ketoacidosis [OR＝5.06，95％CI（2.61，9.81），P＜0.001] were significantly higher than control group， with statistical significance. There was no statistical significance in the incidence of hypoglycemia，severe hypoglycemia，urinary tract infection or kidney injury between 2 groups. CONCLUSIONS：SGLT-2 inhibitors for the treatment of T1DM can significantly improve the blood glucose，reduce body weight and daily insulin dose，lower systolic blood pressure and diastolic blood pressure，while dose not increase the risk of hypoglycemia，urinary tract infections and renal impairment but increase the risk of total ADR as well as the risk of ADR such as genital infection，diarrhea，ketoacidosis，to which should be paid attention.

Objective To assess the effectiveness of Chinese materia medica (CMM) as adjuvant therapy of antibacterial for pediatric mesenteric lymphadenitis.Methods Retrieved RCT research of CMM as adjuvant therapy of antibacterial for pediatric mesenteric lymphadenitis from CNKI,Wanfang,VIP,PubMed,and Medline database from 1980 to 2016.Literatures were selected according to the inclusion and exclusion crteria,Jadad scores method was used to evaluate the literatures and meta-analysis was performed by RevMan 5.3.Results A total of 34 randomized controlled trials were included.Meta-analysis showed that the trial group was superior to the control group in terms of efficiency,cure rate,remission time of main symptoms,mesenteric lymph node recovery,and recurrence rate,there was statistical difference.Conclusions CMM as adjuvant therapy of antibacterial for pediatric mesenteric lymphadenitis is more effective than the use of antibacterial alone.

At present,the study of intestinal absorption of oral drugs mainly includes in vitro,in vivo and in situ methods.In view of the advantages of in situ intestinal perfusion such as simple operation,mature technology,controllable,ensure the neuroendocrine regulation and blood supply,and so on,which could better reflect the true situation of drug absorption.In this study,the research methods and characteristics of intestinal absorption of oral drugs were systematically introduced.The recirculating perfusion method and single-pass perfusion method were compared,and several volume correction methods were also introduced.In order to ensure the operability and accuracy of experimental results,proper experiment method of intestinal absorption will be adopt according to the factors such as drug characters,experiment requirements,experimental conditions,and so on.The article provides a scientific basis for the development of pharmaceutical dosage and clinical rational drug use.

OBJECTIVE:To provide reference for clinical individual medication of voriconatole. METHODS:The distribution of MIC of voriconazole to Aspergillus fumigatus and Candida albicans were summarized as well as the pharmacokinetic parameters of voriconazole in different populations. Using probability of target attainment(PTA)and cumulative fraction of response(CFR)as indexes,crystal ball software 11.1.2.4 was used for Monte Carlo simulation of different dosage regimens of same population and same dosage regimen of different populations. RESULTS:For children with impaired immunity,when the drug doses of were 4,6 mg/kg and MIC was lower than 0.125 mg/L,PTA was higher than 90%;when the drug doses was increased to 8 mg/kg and MIC was lower than 0.125 mg/L,PTA was higher than 90%. For different populations receiving same dosage regimens(4 mg/kg),MIC of teenagers with impaired immunity was lower than 0.25 mg/L and those of healthy adults,patients underwent hematopoietic stem cell transplantation and adults with impaired immunity were all lower than 0.5 mg/L,PTA was higher than 90%. CFR to A. fumigatus were 42.53%,58.41%,77.74%,70.16%,89.40%,93.72%,95.42% and CFR to C. albicans were 96.68%,97.13%,97.94%, 97.54%,98.07%,98.28%,98.35%among children with impaired immunity receiving different drug doses(4,6,8 mg/kg)and dif-ferent populations receiving drug dose of 4 mg/kg(teenagers with impaired immunity,healthy adults,patients underwent hemato-poietic stem cell transplantation,adults with impaired immunity). CONCLUSIONS:Various dosage regimens of different popula-tions included in this study could effectively control C. albicans infection. It is necessary to increase the drug dose of children and teenagers with impaired immunity in order to meet the needs of A. fumigatus infection treatment.