Multi-center Randomized Controlled Clinical Trial of Huangqi Injection Combined with Buzhong Yiqi Acupuncture in Treatment of Chronic Fatigue Syndrome with Qi Deficiency / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Huangqi injection combined with Buzhong Yiqi acupuncture in the treatment of chronic fatigue syndrome （CFS） with Qi deficiency and its effects on TCM syndromes， fatigue symptoms， serum superoxide dismutase （SOD）， malondialdehyde （MDA）， and oxidized low-density lipoprotein （ox-LDL） levels. MethodA total of 200 patients with CFS of Qi deficiency were randomly divided into a control group （100 cases） and an observation group （100 cases）. The control group was treated with vitamin B compounds， and the observation group was treated with Huangqi injection combined with Buzhong Yiqi acupuncture for two weeks. The scores of TCM syndromes， fatigue symptoms， levels of serum SOD， MDA， and ox-LDL and the incidence of adverse reactions were observed and compared before and after treatment in two groups. ResultAfter treatment， the total effective rate of the control group was 54.34% （50/92）， while that of the observation group was 88.54% （85/96）. The total effective rate of the observation group was higher than that of the control group （χ2=27.13，P<0.05）. Compared with those in the two groups before treatment， scores of fatigue self-assessment scale （FSAS）， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the two groups after treatment were significantly decreased （P<0.05）. After treatment， scores of FSAS， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， TCM syndrome scores in the two groups after treatment were significantly decreased （P<0.05）. After treatment， TCM syndrome scores in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， MDA levels in the two groups were significantly decreased （P<0.05）， ox-LDL levels in the observation group were significantly decreased （P<0.05）， and SOD levels were significantly increased （P<0.05）. After treatment， compared with those in the control group， the serum MDA and ox-LDL levels in the observation group were significantly decreased （P<0.05）， and the serum SOD was significantly increased （P<0.05）. No serious adverse events or adverse reactions occurred during this clinical trial. ConclusionHuangqi injection combined with Buzhong Yiqi acupuncture has a good clinical curative effect in the treatment of CFS with Qi deficiency， which can effectively improve the fatigue symptoms of patients， increase the level of SOD， and reduce the level of serum MDA and ox-LDL. It is related to the production of antioxidants， inhibiting the production of lipid peroxides， and improving the body's ability to resist oxidative stress.

Inhibitory Effect of Paeonol on Vascular Smooth Muscle Cell Senescence by Reducing SIRT6/PARP1-mediated DNA Damage / 中国实验方剂学杂志

ObjectiveTo investigate whether the effects of paeonol （Pae） on angiotensin Ⅱ （AngⅡ）-induced senescence in vascular smooth muscle cells （VSMCs） were related to angiotensinogen of silencing regulatory information factor 6 （SIRT6）/adenosine diphosphate ribose polymerase 1 （PARP1） signaling pathway in VSMCs. MethodThe model of VSMC-stress aging induced by AngⅡ （100 nmol·L-1） was established. The rats were divided into normal group， model group， low， medium， and high-concentration Pae groups （30， 60， 120 μmol·L-1）. The positive rate of cell senescence was detected by SA-β-Gal staining， the ability of cell proliferation was detected by the cell counting kit-8 （CCK-8） method， the expression of SIRT6， PARP1， p16， p21， p53， proliferating cell nuclear antigen （PCNA）， deoxyribonucleic acid （DNA）-damaged protein γ-H2AX was detected by Western blot， and VSMC proliferation was detected by EdU staining. The silenced VSMCs were prepared by siRNA-SIRT6 transfection， and the protein expressions of SIRT6， PARP1， p16， and γ-H2AX in VSMCs silenced by SIRT6 were observed. ResultThe results of SA-β-Gal staining showed that the senescence positive rate of SA-β-Gal staining in the model group was higher than that in the normal group （P<0.01）， and the positive rate of SA-β-Gal staining in the Pae group was significantly lower than that in the model group （P<0.05， P<0.01）. The results of Western blot showed that as compared with the normal group， the expression of PCNA， SIRT6， and PARP1 in the model group was down-regulated， and the expression of aging-related proteins p16， p21， p53， and γ-H2AX was up-regulated in the model group （P<0.05， P<0.01）. Compared with the model group， Pae promoted the protein expression of PCNA， SIRT6， and PARP1 and inhibited the protein expression of p16， p21， p53， and γ-H2AX in a dose-dependent manner （P<0.05， P<0.01）. The results of EdU staining showed that the number of EdU positive cells in the model group was lower than that in the normal group （P<0.01）， and the number of EdU positive cells in Pae groups was significantly higher than that in the model group （P<0.05， P<0.01）. After SIRT6 silencing， the effects of Pae on promoting SIRT6 and PARP1 and inhibiting P16 were reversed （P<0.05， P<0.01）. In addition， the addition of SIRT6 inhibitor （IN-1） promoted the occurrence of cell senescence induced by AngⅡ （P<0.05， P<0.01）. ConclusionPae can effectively inhibit the aging of VSMCs， and its mechanism may be related to the regulation of SIRT6/PARP1 signal pathway.

Establishment method and significance of birthweight curve and reference in single center / 中华妇产科杂志

Objective: To establish neonatal birthweight percentile curves based on single-center cohort database using different methods, compare them with the current national birthweight curves and discuss the appropriateness and significance of single-center birthweight standard. Methods: Based on a prospective first-trimester screening cohort at Nanjing Drum Tower Hospital from January 2017 to February 2022, the generalized additive models for location, scale and shape (GAMLSS) and semi-customized method were applied to generate local birthweight percentile curves (hereinafter referred to as the local GAMLSS curves, semi-customized curves) for 3 894 cases who were at low risk of small for gestation age (SGA) and large for gestation age (LGA). Infants were categorized as SGA (birth weight<10th centile) by both semi-customized and local GAMLSS curves, semi-customized curves only, or not SGA (met neither criteria). The incidence of adverse perinatal outcome between different groups was compared. The same method was used to compare the semi-customized curves with the Chinese national birthweight curves (established by GAMLSS method as well, hereinafter referred to as the national GAMLSS curves). Results: (1) Among the 7 044 live births, 404 (5.74%, 404/7 044), 774 (10.99%, 774/7 044) and 868 (12.32%, 868/7 044) cases were diagnosed as SGA according to the national GAMLSS curves, the local GAMLSS curves and the semi-customized curves respectively. The birth weight of the 10th percentile of the semi-customized curves was higher than that of the local GAMLSS curves and the national GAMLSS curves at all gestational age. (2) When comparing semi-customized curves and the local GAMLSS curves, the incidence of admission to neonatal intensive care unit (NICU) for more than 24 hours of infants identified as SGA by semi-customized curves only (94 cases) and both semi-customized and local GAMLSS curves (774 cases) was 10.64% (10/94) and 5.68% (44/774) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks of infants identified as SGA by the semi-customized curves only and both semi-customized and local GAMLSS curves was 12.77% (12/94) and 9.43% (73/774), 9.57% (9/94) and 2.71% (21/774), 24.47% (23/94) and 7.24% (56/774) respectively, which were significantly higher than those of the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. (3) When comparing semi-customized curves and the national GAMLSS curves, the incidence of admission to NICU for more than 24 hours of infants identified as SGA by semi-customized curves only (464 cases) and both semi-customized and national GAMLSS curves (404 cases) was 5.60% (26/464) and 6.93% (28/404) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); all P<0.001]. The incidence of emergency cesarean section or forceps delivery for non-reassuring fetal status (NRFS) in infants identified as SGA by semi-customized curves only and both semi-customized and national GAMLSS curves was 4.96% (23/464) and 12.38% (50/404), both significantly higher than that in the non SGA group [2.57% (159/6 176); all P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks in the semi-customized curves only group and both semi-customized and national GAMLSS curves group was 8.84% (41/464) and 10.89% (44/404), 4.31% (20/464) and 2.48% (10/404), 10.56% (49/464) and 7.43% (30/404) respectively, all significantly higher than those in the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. Conclusion: Compared with the national GAMLSS birthweight curves and the local GAMLSS curves, the birth weight curves established by semi-customized method based on our single center database is in line with our center' SGA screening, which is helpful to identify and strengthen the management of high-risk infants.

Research on applying genetic and environmental risk score in risk-adapted colorectal cancer screening / 中华流行病学杂志

Objective: To evaluate the effectiveness of a risk-adapted colorectal cancer screening strategy constructed utilizing genetic and environmental risk score (ERS). Methods: A polygenic risk score (PRS) was constructed based on 20 previously published single nucleotide polymorphisms for colorectal cancer in East Asian populations, using 2 160 samples with MassARRAY test results from a multicenter randomized controlled trial of colorectal cancer screening in China. The ERS was calculated using the Asia-Pacific Colorectal Screening Score system. Logistic regression was used to analyze the association between PRS alone and PRS combined with ERS and colorectal neoplasms risk, respectively. We also designed a risk-adapted screening strategy based on PRS and ERS (high-risk participants undergo a single colonoscopy, low-risk participants undergo an annual fecal immunochemical test, and those with positive results undergo further diagnostic colonoscopy) and compared its effectiveness with the all-acceptance colonoscopy strategy. Results: The high PRS group had a 26% increased risk of colorectal neoplasms compared with the low PRS group (OR=1.26, 95%CI: 1.03-1.54, P=0.026). Participants with the highest PRS and ERS were 3.03 times more likely to develop advanced colorectal neoplasms than those with the lowest score (95%CI: 1.87-4.90, P<0.001). As the risk-adapted screening simulation reached the third round, the detection rate of the PRS combined with ERS strategy was not statistically different from the all-acceptance colonoscopy strategy (8.79% vs. 10.46%, P=0.075) and had a higher positive predictive value (14.11% vs. 10.46%, P<0.001) and lower number of colonoscopies per advanced neoplasms detected (7.1 vs. 9.6, P<0.001). Conclusion: The risk-adapted screening strategy combining PRS and ERS helps achieve population risk stratification and better effectiveness than the traditional colonoscopy-based screening strategy.

A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies / 中华血液学杂志

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.

Clinical efficacy of intracoronally targeted recombinant human urokinase combined with percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) with high thrombus burden / 中国临床药理学与治疗学

AIM: To study the effect of of intracoronally targeted recombinant human urokinase combined with percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) with high thrombus burden. METHODS: In this retrospective analysis study, 85 AMI patients with heavy thrombus burden admitted to Wuhu Second people's Hospital for percutaneous coronary intervention (PCI) from November 2020 to November 2022 were divided into observation group (n=37) and control group (n=48) according to different treatment methods.Recombinant human urokinase were used for coronary intervention in observation group. The control group was not treated with recombinant human urokinase. The myocardial injury markers troponinI (cTnI) and creatine kinase (CK) within 24 h after PCI, the percentage of segment resolution≥50% 1 h after PCI, intraoperative coronary lesions blood flow, the incidence of adverse cardiovascular events (MACE) during hospitalization, and cardiac function indexleft ventricular end diastolic (LVED), fractional shortening (FS), left ventricular ejection fraction (LVEF) level change one month discharge were compared between the two groups after PCI. RESULTS: After PCI, the levels value of cTnI and creatine kinase in the observation group at within 24 h after PCI were (69.35±16.31) ng/mL vs. (80.52±15.20) ng/mL, (3 136.27±1 952.52) U/L vs. (4 554.51±1 982.34) U/L, which were significantly lower than those in the control group (P0.05) CONCLUSION: Intracoronally targeted application of recombinant human urokinase combined with percutaneous coronary intervention (PCI) has a significant effect on AMI with heavy thrombus burden, which can effectively improve cardiac function, coronary blood flow and myocardial reperfusion, and reduce myocardial damage without increasing the risk of MACE

Treatment advice of small molecule antiviral drugs for elderly COVID-19 / 中国药理学通报

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Paeonol reduces microbial metabolite α-hydroxyisobutyric acid to alleviate the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in atherosclerosis mice / 中国天然药物

Gut microbiota dysbiosis is an avenue for the promotion of atherosclerosis (AS) and this effect is mediated partly via the circulating microbial metabolites. More microbial metabolites related to AS vascular inflammation, and the mechanisms involved need to be clarified urgently. Paeonol (Pae) is an active compound isolated from Paeonia suffruticoas Andr. with anti-AS inflammation effect. However, considering the low oral bioavailability of Pae, it is worth exploring the mechanism by which Pae reduces the harmful metabolites of the gut microbiota to alleviate AS. In this study, ApoE-/- mice were fed a high-fat diet (HFD) to establish an AS model. AS mice were administrated with Pae (200 or 400 mg·kg-1) by oral gavage and fecal microbiota transplantation (FMT) was conducted. 16S rDNA sequencing was performed to investigate the composition of the gut microbiota, while metabolomics analysis was used to identify the metabolites in serum and cecal contents. The results indicated that Pae significantly improved AS by regulating gut microbiota composition and microbiota metabolic profile in AS mice. We also identified α-hydroxyisobutyric acid (HIBA) as a harmful microbial metabolite reduced by Pae. HIBA supplementation in drinking water promoted AS inflammation in AS mice. Furthermore, vascular endothelial cells (VECs) were cultured and stimulated by HIBA. We verified that HIBA stimulation increased intracellular ROS levels, thereby inducing VEC inflammation via the TXNIP/NLRP3 pathway. In sum, Pae reduces the production of the microbial metabolite HIBA, thus alleviating the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in AS. Our study innovatively confirms the mechanism by which Pae reduces the harmful metabolites of gut microbiota to alleviate AS and proposes HIBA as a potential biomarker for AS clinical judgment.

Pressure-induced differentiation of rabbit retinal stem cells into retinal ganglion cells / 中华实验眼科杂志

Objective:To investigate the effect of pressure on the differentiation of rabbit retinal stem cells (RSCs) co-cultured with retinal ganglion cells (RGCs).Methods:SPF grade New Zealand rabbits on the day 22 of gestation were selected, and embryos were removed to obtain retinal ciliary margin pigment epithelial tissue and culture primary RSCs.Six SPF grade newborn New Zealand rabbits were selected, and retinal neuroepithelial layer tissues were isolated to culture primary RGCs.Rabbit RSCs cultured in vitro were identified by immunofluorescence staining of nestin antibody, bromodeoxyuridine (BrdU) cell proliferation assay kit, RSCs spontaneously differentiated cells immunofluorescence detection and flow cytometry.RGCs were identified through immunofluorescence staining of Brn3b antibody and Thy1.1 antibody.A co-culture system of RGCs and RSCs cultured in the upper and lower layers of a transwelll plate respectively was constructed.The mRNA and protein expression levels of nestin and Thy1.1 in RSCs and differentiated cells under pressures of 0, 20, 40, 60, 80 mmHg (1 mmHg=0.133 kPa) were detected by real-time fluorescence quantitative PCR and Western blot.The feeding and use of laboratory animals were in accordance with the Regulations on the Administration of Laboratory Animals promulgated by the State Science and Technology Commission.The study protocol was approved by the Ethics Committee of Yunnan University Affiliated Hospital (No.KPRC-IACUC17008). Results:RSCs cultured in vitro were nestin-positive.The percentage of BrdU-positive isolated RSCs was (92.26±3.28)%.Some cells differentiated from RSCs were Brn3b-positive, accounting for (13.00±3.06)%, and some were GS-positive, accounting for (31.60±3.67)%.RGCs cultured in vitro were Brn3b- and Thy1.1-positive.There were statistically significant differences in the relative mRNA and protein expressions of nestin and Thy1.1 between RSCs and differentiated cells under different pressures (mRNA: F=127.600, 137.400; both at P<0.01; protein: F=82.480, 158.700; both at P<0.001). The relative mRNA and protein expressions of nestin were significantly reduced in RSCs, and relative mRNA and protein expressions of Thy1.1 were significantly increased in differentiated cells at 20, 40, 60 and 80 mmHg in comparison with 0 mmHg (all at P<0.05). When the pressure was 40 mmHg, the relative mRNA and protein expressions of nestin were lowest in RSCs, and the relative mRNA and protein expressions of Thy1.1 in differentiated cells were highest. Conclusions:Within a certain range, pressure can promote the differentiation of RSCs co-cultured with RGCs into ganglion-like cells, and excessive pressure can inhibit the differentiation of RSCs.

Evaluation of sequential organ failure assessment score, Braden Scale score, and nutritional indicators in patients with pressure ulcer after spinal cord injury / 中国基层医药

Objective:To investigate the effects of sequential organ failure assessment (SOFA) score, Braden Scale score, and nutritional indicators in patients with pressure ulcer after spinal cord injury.Methods:Eighty spinal cord injury patients with pressure ulcer who received treatment in the First People's Hospital of Huzhou, China between January 2019 and February 2020 were included in the patient group. Among these patients, 22 had stage I pressure ulcer, 33 had stage II pressure ulcer, and 25 had stage III pressure ulcer. An additional 140 patients with spinal cord injury but without pressure ulcer who concurrently received treatment in the same hospital were included in the control group. SOFA score, Braden Scale score and nutritional indicators were compared between the two groups. The correlation between SOFA score, Braden scale score and nutritional indicators was analyzed.Results:There were no significant differences in gender, age, hypertension, diabetes, operation condition and American Spinal Injury Association Impairment Scale score between the two groups (all P > 0.05). There were significant differences in body mass index [(24.25 + 1.44) kg/m 2vs. (27.68 + 2.21) kg/m 2, t = 12.44, P < 0.05], use of vasoactive drugs (29.29% vs. 43.75%, χ 2 = 4.71, P < 0.05), length of hospital stay [(10.71 + 2.62) days vs. (16.39 + 3.05) days, t = 14.56, P < 0.05]. SOFA score in the observation group was significantly higher than that in the control group [(9.72 ± 1.18) points vs. (4.51 ± 0.30) points, t = 49.58, P < 0.001]. Braden scale score in the observation group was significantly lower than that in the control group [(10.64 ± 1.05) points vs. (13.49 ± 2.28) points, t = 10.55, P < 0.001]. Serum level of hemoglobin, prealbumin, and albumin in the observation group was (81.03 ± 8.48) g/L, (145.29 ± 14.72) mg/L, (20.24 ± 2.05) g/L, respectively, which were significantly lower than those in the control group [(107.25 ± 10.14) g/L, (170.86 ± 23.75) mg/L, (32.38 ± 4.07) g/L, t = 19.54, 8.71, 24.91, all P < 0.001]. Spearman correlation analysis showed that SOFA score was positively correlated with serum level of hemoglobin, prealbumin, and albumin ( r = 0.50, 0.64, 0.71, all P < 0.05). SOFA score was negatively correlated with Braden Scale score ( r = -0.51, -0.62, -0.75, all P < 0.05). Conclusion:Pressure ulcer in spinal cord injury is caused by combined action of multiple factors. SOFA score, Braden scale score, and combined detection of hemoglobin, prealbumin, and albumin can be used to better evaluate pressure ulcer after spinal cord injury.

Study on effect of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" on atherosclerosis in ApoE~(-/-) mice based on liver metabonomics / 中国中药杂志

In this study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS)-based liver metabolomics approach was used to explore the mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in improving atherosclerosis(AS) of mice with apolipoprotein E gene knockout(ApoE~(-/-)). AS mouse model was induced by high-fat diet. The pathological and biochemical indexes such as the histopathological changes, body weight, liver weight, blood lipid level and inflammatory factors in the liver of mice were determined. The metabolic profiling of mice liver samples was performed with UPLC-Q-TOF-MS. Multiple statistical analysis methods including partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed to screen and identify biomarkers. The levels of related enzymes including LCAT, sPLA2, EPT1 and ACER1 were detected. The results showed that "Trichosanthis Fructus-Allii Macrostemonis Bulbus" significantly reduced the areas of aortic plaque and fat vacuoles of liver in AS mice and decreased the accumulation of lipid droplets and liver coefficient. "Trichosanthis Fructus-Allii Macrostemonis Bulbus" also regulated the levels of blood lipid and inflammatory injury in the liver. The metabolites of the control group, the model group and the "Trichosanthis Fructus-Allii Macrostemonis Bulbus" group could be distinguished significantly. Fifteen potential biomarkers related to AS were discovered and preliminarily identified, seven of which could be regulated by "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in a trend of returning to normal. Metabolic pathway analysis screened out two major metabolic pathways. "Trichosanthis Fructus-Allii Macrostemonis Bulbus" obviously regulated the levels of LCAT, sPLA2, EPT1 and ACER1. It was inferred that "Trichosanthis Fructus-Allii Macrostemonis Bulbus" could play a major role in AS treatment by regulating glycerophospholipid and sphingolipid metabolism disorders in the liver, with the mechanism probably relating to the intervention of the expression of LCAT, sPLA2, EPT1 and ACER1.

Colorectal cancer incidence and mortality: the current status, temporal trends and their attributable risk factors in 60 countries in 2000-2019 / 中华医学杂志(英文版)

BACKGROUND@#Globally, colorectal cancer (CRC) imposes a substantial burden on healthcare systems and confers considerable medical expenditures. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of CRC.@*METHODS@#We used data from the GLOBOCAN database to estimate CRC incidence and mortality worldwide in 2020 and their association with the human development index (HDI). Trends of age-standardized rates of incidence and mortality in 60 countries (2000-2019) were evaluated by Joinpoint regression analysis using data of Global Burden of Disease 2019. The association between exposure to country-level lifestyle, metabolic and socioeconomic factors obtained from the World Health Organization Global Health Observatory and World Bank DataBank data and CRC incidence and mortality was determined by multivariable linear regression.@*RESULTS@#CRC incidence and mortality varied greatly in the 60 selected countries, and much higher incidence and mortality were observed in countries with higher HDIs, and vice versa. From 2000 to 2019, significant increases of incidence and mortality were observed for 33 countries (average annual percent changes [AAPCs], 0.24-3.82) and 18 countries (AAPCs, 0.41-2.22), respectively. A stronger increase in incidence was observed among males (AAPCs, 0.36-4.54) and individuals <50 years (AAPCs, 0.56-3.86). Notably, 15 countries showed significant decreases in both incidence (AAPCs, -0.24 to -2.19) and mortality (AAPCs, -0.84 to -2.74). A significant increase of incidence among individuals <50 years was observed in 30 countries (AAPCs, 0.28-3.62). Countries with higher incidence were more likely to have a higher prevalence of alcohol drinking, higher level of cholesterol level, higher level of unemployment, and a poorer healthcare system.@*CONCLUSIONS@#Some high-HDI countries showed decreasing trends in CRC incidence and mortality, whereas developing countries that previously had low disease burden showed significantly increased incidence and mortality trends, especially in males and populations ≥50 years, which require targeted preventive health programs.

Clinical Characteristics and Prognosis of Elderly Patients with Medium and High risk Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and prognosis of patients with medium and high risk myelodysplastic syndrome (MDS).@*METHODS@#97 MDS patients above the age of 60 treated in Nanfang Hospital, Southern Medical University from February 2011 to August 2020 were enrolled. The clinical characteristics and prognosis of the MDS patients with medium risk, high risk or very high risk based on IPSS-R category were retrospectively analyzed. According to the difference of treatment regimes, the patients were divided into the transplantation group, chemotherapy group and other treatment group, and the efficacy among the patients in the 3 groups were analyzed.@*RESULTS@#MDS with excess blast (MDS-EB) in the elderly patients with medium and high risk MDS were the most common, 47.4% of the patients with abnormal chromosome karyotypes, and 23.7% with complex karyotypes (≥3). 97.3% of the patients showed at least one gene mutation, and TP53 mutations were detected in nearly 20% of the patients with medium and high risk. Multivariate analysis showed that IPSS-R category and treatment regimes were the factors affecting the prognosis of elderly patients with medium and high risk MDS. The median overall survival (OS) time of the patients in the 3 groups showed significant difference (P=0.012), and the median OS of the patients in the transplantation group was significantly longer than that in the chemotherapy group and other group (P=0.003,P=0.014,respectively), while there was no significant difference in median OS between chemotherapy group and other treatment group (P=0.685).@*CONCLUSION@#Elderly MDS patients with medium and high risk can benefit from allogeneic hematopoietic stem cell transplantation, which will prolong their OS.

Clinical Characteristics and Prognosis of AJCC 8th Edition Stage Ⅲ Gallbladder Cancer with Different Subtypes: A Study Based on SEER Database / 肿瘤防治研究

Objective To investigate the clinical characteristics, treatment and prognosis of the eighth edition of AJCC stage Ⅲ gallbladder cancer (GBC). Methods We collected the clinical data and follow-up results of 3485 patients with AJCC 8th stage Ⅲ gallbladder cancer. Kaplan Meier survival curves of ⅢA and ⅢB, T3N0M0 (ⅢA), T1-2N1M0 (ⅢB) and T3N1M0 (ⅢB) were drawn and compared. Single factor analysis and Cox multiple factor regression analysis were used to analyze the relation between clinical characteristics, treatment plan, stage Ⅲ subtype and prognosis. Results One-year survival rate of stage ⅢB gallbladder cancer patients was 49.70%, higher than those of stage ⅢA(36.41%); the 1-year survival rate of stage T1-2N1M0 (ⅢB) gallbladder cancer patients was 65.52%, higher than those of stage T3N0M0 (ⅢA) (36.41%) and stage T3N1M0 (ⅢB) (37.05%). According to Cox multivariate analysis, age, tumor grade, tumor size, operation mode, radiotherapy, chemotherapy, AJCC 8th TNM specific subtype and T stage were independent related factors affecting the prognosis of stage Ⅲ GBC patients (P < 0.01). Conclusion The overall survival of stage ⅢB GBC is better than that of stage ⅢA. The risk of stage Ⅲ GBC death was T1-2N1M0 (ⅢB) < T3N0M0 (ⅢA) < T3N1M0 (ⅢB). Radical cholecystectomy (number of dissected lymph node≥6), radiotherapy and chemotherapy are beneficial to the improvement of prognosis of stage Ⅲ GBC patients.

Paeonol attenuated vascular fibrosis through regulating Treg/Th17 balance in gut microbiota-dependent manner / 中国药理学与毒理学杂志

OBJECTIVE Atherosclerosis (AS) is a chronic inflammatory disease characterized by the accumulation of lipids, vascular fibrosis, and inflammation. Paeonol (Pae) is a natural phenolic compounds isolated from a traditional Chinese medicine, Cortex Moutan, which exhibits anti-AS effects. Our previous work demonstrated that gut microbiota plays an important role during AS treatment as it affects the efficacy of Pae. However, the mechanism of Pae in protect?ing against vascular fibrosis as related to gut microbiota has yet to be elucidated. To investigate the anti-fibrosis effect of Pae on AS mice and demonstrate the underlying gut microbiota-dependent mechanism. METHODS ApoE-/- mice were fed with high-fat-diet (HFD) to replicate the AS model. HE and Masson staining were used to observe the plaque forma?tion and collagen deposition. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and LC-MS/MS. The frequency of immune cells in spleen were phenotyped by flow cytometry. The mRNA expression of aortic inflammatory cytokines were detected by qRT-PCR. The protein expression of LOX and fibrosis related indicators were examined by Western blotting. RESULTS Pae restricted the development of AS and collagen deposition. Notably, the anti-fibrosis effect of Pae was achieved by regulating the gut microbiota. 16S rRNA sequencing and LC-MS/MS data indicated that the relative abundance of SCFAs-producing bacteria and SCFAs production was increased. Additionally, Pae administration selectively up-regulated the frequency of regulatory T (Treg) cells as well as down-regulated the ratio of T helper type 17 (Th17) cells in the spleen of AS mice, improving the Treg/Th17 balance. In addition, as expected, Pae intervention significantly down-regulate the mRNA expression levels of pro-inflammatory cytokines IL-1β, IL-6, TNF-αand IL-17 in the aorta tissue, up-regulate the levels of anti-inflammatory factor IL-10, a marker of Treg cells. Finally, Pae's intervention in the gut microbiota resulted in the restoration of the balance of Treg/Th17, which indirectly down-regulated the protein expression level of LOX and fibrosis-related indicators (MMP-2/9 and collagenⅠ/Ⅲ). CONCLUSION Pae attenuates vascular fibrosis in a gut microbiota-dependent manner. The under?lying protective mechanism is associated with the improved Treg/Th17 balance in spleen mediated through the increased microbiota-derived SCFAs production.

The evaluation on the value of ultrasound in determination of uterine artery data in early pregnancy for predicting gestational hypertension / 中国医师进修杂志

Objective:To investigate the value of Doppler ultrasonography in the determination of uterine artery data in early pregnancy for predicting gestational hypertension.Methods:Seventy patients with gestational hypertension treated in Jiashan First People′s Hospital from March 2018 to January 2020 were selected as the case group, and 70 healthy pregnant women who received routine prenatal examinations during the same period were selected as the control group. The differences of uterine artery data and pregnancy outcomes between the two groups at 11-13 +6 weeks of pregnancy were compared, and the value of each indicator in predicting gestational hypertension were analyzedby receiver operating characteristic (ROC) curve. Results:The uterine artery resistance index (RI), pulsatility index (PI), number of bilateral notches in the case group were higher than those in the control group: 0.54 ± 0.12 vs. 0.43 ± 0.08, 0.97 ± 0.36 vs. 0.69 ± 0.31, 12.86%(9/70) vs. 1.43%(1/70), and the differences were statistically significant ( P<0.05). The neonatal weight in the case group was lower than that in the control group: (2 912.38 ± 528.07) g vs. (3 487.39 ± 416.73) g; the intrauterine growth retardation rate, asphyxia rate and preterm birth rate in the case group were higher than those in the control group: 11.43%(8/70) vs. 1.43%(1/70), 8.57%(6/70) vs. 0, 15.71%(11/70) vs. 4.29%(3/70), the differences were statistically significant ( P<0.05). The analysis of ROC curve showed that the area under the curve(AUC) of PI in predicting gestational hypertension was the highest, and when AUC was 0.798, the sensitivity and specificity of PI in predicting gestational hypertension were 81.00% and 86.00% respectively. Conclusions:The uterine artery blood flow in pregnant women with gestational hypertension has been abnormal in early pregnancy (11-13 +6 weeks). The parameters of Doppler ultrasonography is used to predict gestational hypertension, and PI showes better predictive efficacy.

Effect of Trichosanthis Fructus-Allii Macrostemonis Bulbus on Formation of Atherosclerotic Plaque in ApoE-/- Mice Based on Autophagy of Vascular Smooth Muscle / 中国实验方剂学杂志

Objective:To explore the effect of Trichosanthis Fructus-Allii Macrostemonis Bulbus medicine on the proliferation and autophagy levels of aortic plaque vascular smooth muscle cells （VSMCs） in ApoE^-/- mice with atherosclerosis （AS）. Method:A total of 40 ApoE^-/- mice were fed with high-fat diet to replicate AS animal models. They were randomly divided into model group， Trichosanthis Fructus-Allii Macrostemonis Bulbus group， rapamycin group and atorvastatin group， and 10 mice with normal diet C57BL/6J mice were the blank group. The blank group and the model groups were given normal saline by gavage， while Trichosanthis Fructus-Allii Macrostemonis Bulbus group， rapamycin group and atorvastatin group were given corresponding drugs by gavage for 8 weeks. After the experiment， the mice were sacrificed. Total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C） levels were detected by the Microplate reader， the ratio of the aortic plaque area to the total area was observed and measured by staining with aortic gross oil red O. Western blot method was used to detect the proliferation-related protein proliferating cell nuclear antigen （PCNA） and <italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMA） levels of VSMCs in the aortic media. Transmission electron microscopy was used to observe the autophagosomes of VSMCs and detect the expressions of VSMCs autophagy-related proteins Beclin-1， light chain proteinⅡ （LC3Ⅱ） and p62. Result:Compared with the model group， the Trichosanthis Fructus-Allii Macrostemonis Bulbus group showed significant reduction in the aortic lipid accumulation and plaque area of AS mice and the levels of TC， TG， LDL-C （<italic>P</italic><0.01） and increase of HDL-C （<italic>P</italic><0.05）. Trichosanthis Fructus-Allii Macrostemonis Bulbus significantly reduced the levels of proliferation-related antigens PCNA and <italic>α</italic>-SMA in aortic VSMCs （<italic>P</italic><0.01）， and inhibited the excessive proliferation of VSMCs. Trichosanthis Fructus-Allii Macrostemonis Bulbus significantly up-regulated Beclin-1 and LC3Ⅱ in aortic VSMCs protein expression， decreased p62 accumulation （<italic>P</italic><0.01）， increased the expressions of VSMCs autophagosomes， and increased the autophagy level of VSMCs. Conclusion:Trichosanthis Fructus-Allii Macrostemonis Bulbus regulates blood lipid levels in AS mice， and inhibits the excessive proliferation of aortic VSMCs and plaque formation in the aorta of AS mice. The mechanism may be related to the up-regulation of the autophagy activity of VSMCs.

Optimization of the Extraction Technology of Phenolic Acid from Amomum tsaoko / 中国药房

OBJECTIVE：To opt imize the extraction technology of phenolic acid from Amomum tsaoko . METHODS ：The extraction technology of phenolic acid from A. tsaoko was optimized by using Box-Behnken design-response surface methodology with ethanol volume fraction ，liquid-solid ratio and extraction time as factors ，using the total contents of protocatechuic acid and vanillic acid as response value. The optimizd extraction technology was vlidated. RESULTS ：The optimal extraction technology was as follows ：ethanol volume fraction 65％，liquid-solid ratio 4∶1（mL/g），extraction time 2.5 h. After 3 times of validation tests ， average total content of protocatechuic acid and vanillic acid were 12.32 mg/g（RSD＝0.26 ％，n＝3），average relative error of which with predicted value （12.63 mg/g）was 2.45％. CONCLUSIONS ：The optimal technology is stable and feasible .

A four-component combination derived from Huang-Qin Decoction significantly enhances anticancer activity of irinotecan / 中国天然药物

Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index E

In Vitro and In Vivo Antibacterial Activity of Patchouli Alcohol from Pogostemon cablin / 中国结合医学杂志

OBJECTIVE@#To investigate the antibacterial activity of patchouli alcohol (PA) against 127 bacteria strains, including the common bacteria and drug-resistant bacteria strains both in the in vitro and in vivo tests.@*METHODS@#For the in vitro trial, the antibacterial property of PA against 107 Gram-positive and 20 Gram-negative bacteria strains was screened by agar double dilution method. For the in vivo trial, specific pathogen free Kunming strain of both male and female white mice, were used to test the protective ability of PA after being injected with the median lethal dose of the tested strains.@*RESULTS@#PA possessed antibacterial activity against all the tested 127 strains. In the in vitro test, PA could inhibit both Gram-negative bacteria (25-768μg/mL) and Gram-positive bacteria (1.5-200μg/mL). Particularly, PA was active against some drug-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA). PA also exhibited in vivo anti-MRSA activity in mice via intraperitoneal injection. PA could protect mice entirely infected with MRSA at 100 and 200 mg/kg, while 80% mice injected with MRSA could be protected at a low dose of 50μg/mL.@*CONCLUSION@#PA might be a potential antibacterial drug from natural sources and might be worthy to explore its mechanism and application in further study.