Based on the interaction between supramolecules of traditional Chinese medicine and enterobacteria to explore the material basis of combination of Rhei Radix et Rhizoma - Coptidis Rhizoma / 药学学报

Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of Rhei Radix et Rhizoma and Coptidis Rhizoma was explored. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used to characterize the morphological differences of Rhubarb single decoction, Coptis single decoction and Rhubarb and Coptis co-decoction. An in vitro antibacterial model (E. coli, E. faecium and B. subtilis) was established to evaluate the damage effect of the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma on enterobacteria. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the changes of chemical components of single decoctions and co-decoctions. The co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma was turbid after decocting. The spherical particles of 300-400 nm were observed under SEM, and the co-decoction was more uniform and stable than that of single decoction. The interaction between supramolecules formed after the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma and enterobacteria was significantly different from that of single decoction. In the process of interaction between supramolecules and enterobacteria, the spherical state was maintained, and the medicinal ingredients in Coptidis Rhizoma or Rhei Radix et Rhizoma were blocked, which could effectively alleviate the damage to enterobacteria. This study provided a reference for subsequent studies on the regulation of intestinal flora homeostasis by the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma.

Mechanism of Fufang Congrong Yizhi Capsules in treatment of mild cognitive impairment based on network pharmacology / 中国药理学通报

Aim To predict the mechanism of Fufang Congrong Yizhi Capsules (FCYC) in the treatment of mild cognitive impairment (MCI) by network pharmacology method, and further validate it in combination with cellular experiments. Methods TCMSP, Gene-Cards, OMIM and TTD databases, Chinese Pharmacopoeia and related literature were used to screen the active ingredients of FCYC and the targets of MCI treatment. The TCM-compound-target-disease network and PPI of intersection targets were constructed, and the GO and KEGG analysis were performed by the Ehamb bioinformation platform. GO and KEGG analysis were performed through Yihanbo biological information platform. Cell model of MCI was established by PC-12 injury induced by Aβ

Resveratrol inhibits autophagy and promotes apoptosis in uveal melanoma cells via miR-512-3P/DUSPl axis / 中国药理学通报

Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L

The Harm of Shame to Self and Its Way out from the Perspective of Bioethics / 中国医学伦理学

Psychological research results confirmed that the negative impact of shame on self often causes psychological diseases, and shame does not always related to ethical value. People with serious sense of shame will lead to negative evaluation and overall negation to themselves, and the sense of shame accompanied by great pain will cause great harm to individuals. To realize the sublimation of shame, the ethical orientation of its self cognitive schema and evaluation method must be changed, from the orientation of "transforming self and reaching perfection" to the position of "caring for self and accepting imperfect self" . To tap the positive value of shame, individuals must avoid hurting themselves and then care for themselves. "The principle of not harming life" and "do not denying people’s ethical subject status" are the bottom line of the ethical value of shame.

Establishment and application of a prospective follow-up research method for acute infectious diseases in Shanghai community residents / 上海预防医学

ObjectiveTo present the exploration and application of a prospective follow-up research method for acute infectious disease surveillance based on natural community populations， using COVID-19 infection as an example， and to provide a reference for improving the infectious disease surveillance and early warning system. MethodsA multi-stage probability proportional sampling method was employed to sample residents from all communities of 16 administrative districts in Shanghai， with households as the units. A cohort for acute infectious diseases based on natural community populations was established. The baseline survey was conducted for all cohort subjects， and COVID-19 antigen test kits were distributed. From December 21， 2022 to September 30， 2023， prospective follow-up monitoring of COVID-19 antigen and nucleic acid was carried out on the study subjects on a weekly basis. The baseline characteristics and follow-up information of the cohort subjects were described. ResultsThe cohort for acute infectious diseases included a total of 12 881 subjects， comprising 6 098 males （47.3%） and 6 783 females （52.7%）. The baseline survey revealed that 35.2% （4 540/12 881） of the subjects had a history of COVID-19 infection. During the follow-up period from December 21， 2022 to September 30， 2023， the average incidence density in the cohort was 0.61/person-year， with a higher incidence density in females （0.63/person-year） compared to males （0.59/person-year）. Individuals aged 60 and above （0.64/person-year） and those with underlying health conditions （0.67/person-year） had a higher incidence density. Healthcare workers showed a notably higher incidence density （0.84/person-year） than that in other occupational groups. As of September 30， 2023， a total of 340 subjects in the cohort experienced secondary infections， with a median interval of 170 days between the first and second infections. ConclusionThis study applies cohort study method to acute infectious disease surveillance， providing crucial data support for estimating infection rates and forecasting alerts for acute infectious diseases in the community. This method can be promoted and applied as a new approach for acute infectious disease surveillance.

Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction between Voriconazole and Tacrolimus Using Physiologically-Based Pharmacokinetic Modelling

Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.

The effects of natural polysaccharide supramolecular hydrogel on bacteriostatic activity and biofilm clearance of berberine / 药学学报

Taking berberine (BBR) as an example, to study whether the supramolecular hydrogel formed by berberine and lotus root starch (Nelumbo nucifera Gaertn; LRS), a natural polysaccharide, affects the inhibition to Staphylococcus aureus and the ability of biofilm clearance. The chemical structure and rheological properties of BBR@LRS gel were characterized by infrared spectroscopy and rheometer. The in vitro release of supramolecular hydrogel was observed at pH = 1.2 and pH = 7.4. Broth dilution method and biofilm clearence experiment were used to observe the bacteriostasis and biofilm clearance respectively. Cytotoxicity test and in vitro hemolysis test were used to evaluate the biosafety preliminarily. The results showed that the LRS polysaccharide hydrogel could encapsulate BBR, and there was an interaction between them. The BBR@LRS gel had good rheological properties and biosafety, and played a role in solubility enhancement and slow release of BBR, which was stronger than BBR in inhibiting the growth of Staphylococcus aureus and clearing biofilm. This study provides reference for the effect of natural polysaccharide supramolecular hydrogels on biological functions of active components of traditional Chinese medicine.

Effect of Chorionicity， Gestational Age at Birth and Birth Weight Discordance on Neonatal Outcomes in Twin Pregnancies / 中山大学学报(医学科学版)

ObjectiveTo investigate the effect of chorionicity， gestational age at birth and birth weight discordance on neonatal outcomes in twin pregnancies. MethodsWe conducted a population-based retrospective study of monochorionic diamniotic （MCDA） twin pregnancies and dichorionic diamniotic （DCDA） twin pregnancies who were admitted in the First Affiliated Hospital， Sun Yat-sen University from January 2015 to December 2020. A total of 1504 live-born twins were included， with 386 cases in MCDA group and 1118 cases in DCDA groups， respectively. The comparison of neonatal outcomes between MCDA and DCDA twins was performed using t-test， Wilcoxon rank sum test， Chi-square test or Fisher’s exact test. Logistic regression was performed to evaluate the effects of chorionicity， gestational age at birth， birth weight discordance and sex on neonatal outcomes. There were 168 live-born twins affected by inter-twin birth weight discordance≥25%， with 96 cases in MCDA group and 72 cases in DCDA groups， respectively. Logistic regression was performed to evaluate the effects of chorionicity， gestational age at birth， birth weight light or heavy （small twin or large twin） of the twin and sex on neonatal outcomes. ResultsAmong the 1 504 newborns， gestational age at birth was lower in MCDA group compared with DCDA group （P = 0.000）， and the degree of birth weight discordance was higher in MCDA group than that of the DCDA group （P = 0.001）. Birth asphyxia， respiratory distress syndrome （RDS）， bronchopulmonary dysplasia （BPD）， and sepsis were more frequency in MCDA group compared with DCDA group （P = 0.000， P = 0.000， P = 0.000， P = 0.000）. Low gestational age at birth was an independent risk factor for birth asphyxia， RDS， BPD， sepsis， necrotizing enterocolitis （NEC）≥stageⅡ， acute kidney injury （AKI）， retinopathy of prematurity （ROP）， and neonatal death respectively （P = 0.000， P = 0.000， P = 0.000， P = 0.000， P = 0.011， P = 0.000， P = 0.000， P = 0.000）. High degree of birth weight discordance was an independent risk factor for birth asphyxia， RDS， BPD， sepsis and ROP respectively （P = 0.045， P = 0.000， P = 0.000， P = 0.004， P = 0.017 ）. Chorionicity was not an independent risk factor for neonatal morbidity and death （P > 0.05）. Among the 168 twins with birth weight discordance ≥25%， low gestational age at birth was an independent risk factor for birth asphyxia， RDS， BPD， sepsis and ROP， respectively （P = 0.000， P = 0.000， P = 0.000， P = 0.000， P = 0.000）； small twin was an independent risk factor for birth asphyxia and BPD， respectively （ P = 0.013， P = 0.001）； chorionicity was not an independent risk factor for neonatal morbidity （P > 0.05）. ConclusionChorionicity was not an independent risk factor for adverse neonatal outcome in twin births. Low gestational age at birth and high degree of birth weight discordance were independent risk factor for adverse neonatal outcome in twin births. Small twins had increased risk of adverse neonatal outcome in twins with birth weight discordance ≥25%.

Analysis of interleukin-36 expression in tears of allogeneic hematopoietic stem cell transplantation patients and its correlation with the ocular surface microenvironment / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To detect the expression of interleukin(IL)-36(α, β, γ)in tears of patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT), investigate its correlation with ocular surface microenvironment, and further analyze the relationship between its expression and ocular graft-versus-host disease(oGVHD).METHODS: Prospective study. A total of 35 patients(70 eyes)underwent allo-HSCT in the hematology department of our hospital in January 2020 were selected, and 35 healthy volunteers(70 eyes)with appropriate age and gender were selected as normal control group. The patients in the allo-HSCT group were followed up 3 times after operation once every 3mo. The subjects with postoperative ocular symptoms were divided into oGVHD and Non-oGVHD group.Ocular surface disease index(OSDI)questionnaire, Schirmer test, tear break-up time(TBUT), corneal fluorescein staining(FL), and conjunctival impression cytology(CIC)was conducted in three groups. Furthermore, the expression levels of IL-36(α,β,γ)in tears were detected by ELISA.RESULTS: In the normal control group, IL-36(α, β, γ)expression levels were 74.32±5.27, 70.02±8.43, 97.41±8.66 pg/mL, respectively; in the allo-HSCT group, IL-36(α, β, γ)baseline expression levels were 77.27±7.03, 74.53±7.53, 100.77±9.74 pg/mL, with no statistically significant differences between the two groups(t=1.648, 1.954, 1.262, all P>0.05). There were no significant differences in IL-36α, IL-36β and IL-36γ in Non-oGVHD group at different time points(P>0.05), while there were significant differences in IL-36α, IL-36β and IL-36γ in oGVHD group at different time points(P<0.05). Compared with Non-oGVHD group, the levels of IL-36α and IL-36β at different time points were significantly increased in oGVHD group(all P<0.05).IL-36(α, β, γ)of oGVHD group was positively correlated with OSDI score, FL and CIC, while it was negatively correlated with TBUT and Schirmer test(all P<0.05).CONCLUSION: Evaluation of levels of tear IL-36(α, β, γ)can be of significance in diagnosing oGVHD after allo-HSCT. IL-36(α, β, γ)is highly expressed in the tears of oGVHD patients before the onset of ocular symptoms, and it is correlated with the ocular surface parameters.

Study on the time-point distribution characteristics of the occurrence of laryngopharyngeal reflux / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the characteristics of the time-point distribution of the occurrence of laryngopharyngeal reflux (LPR) by 24-hour multichannel intraluminal impedance-pH monitoring (24 h MII-pH) and to provide guidance for the development of individualized anti-reflux strategies for LPR patients. Methods: We conducted a retrospective analysis of 24 h MII-pH data from 408 patients [339 males and 69 females, aged 23-84 (55.08±11.08) years] attending the Department of Otorhinolaryngology Head and Neck Surgery at the Sixth Medical Center of the PLA General Hospital from January 2013 to March 2020. The number of gas acid/weak-acid reflux, mixed gas-liquid acid/weak-acid reflux, liquid acid/weak-acid reflux and alkaline reflux events at different time points were recorded and statistically analyzed through SPSS 26.0 software. Results: A total of 408 patients were included. Based on the 24 h MII-pH, the total positive rate of LPR was 77.45% (316/408). The type of positive gaseous weak-acid reflux was significantly higher than the remaining types of LPR (χ2=297.12,P<0.001). Except the gaseous weak-acid reflux, the occurrence of the remaining types of LPR showed a tendency to increase after meals, especially after dinner. Liquid acid reflux events occurred mainly between after dinner and the following morning, and 47.11% (57/121) of them occurred within 3 h after dinner. There was a significant positive association between Reflux Symptom Index scores and gaseous weak-acid reflux(r=0.127,P<0.01), liquid acid reflux(r=0.205,P<0.01) and liquid weak-acid reflux(r=0.103,P<0.05)events. Conclusions: With the exception of gaseous weak-acid reflux events, the occurrence of the remaining types of LPR events has a tendency to increase after meals, especially after dinner. Gaseous weak-acid reflux events accounts for the largest proportion of all types of LPR events, but the pathogenic mechanisms of gaseous weak-acid reflux are needed to further investigate.

Pregnancy Benefit of Acupuncture on in vitro Fertilization: A Systematic Review and Meta-Analysis / 中国结合医学杂志

BACKGROUND@#Currently, more and more infertility couples are opting for combined acupuncture to improve success rate of in vitro fertilization (IVF). However, evidence from acupuncture for improving IVF pregnancy outcomes remains a matter of debate.@*OBJECTIVE@#To quantitatively summarized the evidence of the efficacy of acupuncture among women undergoing IVF by means of systematic review and meta-analysis.@*METHODS@#Four English (PubMed, Web of Science, EMBASE, and Cochrane Register of Controlled Clinical Trials) and Four Chinese databases (Wanfang Databases, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and SinoMed) were searched from database inception until July 2, 2023. Randomized controlled trials (RCTs) that evaluated the acupuncture's effects for women undergoing IVF were included. The subgroup analysis was conducted with respect to the age of participants, different acupuncture types, type of control, acupuncture timing, geographical origin of the study, whether or not repeated IVF failure, and acupuncture sessions. Sensitivity analyses were predefifined to explore the robustness of results. The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR), and the secondary outcomes were ongoing pregnancy rate and miscarriage rate. Random effects model with I2 statistics were used to quantify heterogeneity. Publication bias was estimated by funnel plots and Egger's tests.@*RESULTS@#A total of 58 eligible RCTs representing 10,968 women undergoing IVF for pregnant success were identifified. Pooled CPR and LBR showed a signifificant difference between acupuncture and control groups [69 comparisons, relative risk (RR) 1.19, 95% confifidence intervals (CI) 1.12 to 1.25, I2=0], extremely low evidence; 23 comparisons, RR 1.11, 95%CI 1.02 to 1.21, I2=14.6, low evidence, respectively). Only transcutaneous electrical acupoint stimulation showed a positive effect on both CPR (16 comparisons, RR 1.17, 95%CI 1.06 to 1.29; I2=0, moderate evidence) and LBR (9 comparisons, RR 1.20, 95%CI 1.04 to 1.37; I2=8.5, extremely low evidence). Heterogeneity across studies was found and no studies were graded as high-quality evidence.@*CONCLUSION@#Results showed that the convincing evidence levels on the associations between acupuncture and IVF pregnant outcomes were relatively low, and the varied methodological design and heterogeneity might inflfluence the fifindings. (Registration No. PROSPERO CRD42021232430).

Placebo Response among Different Types of Sham Acupuncture for Low Back Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials / 中国结合医学杂志

BACKGROUND@#Low back pain (LBP) is a prevalent and debilitating condition that poses a significant burden on healthcare systems. Acupuncture has been proposed as a promising intervention for LBP, but the evidence supporting its specific effect is insufficient, and the use of sham acupuncture as a control in clinical trials presents challenges due to variations in sham acupuncture techniques and the magnitude of the placebo effect.@*OBJECTIVE@#To investigate the magnitude of the placebo response of sham acupuncture in trials of acupuncture for nonspecific LBP, and to assess whether different types of sham acupuncture are associated with different responses.@*METHODS@#Four databases including PubMed, EMBASE, MEDLINE, and the Cochrane Library were searched through April 15, 2023, and randomized controlled trials (RCTs) were included if they randomized patients with LBP to receive acupuncture or sham acupuncture intervention. The main outcomes included the placebo response in pain intensity, back-specific function and quality of life. Placebo response was defined as the change in these outcome measures from baseline to the end of treatment. Random-effects models were used to synthesize the results, standardized mean differences (SMDs, Hedges'g) were applied to estimate the effect size.@*RESULTS@#A total of 18 RCTs with 3,321 patients were included. Sham acupuncture showed a noteworthy pooled placebo response in pain intensity in patients with LBP [SMD -1.43, 95% confidence interval (CI) -1.95 to -0.91, I2=89%]. A significant placebo response was also shown in back-specific functional status (SMD -0.49, 95% CI -0.70 to -0.29, I2=73%), but not in quality of life (SMD 0.34, 95% CI -0.20 to 0.88, I2=84%). Trials in which the sham acupuncture penetrated the skin or performed with regular needles had a significantly higher placebo response in pain intensity reduction, but other factors such as the location of sham acupuncture did not have a significant impact on the placebo response.@*CONCLUSIONS@#Sham acupuncture is associated with a large placebo response in pain intensity among patients with LBP. Researchers should also be aware that the types of sham acupuncture applied may potentially impact the evaluation of the efficacy of acupuncture. Nonetheless, considering the nature of placebo response, the effect of other contextual factors cannot be ruled out in this study. (PROSPERO registration No. CRD42022304416).

Astragali Radix-Curcumae Rhizoma combination inhibits proliferation, migration, and invasion of colon cancer HT-29 cells by regulating EMT / 中国中药杂志

This study aims to investigate the effect of Astragali Radix-Curcumae Rhizoma(AC) combination on the proliferation, migration, and invasion of colon cancer HT-29 cells based on epithelial-mesenchymal transition(EMT). HT-29 cells were respectively treated with 0, 3, 6 and 12 g·kg~(-1) AC-containing serum for 48 h. The survival and growth of cells were measured by thiazole blue(MTT) colorimetry, and the proliferation, migration, and invasion of cells were detected by 5-ethynyl-2'-deoxyuridine(EdU) test and Transwell assay. Cell apoptosis was examined by flow cytometry. The BALB/c nude mouse model of subcutaneous colon cancer xenograft was established, and then model mice were classified into blank control group, 6 g·kg~(-1) AC group, and 12 g·kg~(-1) AC group. The tumor weight and volume of mice were recorded, and the histopathological morphology of the tumor was observed based on hematoxylin-eosin(HE) staining. The expression of apoptosis-associated proteins B-cell lymphoma-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), and cleaved caspase-3, and EMT-associated proteins E-cadherin, MMP9, MMP2 and vimentin in HT-29 cells and mouse tumor tissues after the treatment of AC was determined by Western blot. The results showed that cell survival rate and the number of cells at proliferation stage decreased compared with those in the blank control group. The number of migrating and invading cells reduced and the number of apoptotic cells increased in the administration groups compared with those in the blank control group. As for the in vivo experiment, compared with the blank control group, the administration groups had small tumors with low mass and shrinkage of cells and karyopycnosis in the tumor tissue, indicating that the AC combination may improve EMT. In addition, the expression of Bcl2 and E-cadherin increased and the expression of Bax, caspase-3, cleaved caspase-3, MMP9, MMP2, and vimentin decreased in HT-29 cells and tumor tissues in each administration group. In summary, the AC combination can significantly inhibit the proliferation, invasion, migration, and EMT of HT-29 cells in vivo and in vitro and promote the apoptosis of colon cancer cells.

Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version) / 中国中药杂志

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

Mechanism of total flavonoids of Ziziphora clinopodioides in improving atherosclerosis by regulating PI3K/Akt/mTOR pathway / 中国中药杂志

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.

Clinical effect of laparoscopy for the treatment of biliary stricture after biliary dilatation operation / 中华外科杂志

Objective: To investigate the safety and effect of laparoscopy for the treatment of biliary stricture after the biliary dilatation operation. Methods: The clinical data of 78 patients,including 27 males and 51 females aged (48.6±14.2)years(range:17 to 76 years),who presented biliary stricture after biliary dilatation operation from January 2017 to June 2021 in the Department of Minimally Invasive Hepatobiliary Surgery,Hunan Provincial People's Hospital,were retrospectively collected,with 38 cases in the laparoscopy group and 40 cases in the laparotomy group. Of the 78 patients,there were 67 cases of cholangiojejunostomy stricture and 11 cases of stricture of the high intrahepatic bile duct. Statistical methods such as t-test and χ2 test were carried out to compare perioperative clinical data and follow-up information between the two groups. Results: Less intraoperative blood loss((102.6±76.4)ml vs. (162.5±105.9) ml, t=-2.874,P=0.005),shorter postoperative stay length of stay((10.5±3.7)days vs. (14.5±6.4)days, t=-3.379,P=0.001) and shorter waiting time for postoperative anal exhaust((2.0±0.6)days vs. (2.5±0.9)days, t=-2.827,P=0.006) were found in the laparoscopy group than that in the laparotomy group,with statistically significant differences. While there was no statistically difference in the operative time((252.8±54.7)minutes vs. (257.4±68.6)minutes,t=-0.331,P=0.742). Postoperative review and follow-up did not show statistically significant differences between the two groups in the residual stone rate(5.3%(2/38) vs. 5.0%(2/40)) and the incidence of recurrent biliary stricture(5.3%(2/38) vs. 7.5%(3/40))(both P>0.05). Conclusion: Laparoscopy may be safe and effective in the treatment of biliary stricture after the biliary dilatation operation,with less trauma,faster recovery compared to laparotomy.

Evaluation of uniportal video-assisted thoracoscopic decortication in treatment of drug-resistant tuberculous empyema / 中华外科杂志

Objective: To examine the safety and efficacy of the uniportal video-assisted thoracoscopic decortication in treatment of drug-resistant tuberculosis empyema. Methods: From January 2018 to December 2020, 122 cases of tuberculous empyema treated by decortication in Department of Surgery, Wuhan Pulmonary Hospital were retrospectively analyzed, including 100 males and 22 females, aged(M(IQR)) 29.5(28.0) years (range: 13 to 70 years). According to the surgical approach and drug resistance, patients with drug-resistant tuberculosis who underwent uniportal video-assisted thoracoscopic decortication were included in group A (n=22), and those who underwent thoracotomy decortication were included in group B (n=28). Drug-sensitive patients who underwent uniportal video-assisted thoracoscopic decortication were included in group C (n=72). There was no statistical difference in the baseline data of the three groups (P>0.05). The operation, early postoperative recovery, and prognosis-related indicators were compared among three groups by Kruskal-Wallis test and χ2 test by Mann-Whitney U test and Bonferroni method between groups A and B, groups A and C. Results: The intraoperative blood loss of group A, group B, and group C was 200(475) ml, 300(200) ml, and 225(300) ml, respectively. There was no significant difference in intraoperative hemorrhage (H=2.74, P=0.254) and treatment outcome (χ2=4.76, P=0.575) among the three groups. Compared with group B, the operation time of group A (302.5(187.5) minutes vs. 200.0(60.0) minutes, U=171.0, P=0.007) and postoperative pulmonary reexpansion duration (4.5(3.0) months vs. 3.0 (2.2) months, U=146.5, P=0.032) were longer, and the postoperative drainage duration (9.5(7.8) days vs. 13.0(10.0) days, U=410.0, P=0.044), and the postoperative hospitalization time (12.0(7.8) days vs. 14.5(4.8) days, U=462.2, P=0.020) were shorter. There was no significant difference in complications between group A and group B (63.6%(14/22) vs. 71.4%(20/28), χ2=0.34, P=0.558). Compared with group C, the postoperative drainage duration of group A (9.5(7.8) days vs. 7.0(4.0) days, U=543.5, P=0.031), the postoperative hospitalization time (12.0(7.8) days vs. 9.0(4.0) days, U=533.0, P=0.031) and postoperative pulmonary reexpansion duration (4.5(3.0) months vs. 3.0(2.0) months, U=961.5, P=0.001) were longer. The operation time (302.5(187.5) minutes vs. 242.5(188.8) minutes, U=670.5, P=0.278), and complications (63.6%(14/22) vs. 40.3%(29/72), χ2=3.70, P=0.054) were not different between group A and group C. Conclusions: For drug-resistant tuberculous empyema, the uniportal video-assisted thoracoscopic decortication can achieve the same good therapeutic effect as drug-sensitive tuberculous empyema, and it is as safe as thoracotomy. At the same time, it has the advantage of minimally invasive and can accelerate the early postoperative recovery of patients.

Influence of Pre-treatment Lymphocyte/Monocyte Ratio and Neutrophil/Lymphocyte Ratio on the Prognosis of Patients with Extranodal NK/T-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the influence of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with extranodal NK/T cell lymphoma (ENKTL).@*METHODS@#The clinical data of 203 patients with ENKTL admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were retrospectively analyzed. The ROC curve determined the limit values of LMR and NLR; Categorical variables were compared using a chi-square test, expressed as frequency and percentage (n,%). Continuous variables were expressed as medians and extremes and compared with the Mann-Whitney U test; Progression-free survival (PFS) and overall survival (OS) of different grouped LMR and NLR patients were analyzed using Kaplan-Meier curves and compared with log-rank tests. The COX proportional risk regression model was used to perform one-factor and multi-factor analysis of PFS and OS.@*RESULTS@#The optimal critical values of LMR and NLR were determined by the ROC curve, which were 2.60 and 3.40, respectively. LMR≤2.60 was more likely to occur in patients with bone marrow invasion (P=0.029) and higher LDH (P=0.036), while NLR≥3.40 was more likely to occur in patients with higher ECOG scores (P=0.002), higher LDH (P=0.008), higher blood glucose (P=0.024), and lower PLT (P=0.010). Kaplan-Meier survival analysis showed that PFS and OS of patients in the high LMR group were significantly better than the low LMR group, while PFS and OS in the low NLR group were significantly better than the high NLR group. The results of multivariate COX analysis showed that EBV-DNA positive (P=0.047), LMR≤2.60 (P=0.014), NLR≥3.40 (P=0.023) were independent risk factors affecting PFS in patients with ENKTL. LMR≤2.60 (P<0.001), NLR≥3.40 (P=0.048), and high β2-MG (P=0.013) were independent risk factors affecting OS in patients with ENKTL.@*CONCLUSION@#Low LMR and high NLR before treatment are associated with poor prognosis in patients with ENKTL, which also can be used as an easily testable, inexpensive, and practical prognostic indicator in the clinic.

Enzymatic Digestion Method Coupled with Artificial Intelligence Techniques in Forensic Drowning Diatom Detection / 中山大学学报(医学科学版)

ObjectiveArtificial intelligence （AI） full smear automated diatom detection technology can perform forensic pathology drowning diatom detection more quickly and efficiently than human experts.However， this technique was only used in conjunction with the strong acid digestion method， which has a low extraction rate of diatoms. In this study， we propose to use the more efficient proteinase K tissue digestion method （hereinafter referred to as enzyme digestion method） as a diatom extraction method to investigate the generalization ability and feasibility of this technique in other diatom extraction methods. MethodsLung tissues from 6 drowned cadavers were collected for proteinase K ablation and made into smears， and the smears were digitized using the digital image matrix cutting method and a diatom and background database was established accordingly.The data set was divided into training set， validation set and test set in the ratio of 3：1：1， and the convolutional neural network （CNN） models were trained， internally validated， and externally tested on the basis of ImageNet pre-training. ResultsThe results showed that the accuracy rate of the external test of the best model was 97.65 %， and the area where the model features were extracted was the area where the diatoms were located. The best CNN model in practice had a precision of more than 80 % for diatom detection of drowned corpses. ConclusionIt is shown that the AI automated diatom detection technique based on CNN model and enzymatic digestion method in combination can efficiently identify diatoms and can be used as an auxiliary method for diatom detection in drowning identification.

Effect of Yanghetang-containing Serum on Breast Cancer 4T1 Cells Based on MEK/ERK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Yanghetang （YHT） on breast cancer 4T1 cells and their mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodThe YHT-containing serum was prepared from SD rats. The rats were randomly assigned into a blank group （normal saline） and low-， medium-， and high-dose （5.8， 11.6， 23.2 g·kg-1， respectively） YHT groups. The serum containing 10% YHT in each group was mixed with 90% RMPI 1640 complete medium， and the mixture was used to interfere with the cells. Cell counting kit-8 （CCK-8） method was used to detect the proliferation of the 4T1 cells treated with YHT for 24， 48， 72 h. The apoptosis， migration， and invasion of 4T1 cells were detected by flow cytometry， scratch test， and Transwell assay， respectively. Western blot was employed to determine the expression levels of MEK1/2， phosphorylation （p）-MEK1/2， ERK1/2， p-ERK1/2， and rat sarcoma virus （RAS） protein. ResultCompared with the blank group， the intervention with YHT-containing serum for 24， 48， and 72 h had significant inhibitory effect on 4T1 cell proliferation （P<0.05， P<0.01）. After intervention with YHT-containing serum for 48 h， the apoptosis rate of cells increased （P<0.01）. Compared with the blank group， the intervention with YHT for 24 h and 48 h decreased the healing ability of cells in the scratch test （P<0.01）. The invasive ability of cells treated with the low， medium， and high-dose YHT containing serum showed a decreasing trend （P<0.01）. Compared with the blank group， YHT-containing serum did not change the expression of MEK1/2 and ERK1/2 while down-regulating the expression of p-MEK1/2， p-ERK1/2， and RAS protein （P<0.01）. ConclusionYHT can inhibit the proliferation， migration， and invasion and promote the apoptosis of breast cancer 4T1 cells. In may promote the apoptosis by inhibiting the MEK/ERK signaling pathway and down-regulating the expression of p-MEK1/2， p-ERK1/2， and RAS protein.