Transdermal microarrayed electroporation for enhanced cancer immunotherapy based on DNA vaccination.

Despite the tremendous clinical potential of nucleic acid-based vaccines, their efficacy to induce therapeutic immune response has been limited by the lack of efficient local gene delivery techniques in the human body. In this study, we develop a hydrogel-based organic electronic device (µEPO) for both transdermal delivery of nucleic acids and in vivo microarrayed cell electroporation, which is specifically oriented toward one-step transfection of DNAs in subcutaneous antigen-presenting cells (APCs) for cancer immunotherapy. The µEPO device contains an array of microneedle-shaped electrodes with pre-encapsulated dry DNAs. Upon a pressurized contact with skin tissue, the electrodes are rehydrated, electrically triggered to release DNAs, and then electroporate nearby cells, which can achieve in vivo transfection of more than 50% of the cells in the epidermal and upper dermal layer. As a proof-of-concept, the µEPO technique is employed to facilitate transdermal delivery of neoantigen genes to activate antigen-specific immune response for enhanced cancer immunotherapy based on a DNA vaccination strategy. In an ovalbumin (OVA) cancer vaccine model, we show that high-efficiency transdermal transfection of APCs with OVA-DNAs induces robust cellular and humoral immune responses, including antigen presentation and generation of IFN-γ+ cytotoxic T lymphocytes with a more than 10-fold dose sparing over existing intramuscular injection (IM) approach, and effectively inhibits tumor growth in rodent animals.

Research progress of early screening and clinical prevention services for high-risk population with cardiovascular diseases / 公共卫生与预防医学

Cardiovascular diseases are preventable and controllable, and the disease burden caused by them can be reduced after preventive intervention. Attentions should be paid to the prevention of disease causes. For high-risk population, it is necessary to conduct early screening of cardiovascular diseases, control risk factors, reduce exposure level, prevent and control the occurrence or progression of diseases. Clinical prevention services are to evaluate risk factors of health in clinical sites, which can prevent diseases by personalized intervention measures. Clinical prevention services for high-risk population with cardiovascular diseases are generally at a low level in China. This article reviews the early screening, risk factors and clinical prevention services for high-risk population with cardiovascular diseases.

Observation on the distribution of macular cone in healthy adult using adaptive optics scanning laser ophthalmoscope system / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the distribution of cone in the macular of healthy adult in different ages using adaptive optics scanning laser ophthalmoscope(AO-SLO)system, and analyze its relationship with age.METHODS: A total of 100 healthy examinees(200 eyes)in our hospital from June to July 2023 were selected, and they were divided into four groups according to their age, with 25 cases(50 eyes)in each group, including 18-30 years in group A, 31-40 years in group B, 41-50 years in group C, 51-65 years in group D. AO-SLO was performed in both eyes and cone density was measured.RESULTS: The density of cone in the foveal eccentricity of 3° and 2.4°×2.4° in each group was different(P<0.001), and the cone density in each area showed a relatively regular distribution characteristics, with the highest density in the temporal side, and the temporal>nasal>inferior>superior sides from high to low. The mean cone density in the macular area of both eyes was 14 144.38±1 082.40, 13 241.24±535.32, 12 930.29±727.73, and 10 907.50±490.86 cell/mm2, respectively(P<0.001), indicating that the cone density decreased with age. The correlation analysis showed that the mean cone density in the macular area was negatively correlated with age(r=-0.578, P<0.001).CONCLUSION: AO-SLO is a quantitative non-invasive detection of cones, and there is a negative correlation between cone density and age in healthy human. Furthermore, density of cone in healthy people over 50 years was significantly decreased.

Research progress on overweight/obesity and atherosclerosis / 公共卫生与预防医学

Overweight/obesity has become an increasingly serious global public health problem. Studies have shown that many factors caused by overweight/obesity are involved in the occurrence of atherosclerosis, including adipokines, inflammatory factors and overweight/obesity related metabolic syndrome. This paper reviews the research progress on overweight/obesity and atherosclerosis from the above perspectives, aiming to provide reference for the prevention of overweight/obesity-related atherosclerosis.

Multicopy Chromosome Integration and Deletion of Negative Global Regulators Significantly Increased the Heterologous Production of Aborycin in Streptomyces coelicolor.

Aborycin is a type I lasso peptide with a stable interlocked structure, offering a favorable framework for drug development. The aborycin biosynthetic gene cluster gul from marine sponge-associated Streptomyces sp. HNS054 was cloned and integrated into the chromosome of S. coelicolor hosts with different copies. The three-copy gul-integration strain S. coelicolor M1346::3gul showed superior production compared to the one-copy or two-copy gul-integration strains, and the total titer reached approximately 10.4 mg/L, i.e., 2.1 times that of the native strain. Then, five regulatory genes, phoU (SCO4228), wblA (SCO3579), SCO1712, orrA (SCO3008) and gntR (SCO1678), which reportedly have negative effects on secondary metabolism, were further knocked out from the M1346::3gul genome by CRISPR/Cas9 technology. While the ΔSCO1712 mutant showed a significant decrease (4.6 mg/L) and the ΔphoU mutant showed no significant improvement (12.1 mg/L) in aborycin production, the ΔwblA, ΔorrA and ΔgntR mutations significantly improved the aborycin titers to approximately 23.6 mg/L, 56.3 mg/L and 48.2 mg/L, respectively, which were among the highest heterologous yields for lasso peptides in both Escherichia coli systems and Streptomyces systems. Thus, this study provides important clues for future studies on enhancing antibiotic production in Streptomyces systems.

CdSe/TiO2NTs Heterojunction-Based Nonenzymatic Photoelectrochemical Sensor for Glucose Detection.

Compared with a single semiconductor, the heterojunction formed by two different semiconductors usually has higher light utilization and better photoelectric performance. By using stable TiO2 nanotubes as the main subject, CdSe/TiO2NTs heterojunctions were synthesized by a hydrothermal method. XRD, TEM, SEM, PL, UV-vis, and EIS were used to characterize the fabricated CdSe/TiO2NTs. Under visible light irradiation, CdSe/TiO2NTs heterojunctions exhibited a higher absorption intensity and lower degree of photogenerated carrier recombination than TiO2. The electrons and holes were proven to be effectively separated in this heterojunction via theoretical calculation. Under CdSe/TiO2NTs' optimal conditions, the glucose concentrations (10-90 µM) had a linear relationship with the photocurrent value, and the detection limit was 3.1 µM. Moreover, the CdSe/TiO2NTs sensor exhibited good selectivity and stability. Based on the experimental data and theoretical calculations, its PEC sensing mechanism was also illuminated.

The tendency of anemia of inflammation in periodontal diseases.

Anemia of inflammation (AI) is associated with inflammatory diseases, and inflammation-induced iron metabolism disorder is the major pathogenic factor. Earlier studies have reported a tendency of AI in periodontitis patients, but the explicit relationship and possible pathological mechanisms remain unclear. Here, the analyses of both periodontitis patients and a mouse model of ligature-induced experimental periodontitis showed that periodontitis was associated with lower levels of hemoglobin and hematocrit with evidence of systemic inflammation (increased white blood cell levels) and evidence of iron restriction (low serum iron along with a high serum hepcidin and ferritin levels), in accordance with the current diagnosis criteria for AI. Moreover, periodontal therapy improved the anemia status and iron metabolism disorders. Furthermore, the increased level of hepcidin and significant correlation between hepcidin and key indicators of iron metabolism emphasized the pivotal role of hepcidin in the pathogenesis of periodontitis-related AI. Administration of the signal transducer and activator of transcription 3 (STAT3) inhibitors Stattic suggested that the IL-6-STAT3-hepcidin signaling pathway participated in this regulatory process. Together, these findings demonstrated that periodontitis should be considered an inflammatory disease that contributes to the development of AI; furthermore, IL-6-STAT3-hepcidin signaling pathway plays a key regulatory role in the pathogenesis of periodontitis-related AI. Our study will provide new insights into the systemic effects of periodontitis, while meaningfully expanding the spectrum of inflammatory diseases that contribute to AI.

Research progress of FAPI PET/CT in the diagnosis of malignant liver tumors / 中华肝脏病杂志

Malignant liver tumors have a high incidence and mortality rate. Therefore, it is of great significance to promptly learn about tumor advancement status through relevant examinations for patients' follow-up, diagnosis, and therapy as well as the improvement of the five-year survival rate. The primary lesions and intrahepatic metastases of malignant liver tumors have been better demonstrated in the clinical study with the use of various isotope-labeled fibroblast activating protein inhibitors because of their low uptake in liver tissues and high tumor/background ratio, which provides a new method for early diagnosis, precise staging, and radionuclide therapy. In light of this context, a review of the research progress of fibroblast-activating protein inhibitors for the diagnosis of liver malignant tumors is presented.

Morin induces autophagy and apoptosis in hepatocellular carcinoma cells through Akt/mTOR/STAT3 pathway / 中国中药杂志

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

Neoadjuvant PD-1 Inhibitor Plus Apatinib and Chemotherapy Versus Apatinib Plus Chemotherapy in Treating Patients With Locally Advanced Gastric Cancer: A Prospective, Cohort Study

Purpose@#This study aimed to evaluate the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) inhibitors plus apatinib and chemotherapy (PAC) in patients with locally advanced gastric cancer (LAGC). @*Materials and Methods@#Seventy-three patients with resectable LAGC were enrolled and named the PAC group (n=39) or apatinib plus chemotherapy (AC) group (n=34) based on the treatment they chose. Neoadjuvant therapy was administered in a 21-day cycle for 3 consecutive cycles, after which surgery was performed. @*Results@#The PAC group exhibited a higher objective response rate than the AC group (74.4% vs. 58.8%, P=0.159). Moreover, the PAC group showed a numerically better response profile than the AC group (P=0.081). Strikingly, progression-free survival (PFS) (P=0.019) and overall survival (OS) (P=0.049) were prolonged, whereas disease-free survival (DFS) tended to be longer in the PAC group than in the AC group (P=0.056). Briefly, the 3-year PFS, DFS, and OS rates were 76.1%, 76.1%, and 86.7% in the PAC group and 46.9%, 49.9%, and 70.3% in the AC group, respectively. Furthermore, PAC (vs. AC) treatment (hazard ratio=0.286, P=0.034) was independently associated with prolonged PFS in multivariate Cox regression analyses. The incidence of adverse events did not differ between the two groups (all P>0.05), where leukopenia, anemia, hypertension, and other adverse events were commonly observed in the PAC group. @*Conclusions@#Neoadjuvant PAC therapy may achieve a preferable pathological response, delayed progression, and prolonged survival compared to AC therapy with a similar safety profile in patients with LAGC; however, further validation is warranted.

Application progress of electronic tongue on taste evaluation for drug products / 药学学报

The taste of oral dosage forms has become a critical factor affecting the drug compliance and adherence to the treatment, and clinical application of the drug product may seriously restricted due to its bad taste. On the basis of the statement for the basic principle and specific performance of existing instruments, the application progress of electronic tongue on drug taste evaluation is addressed in detail. In view of its objective, fatigue-free, less harmful and accurate advantages, electronic tongue has been widely and meaningfully applied in the aspects of bitterness masking, and quality assessment and assurance of drug products. In addition, the reasons limiting the popularization of electronic tongue are mentioned in the paper, and some suggestions might be useful to enlarge the further application in the future.

Inhibitory effect and molecular mechanism of sinomenine on human hepatocellular carcinoma HepG2 and SK-HEP-1 cells / 中国中药杂志

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

Evaluation of the predictive effect of parafoveal blood flow density of macula on the number of intravitreal Conbercept injections in patients with branch retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate blood flow density within 300μm(FD-300)around the foveal avascular zone(FAZ)in optical coherence tomography angiography(OCTA)of patients with macular edema(ME)complicated with non-ischemic branch retinal vein occlusion(BRVO), and to explore and evaluate the predictive effect of this parameter on the number of intraocular drug injections.METHODS: A retrospective case study. A total of 50 patients(50 eyes)who were diagnosed as non-ischemic BRVO combined with ME and received intravitreal conbercept(IVC)in the Affiliated Eye Hospital of Nanjing Medical University from January 2021 to March 2022 were selected, and they were treated with 3+PRN regimen. The 25 cases(25 eyes)treated with intraocular injection ≤5 times were classified as group B, and 25 cases(25 eyes)treated with intraocular injection >5 times were classified as group C, and 25 fellow eyes were randomly selected as control group A. OCTA was used to scan the macular area in 3mm×3mm to collect images of retinal blood flow, the central macular thickness(CMT)and FD-300. The CMT, best-corrected visual acuity(BCVA), and FD-300 were compared between the two groups at baseline, 1, 3, 6 and 12mo after the third injection.RESULTS: The BCVA(LogMAR)of the affected eye in both groups B and C at 1, 3, 6 and 12mo after the third injection was significantly lower than baseline(all P<0.05); the CMT and FD-300 were significantly lower than baseline(all P<0.05). Pearson correlation analysis showed that the change of BCVA(LogMAR)was positively correlated with the baseline FD-300 and CMT(group B: r=0.77, 0.70, all P<0.01; group C: r=0.89, 0.78, all P<0.01). The number of intraocular injections was negatively correlated with the baseline FD-300(group B: r=-0.63, P<0.01; group C: r=-0.71, P<0.01). Logistic regression analysis showed that the FD-300 at baseline is a factor that affects the number of intraocular drug injection.CONCLUSION: IVC can effectively alleviate macular edema of the affected eye,improve visual acuity and reduce FD-300. The eyes with worse BCVA and lower FD-300 at baseline may require more injections of anti-VEGF. Observation of FD-300 with OCTA can better predict eventual vision recovery of non-ischemic BRVO with ME before treatment.

Multimodal imaging features of dome-shaped macula with subretinal fluid in adolescents with high myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the multimodal image features of dome-shaped macula(DSM)with subretinal fluid(SRF)in adolescents with high myopia, and investigate its typical features and identification methods.METHODS: This is a retrospective study. A total of 21 adolescent patients(39 eyes)who were diagnosed as DSM in high myopic eyes with SRF in the macula area in our hospital from January 2021 to May 2022 were selected. All patients underwent color fundus photography(CFP), fundus autofluorescence(FAF), spectral-domain optical coherence tomography(SD-OCT), optical coherence tomography angiography(OCTA)and electro oculography(EOG). Among them, 18 patients(36 eyes)underwent fundus fluorescein angiography(FFA), and they were followed-up for 12mo to record the change of the central macular thickness(CMT).RESULTS: Fundus examination showed tessellated retina in affected eyes, and the deposition of granular material could be seen in the fovea of the macular area. SD-OCT showed a dome-like bulge of the whole layer in the macular area, localized detachment of the subfoveal nerve epithelial layer, the medium and high reflection attachment on the inner surface of the outer membrane, and the heterogeneous reflection of the retinal pigment epithelium(RPE)layer. FAF showed a mild “bull's eye sign” change in the macular area. FFA showed granular transmitted fluorescence around the foveal avascular zone. En face of OCTA could see a clear boundary of the neuroepithelial detachment zone. When the tangential line corresponds to the ellipsoid zone-RPE layer, the granular high reflection in different sizes scattered in the neuroepithelial detachment zone could be seen, and no obvious choroidal neovascularization(CNV)was formed. During the follow-up of OCTA, SRF in the macular area can be spontaneously increased or absorbed irregularly. EOG indicates that the ratio of light peak to dark trough(LP/DT, i.e. Arden ratio)was normal, with an Arden ratio>1.55. CMT at 1, 3, 6, 12mo(247.10±13.03, 246.62±12.23, 248.05±14.00, 247.92±11.66 μm)during follow-up period were compared with baseline(246.95±11.46 μm), and the difference was not statistically significant(F=0.144, P=0.965).CONCLUSION: Multimodal imaging is helpful in the clinical diagnosis of DSM with SRF in the macula area in high myopic eyes of adolescents, and plays an important role in the differential diagnosis of the early stage of typical Best disease.

Clinical observation of acupuncture treatment for children with accommodative myopia / 针灸推拿医学（英文版）

Objective:To observe the effect of acupuncture in the treatment of accommodative myopia in children.Methods:A total of 76 children with accommodative myopia who met the inclusion criteria were divided into a control group or a test group according to the random number table method,with 38 cases in each group.The control group was given education on eye hygiene,and the test group was treated with acupuncture twice a week for 2 months in addition to the intervention used in the control group.The patient's uncorrected visual acuity(UCVA),refraction,and axial length(AL)were measured before treatment and 1 month and 2 months after treatment.Results:After 1 month of treatment,there was no significant difference in the UCVA between the two groups(P＞0.05);after 2 months of treatment,the UCVA of the test group was better than that of the control group(P＜0.05).After 1 and 2 months of treatment,the refraction of the two groups was significantly different from that before treatment(P＜0.01),but there was no significant difference between the two groups(P＞0.05).After 1 and 2 months of treatment,the AL in the control group was increased compared with that before treatment(P＜0.05),while there was no significant change in the test group(P＞0.05),and there was no significant difference between the two groups(P＞0.05).Conclusion:Acupuncture treatment can improve UCVA in children with accommodative myopia.

A preliminary study on the effect of rapid recovery model in older adults with acute clinical conditions / 中华老年医学杂志

Objective:To explore the effectiveness of Acute Care of the Elderly(ACE)model and its existing problems in the clinical practice for older adults with acute clinical conditions.Methods:Using the random number table method, a random number sequence was generated, and the patients admitted to the Department of Geriatrics of Shenzhen Nanshan Hospital due to acute diseases From January 2019 to September 2021 were enrolled in the ACE model intervention group(160 cases)and the control group(77 cases)in a 2: 1 ratio.The inclusion criteria were based on disease severity, frailty assessment, and activity of daily living(ADL)assessment.The intervention time was 1-3 weeks.Outcomes of the patients include ADL, hospitalization days, hospitalization expenses, drug proportion, human resource investments, adverse events, 30-day readmission rate, and 1-year mortality.Results:There were no significant difference in baseline indicators such as frailty index and ADL score between the two groups at admission.The ADL score(Barthel index)of the ACE group was significantly improved compared with the control group at discharge(81.71±14.23 vs.70.9±23.89, P<0.001)and at 30 days after discharge(85.84±15.25 vs.68.29±30.91, P<0.001). The hospital cost[(12 735.81±6 541.41)￥ vs.(16 391.54±12 962.34)￥, P=0.002], drug proportion(21.34% vs.28.93 %, P=0.036)and 30-day readmission rate(13.1% vs.23.4%, P=0.037)of the ACE group were significantly lower compared to the control group.The human resource input(32.97±6.72 vs.25.03±5.31, P=0.008)and patient satisfaction(98.23% vs.90.66%, P=0.031)in the ACE group were significantly higher than those of the control group.(4)The incidence of adverse events during hospitalization was significantly lower in the ACE group than in the control group in terms of aspiration(0.63% vs.20.8%, P<0.001), falls(0 vs.10.4%, P<0.001), incontinence dermatitis(0 vs.3.9%, P=0.033), and 1-year mortality(6.3% vs.24.7%, P<0.001). There was no significant difference in the average length of stay(8.98±4.25 vs.10.03±5.32, P=0.101), pressure sores(13.01±4.77 vs.13.27±4.89, P=0.364), DVT risk score(8.53±2.79 vs.8.89±2.76, P=0.340)and medical staff satisfaction(73% vs.80%, P=0.240)between the two groups. Conclusions:The ACE model helps to reduce the disability rate of elderly patients with frailty, adverse events during hospitalization, save drug costs, and improve patient satisfaction.It is worth promoting in geriatric practice, but its localization management details and processes still face many challenges.

Exploration of critical values of monitoring indexes for perioperative major adverse cardiac events in elderly patients with biliary diseases / 中华老年医学杂志

Objective:The purpose of this study was to explore the critical values of monitored indexes of perioperative major adverse cardiac events(MACE), so as to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function to further improve the perioperative safety of elderly patients with biliary diseases.Methods:The clinical data of 246 elderly patients with biliary diseases in our hospital from May 2016 to February 2022 were collected.According to whether MACE occurred during the perioperative period, they were divided into the MACE group and the non-MACE group.The differences of clinical data, the monitoring indexes of postoperative cardiac function, and the coagulation function between the two groups were compared and analyzed.Logistic regression was used to analyze the independent risk factors of perioperative MACE, the cut-off value of the receiver operating characteristic(ROC)curve was calculated, and the Logistic multivariate prediction model was established.Results:In the MACE compared with the non-MACE group, age, postoperative complications and mortality, postoperative hospital stay, and the levels of postoperative high sensitivity troponin-I(Hs-TnI), creatine kinase isoenzyme(CK-MB), myoglobin(MYO), B-type natriuretic peptide(BNP), and D-dimer(D-D)were significantly increased(all P<0.05). Multivariate Logistic regression showed that postoperative BNP and D-D were two independent risk factors for perioperative MACE, and their cut-off values in the ROC curve were 382.65 pg/mL and 0.975mg/L respectively.The Logistic multivariate prediction model established by the Logistic regression equation was P= ex/(1+ ex), X=-5.710+ 0.003X 1+ 0.811X 2, where X 1 was the postoperative BNP level and X 2 was the postoperative D-D level.The accuracy, specificity and sensitivity of this prediction model for predicting perioperative MACE were 96.3%(237/246), 100.0%(235/235), and 18.2%(2/11). Conclusions:The Logistic multivariate prediction model established in this study can effectively predict the occurrence of perioperative MACE in elderly patients.Postoperative BNP and D-D were two independent risk factors for perioperative MACE.The cut-off values of BNP and D-D in the ROC curve could be used as critical values for monitoring perioperative MACE.Therefore, it is of great clinical significance to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function, and further improve the perioperative safety of elderly patients with biliary diseases.

Correlation between hemodynamic characteristics or dynamic cerebral autoregulation and postoperative hyperperfusion in patients undergoing carotid endarterectomy / 中华超声影像学杂志

Objective:To investigate the hemodynamic characteristics and dynamic cerebral autoregulation(dCA) of patients with severe carotid stenosis before carotid endarterectomy(CEA), and to analyze their correlations with hyperperfusion after CEA.Methods:A total of 63 patients with unilateral severe carotid artery atherosclerotic stenosis who underwent CEA were consecutively recruited prospectively in Xuanwu Hospital, Capital Medical University from January 2021 to August 2021. According to postoperative hyperperfusion, patients were divided into hyperperfusion group (13 cases) and non-hyperperfusion group (50 cases). The general clinical data and hemodynamic parameters were compared between the two groups. The dCA was evaluated by the transfer function analysis that measured the fluctuation amplitude of mean cerebral blood flow velocity(CBFV) with blood pressure change, the time difference of phase with blood pressure change, and the correlation between mean CBFV and blood pressure change. The value of dCA for predicting postoperative hyperperfusion was analyzed through the ROC curve and the area under the curve(AUC).Results:①The proportion of hypertension in hyperperfusion group was higher than that in non-hyperperfusion group ( P<0.05). ②The peak systolic velocity (PSV) at the stenosis lesion of the internal carotid artery, the end-diastolic velocity (EDV) at the stenosis lesion of the internal carotid artery and the ratio of PSV at the stenosis lesion of the internal carotid artery to the distal internal carotid artery in the hyperperfusion group were higher than the non-hyperperfusion group.And the PSV of the ipsilateral middle cerebral artery in the hyperperfusion group was lower than the non-hyperperfusion group (all P<0.05). ③In the very low-frequency and low-frequency region, the phase in the hyperperfusion group was lower than that in the non-hyperperfusion group (all P<0.05), while there was no significant difference in the high-frequency regions( P>0.05). In the three regions of very low-frequency, low-frequency and high-frequency, there were no significant differences in the gain and coherence between the two groups(all P>0.05). ④The best cutoff value of phase in the very low-frequency was 33.28 for predicting hyperperfusion after CEA (AUC=0.766, 95% CI=0.629-0.904, P=0.03), with the specificity of 0.700, and sensitivity of 0.846. Conclusions:There are differences in hemodynamics and dCA between the hyperperfusion group and the non-hyperperfusion group after CEA. The impaired preoperative dynamic cerebral autoregulation is an independent predictor of postoperative hyperperfusion.

Effect of tofacitinib combined with methotrexate on disease activity, rheumatoid factor level and morning stiffness time in patients with refractory rheumatoid arthritis / 中国医师杂志

Objective:To investigate the effect of tofacitinib combined with methotrexate on disease activity, rheumatoid factor (RF) level and morning stiffness time in patients with refractory rheumatoid arthritis (RA).Methods:A total of 120 patients with refractory RA diagnosed and treated in the First Affiliated Hospital of Hebei North University from June 2019 to June 2020 were selected as the study subjects, and they were randomly divided into three groups by random number table method: etanercept group, etanercept+ methotrexate group, and tofacitinib+ methotrexate group, with 40 patients in each group. The etanercept group was given etanercept treatment, the etanercept+ methotrexate group was given etanercept combined with methotrexate treatment, and the tofacitinib+ methotrexate group was given tofacitinib combined with methotrexate treatment. The clinical efficacy (12 W, 24 W and 48 W of treatment), disease activity, RF level, morning stiffness time and incidence of adverse reactions were compared among the three groups.Results:Comparison of the total clinical effective rate of the three groups: the total clinical effective rate of the etanercept+ methotrexate group and the tofacitinib+ methotrexate group was higher than that of the etanercept group (both P<0.05), and the tofacitinib+ methotrexate group was higher than that of the etanercept+ methotrexate group ( P<0.05). After treatment, the clinical symptoms and disease activity scores (DAS28) in the etanercept+ methotrexate and tofacitinib+ methotrexate groups were significantly improved compared with the etanercept group (all P<0.05), and the improvements in the tofacitinib+ methotrexate group were more significant than those in the etanercept+ methotrexate group ( P<0.05). After treatment, the erythrocyte sedimentation rate (ESR), RF and C-reactive protein (CRP) levels were lower in the etanercept+ methotrexate and tofacitinib+ methotrexate groups than those in the etanercept groups (all P<0.05), and the ESR, RF and CRP levels in the tofacitinib+ methotrexate groups were lower than those in the etanercept+ methotrexate group (all P<0.05). There was no significant difference in the incidence of total adverse reactions among 3 groups (7.50% vs 12.50% vs 12.50%) ( P>0.05). Conclusions:Tofacitinib combined with methotrexate can effectively improve the disease activity, RF level and morning stiffness time in patients with refractory RA, with high safety, which is worthy of clinical application and promotion.

Investigation and analysis of individual iodine nutrition among students aged 8 to 15 in Dongtai City, Jiangsu Province in 2021 / 中华地方病学杂志

Objective:To analyze the individual iodine nutrition status and its influencing factors among students aged 8 to 15 in Dongtai City, Jiangsu Province.Methods:From May to August 2021, a total of 905 students aged 8 to 15 were selected as survey subjects in Dongtai City based on the sampling method in the "National Monitoring Plan for Iodine Deficiency Disorders" (2016 version). Salt samples from students' homes were collected for salt iodine testing. Urine samples of students were collected for urinary iodine and creatinine testing. The creatinine correction method was used to estimate individual 24 h urinary iodine excretion and calculate iodine intake. At the same time, basic information (age, gender, height, weight, etc.) and consumption frequency of iodine rich foods (seafood, eggs, meat, milk, solid snacks) of students were collected through questionnaires and actual measurements.Results:The coverage rate of iodized salt in Dongtai City was 98.2% (889/905), the qualified rate of iodized salt was 97.9% (870/889), and the consumption rate of qualified iodized salt was 96.1% (870/905). The median estimated 24 h urinary iodine excretion was 179.7 μg/d. The median estimated iodine intake was 195.4 μg/d, the constituent ratio of estimated iodine intake < recommended nutrient intake (RNI) was 16.2% (147/905), RNI-tolerable upper intake level (UL) was 63.4% (574/905), and > UL was 20.3% (184/905). The medians estimated 24 h urinary iodine excretion of students aged 8-10, 11-13 and 14-15 were 157.4, 193.0 and 236.5 μg/d, respectively, and the difference was statistically significant ( H = 55.42, P < 0.001). The median estimated 24 h urinary iodine excretion of boys was higher than that of girls (222.6 vs 148.6 μg/d), and the median estimated 24 h urinary iodine excretion of urban students was higher than that of township students (215.6 vs 162.7 μg/d), the differences were statistically significant ( Z = - 8.41, - 5.66, P < 0.001). There were statistically significant differences in the median estimated 24 h urinary iodine excretion between students with different body mass index (weight loss, overweight, obesity, normal; H = 56.15, P < 0.001) and iodine rich foods consumption frequencies (seafood, meat, milk, eggs, solid snacks; H = 23.15, 21.20, 60.77, 20.01, 24.47, P < 0.001). Conclusion:Iodine deficiency or excess exists in students aged 8-15 in Dongtai City, and girls aged 8-10 who are physically emaciated are the focus of attention for iodine deficiency.