Post-stroke cognitive impairment (PSCI), one of the important complications of stroke, seriously affects the quality of life of these patients. PSCI is an important cause of disease burden of stroke. In recent years, more and more evidences show that blood biomarkers are of great significance in PSCI diagnosis, and the detection of blood biomarkers is relatively simple and more suitable for clinical application. Therefore, this paper sorts out the values of 5 blood biomarkers, nerve injury marker, metabolic biomarker, inflammatory biomarker, oxidative stress marker and other biomarker, in diagnosing PSCI, to provide references for early diagnosis and intervention of PSCI.

Alzheimer's disease (AD) is the most common form of dementia in the elderly, and there is no specific treatment to stop or reverse its progression. Mild cognitive impairment (MCI) is an important entry point for early diagnosis and prevention of AD. More and more studies have explored the risk factors and biomarkers for conversion from MCI to AD, and a series of risk prediction models have been established. This article analyzes and summarizes the different predictors and risk prediction models so as to provide basis for early identifying the high-risk group of AD, managing the controllable risk factors, and providing references for the selection and improvement of these models.

[摘 要] 目的：探讨甲状腺滤泡癌（FTC）组织中程序性死亡蛋白1（PD-1）和NOD样受体蛋白3（NLRP3）的表达及其与患者临床病理特征和预后的关系。方法：收集2015年1月至2020年6月福建医科大学附属第二医院手术切除的60例FTC患者的癌和配对癌旁组织标本，采用免疫组织化学染色法检测癌及癌旁组织中PD-1和NLRP3的阳性表达率，χ²检验或者Fisher精确检验法分析PD-1和NLRP3表达与FTC患者临床病理特征的关系，Pearson相关性分析PD-1与NLRP3表达的关系，Kaplan-Meier生存和Logistic回归分析PD-1和NLRP3表达与患者预后的关系。结果：在60例FTC组织中，PD-1和NLRP3均有较高的阳性表达率（46.67%与63.33%）。PD-1表达与FTC患者肿瘤分期、肿瘤大小、血管侵犯、复发与否具有显著相关性（均P<0.05），NLRP3表达与患者肿瘤大小、血管侵犯、甲状腺外浸润以及复发具有显著相关性（均P<0.05）。PD-1与NLRP3的表达成负相关，前者与患者更好的预后相关，后者是FTC复发的独立风险因素。结论：PD-1和NLRP3在FTC组织中有较高的阳性表达率，前者与患者更好的预后相关，后者是FTC复发的独立风险因素，且两者的表达呈负相关。

Objective:To analyze drug-related problems (DRPs) of hospitalized elderly patients with limited life expectancy.Methods:A total of 261 patients aged ≥ 70 years with limited life expectancy according to the 1-year mortality prediction index, who were admitted in the geriatric ward of Peking Union Medical College Hospital from January 2015 to December 2021 were included. According to Strand system, the categories, medications and interventions of DRPs were analyzed.Results:Among 261 patients, 187 (71.6%) had 672 DRPs. The most common DRPs were related to drug safety, including 271 (40.3%) adverse drug reactions and 149 over dosages (22.2%). A total of 207 drugs were involved in DRPs, and the top 5 classes with higher frequency of DRPs were antiinfectives for systemic use(20.7%,139/672), nervous system drugs(19.4%,130/672), alimentary tract and metabolism drugs(16.5%,111/672), cardiovascular system drugs(16.1%,108/672), and blood and hemopoietic organs drugs(13.7%,92/672). The recommendations were given by pharmacists for all 672 DRPs, and 643 were accepted by physicians (95.7%). The therapy need to be adjusted in 564 recommendations and the medications need to be monitored in 108 recommendations. In recommendations of therapy adjustment, 49.6%(280/564) were related to deprescribing. The deprescribing with higher frequency included antiinfectives for systemic use(29.6%, 83/280), lipid modifying agents(7.9%,22/280) and antithrombotic agents(7.9%,22/280). Patients with severe disability had significantly higher average DRPs(2 vs. 1) and average deprescribing(1 vs. 0) than patients without severe disability( Z=-4.83, Z=-3.61, all P<0.001). Conclusion:Drug safety is the most common DRP in limited life expectancy elderly inpatients, particularly for those with severe disability.

Objective:To analyze the influencing factors of catheter-related bloodstream infection (CRBSI) in chronic renal failure (CRF) hemodialysis patients and to construct a risk prediction model.Methods:Using the convenient sampling method, a total of 90 CRF patients who underwent hemodialysis in International Medical Department of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from May 2018 to May 2021 were selected as the research objects. The gender, age, catheter placement site, catheter type, catheter retention time, catheter care times, tube sealing method, strict hand hygiene, combination with diabetes, hemoglobin, serum albumin, dialysis time, immunosuppressant and other data of the patients were analyzed. Univariate analysis and multivariate Logistic regression were used to analyze the influencing factors of CRBSI in CRF patients and a prediction model was established. Hosmer-Lemeshow (H-L) test and area under the receiver operating characteristic curve ( AUC) were used to verify the fitting effect and discrimination of the model. Results:Among the 90 CRF hemodialysis patients, 16 patients developed CRBSI, with an incidence rate of 17.78% (16/90) . The results of univariate analysis showed that age, catheter placement site, catheter type, catheter retention time, catheter nursing times, strict implementation of hand hygiene, combination with diabetes mellitus, hemoglobin, and serum albumin were the influencing factors of CRBSI in CRF patients ( P<0.05) . Multivariate Logistic regression analysis showed that femoral vein, temporary catheter, catheter retention time greater than 2 weeks, not strictly implementing hand hygiene, complicated with diabetes and serum albumin less than 30 g/L were independent risk factors for CRBSI in CRF hemodialysis patients ( P<0.05) . The H-L test results showed that the model had good goodness of fit (χ 2=7.978, P=0.436) . The receiver operating characteristic curve analysis showed that the AUC of the model was 0.889, the best cut-off value was 0.732, the sensitivity was 81.30% and the specificity was 91.90%. Conclusions:There are many risk factors for CRBSI in RF hemodialysis patients. The establishment of the early warning model is conducive to the early risk assessment of CRBSI occurrence and the formulation of countermeasures to reduce the actual incidence of CRBSI.

[摘 要] 目的： 探讨程序性死亡蛋白-配体1（programmed death ligand-1，PD-L1）和肿瘤浸润淋巴细胞（tumor-infiltrating lymphocyte, TIL）在三阴性乳腺癌（triple-negative breast cancer，TNBC）组织中的水平及其临床意义。方法：收集2015年1月至2019年1月福建医科大学附属第二医院手术切除的61例TNBC患者的癌及癌旁组织石蜡标本，用免疫组化法检测癌组织中PD-L1表达和CD8+ TIL的水平，用卡方检测方法分析TNBC组织中PD-L1和CD8+ TIL水平与患者临床病理特征及预后的关系。结果： PD-L1和CD8+ TIL在TNBC组织中的阳性率分别为63.9%（39/61）和32.8%（20/61）。PD-L1表达与TNBC患者的肿瘤大小、淋巴结转移、病理分期、复发与否有明显关联（均P<0.05），与患者的年龄、肿瘤分化程度、脉管侵犯以及Ki67表达水平无明显关联（均P>0.05）；CD8+ TIL水平与TNBC患者的肿瘤大小、肿瘤分化程度、淋巴结转移、病理分期、复发与否有明显关联（均P<0.05），与患者的年龄、脉管侵犯以及Ki67表达水平无明显关联（均P>0.05）。PD-L1和CD8+ TIL水平与患者的无进展生存期（PFS）及总生存期（OS）具有显著相关性（均P<0.05），PD-L1+或者缺乏CD8+ TIL与患者更差的PFS及OS相关（均P<0.05）。结论：TNBC组织中存在较高水平的PD-L1和CD8+ TIL，PD-L1阳性表达或缺乏CD8+ TIL与肿瘤侵袭性增加相关，也与患者更差的PFS及OS相关。

Objective:To explore the real-world effectiveness and safety of sofosbuvir-based regimen for patients with chronic hepatitis C virus (HCV) genotype 6 infection in Hainan Island.Methods:Fifty-three cases with chronic hepatitis C virus (HCV) genotype 6 infection who were initially treated with a sofosbuvir (SOF)-based regimen [sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks or sofosbuvir combined with ribavirin (SOF+RBV) for 24 weeks], followed by 24 weeks of follow-up after discontinuation of the drug from January 2018 to March 2020 were selected. The primary outcome measures were incidence of sustained virological response at 12 weeks (SVR12) after the drug withdrawal. The secondary outcome measures were adverse drug events with sustained virological response at the end of treatment and 24 weeks after the end of treatment. The occurrence of adverse events was observed during the treatment. An intragroup comparison was performed by t-test. Intention-to-treat and modified intention-to-treat analysis was used for sustained virological respons.Results:The subtype distribution of chronic hepatitis C virus (HCV) genotype 6 in 53 cases of chronic hepatitis C infection were as follows: 22 cases of type 6a, 5 cases of type 6w, 5 cases of type 6xa, 3 cases of type 6v, 2 cases of type 6e, 2 cases of type 6r, 1 case of type 6xh, and 13 cases of special virus strains with undetermined genotype. The overall sustained virological response rate at 12 weeks after the drug withdrawal was 100%. Furthermore, HCV RNA was undetectable during the treatment period (4 weeks), at the end of treatment and after the treatment (24 weeks). There were seven cases of adverse events, mainly including fatigue, anorexia, and mild anemia; however, no serious adverse events were reported.Conclusion:Sofosbuvir-based regimen combined with ribavirin or velpatasvir cannot only achieve high response rate to HCV subtype 6a, but also obtain a good sustained virological response to the rare prevalent sub-genotypes and special virus strains of HCV genotype 6, with mild adverse reactions and acceptable safety profile.

Objective:To investigate the associations between the genetic variations of apoptosis genes and the adverse events of postoperative concurrent chemoradiotherapy in patients with rectal cancer.Methods:We enrolled 362 patients with stage Ⅱ to Ⅲ rectal cancer who received concurrent chemoradiotherapy. Whole blood sample (2 ml) was collected from patient at the time of enrollment before therapy. Sequenom MassARRAY was used to detect the genotypes of 29 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight apoptosis genes, including Fas cell surface death receptor(FAS), Fas ligand(FASL), apoptotic peptidase activating factor 1(APAF1), BCL2 associated X(BAX), TNF-related apoptosis-inducing ligand(TRAIL), TNF-related apoptosis-inducing ligand receptor 1(TRAILR1), TNF-related apoptosis-inducing ligand receptor 2(TRAILR2) and caspase-7(CASP7). The associations between genotypes and adverse events of chemoradiotherapy were measured by unconditional logistic regression model.Results:Three hundred and sixty two patients were treated with total mesorectal excision surgery followed by a total radiation dose of 50 Gy applied in 25 fractions over a period of 5 weeks concurrently with daily administration of capecitabine (1 600 mg/m 2 per day, continuously for 2 weeks and taking a week off every 21-day cycle). One hundred and six patients (29.3%) had grade≥2 myelosuppression. Three SNPs associated with the risk of grade ≥2 myelosuppression included FAS rs1468063 ( OR=1.51, 95% CI: 1.07-2.15, P=0.020), APAF1 rs11296996 ( OR=0.69, 95% CI: 0.49-0.98, P=0.039) and BAX rs4645904 ( OR=0.69, 95% CI: 0.50-0.97, P=0.030). One hundred and sixty one patients (44.5%) developed grade≥2 diarrhea. Five SNPs that significantly associated with risk of grade≥2 diarrhea included APAF1 rs11296996 ( OR=1.42, 95% CI: 1.02-2.00, P=0.040), rs74619561 ( OR=2.16, 95% CI: 1.27-3.68, P=0.005), CASP7 rs12263370 ( OR=1.67, 95% CI: 1.05-2.66, P=0.029), rs12247479 ( OR=1.85, 95% CI: 1.12-3.08, P=0.017) and TRAIL rs112822654 ( OR=0.68, 95% CI: 0.48-0.96, P=0.027). The remaining SNPs were not related to the adverse events of chemoradiotherapy (all P>0.05). Grade≥2 myelosuppression occurred less frequently in male than in female ( P=0.046); Surgical treatment and tumor location had great impact on the occurrence of grade≥2 diarrhea (all P<0.001) and dermatitis (all P<0.05). Conclusions:The genetic variations of FAS, APAF1, BAX, TRAIL and CASP7 are related to the adverse events of concurrent chemoradiotherapy in patients with rectal cancer, which may be potential genetic biomarkers for individualized treatment of rectal cancer.

Objective:To investigate the associations between the genetic variations of apoptosis genes and the adverse events of postoperative concurrent chemoradiotherapy in patients with rectal cancer.Methods:We enrolled 362 patients with stage Ⅱ to Ⅲ rectal cancer who received concurrent chemoradiotherapy. Whole blood sample (2 ml) was collected from patient at the time of enrollment before therapy. Sequenom MassARRAY was used to detect the genotypes of 29 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight apoptosis genes, including Fas cell surface death receptor(FAS), Fas ligand(FASL), apoptotic peptidase activating factor 1(APAF1), BCL2 associated X(BAX), TNF-related apoptosis-inducing ligand(TRAIL), TNF-related apoptosis-inducing ligand receptor 1(TRAILR1), TNF-related apoptosis-inducing ligand receptor 2(TRAILR2) and caspase-7(CASP7). The associations between genotypes and adverse events of chemoradiotherapy were measured by unconditional logistic regression model.Results:Three hundred and sixty two patients were treated with total mesorectal excision surgery followed by a total radiation dose of 50 Gy applied in 25 fractions over a period of 5 weeks concurrently with daily administration of capecitabine (1 600 mg/m 2 per day, continuously for 2 weeks and taking a week off every 21-day cycle). One hundred and six patients (29.3%) had grade≥2 myelosuppression. Three SNPs associated with the risk of grade ≥2 myelosuppression included FAS rs1468063 ( OR=1.51, 95% CI: 1.07-2.15, P=0.020), APAF1 rs11296996 ( OR=0.69, 95% CI: 0.49-0.98, P=0.039) and BAX rs4645904 ( OR=0.69, 95% CI: 0.50-0.97, P=0.030). One hundred and sixty one patients (44.5%) developed grade≥2 diarrhea. Five SNPs that significantly associated with risk of grade≥2 diarrhea included APAF1 rs11296996 ( OR=1.42, 95% CI: 1.02-2.00, P=0.040), rs74619561 ( OR=2.16, 95% CI: 1.27-3.68, P=0.005), CASP7 rs12263370 ( OR=1.67, 95% CI: 1.05-2.66, P=0.029), rs12247479 ( OR=1.85, 95% CI: 1.12-3.08, P=0.017) and TRAIL rs112822654 ( OR=0.68, 95% CI: 0.48-0.96, P=0.027). The remaining SNPs were not related to the adverse events of chemoradiotherapy (all P>0.05). Grade≥2 myelosuppression occurred less frequently in male than in female ( P=0.046); Surgical treatment and tumor location had great impact on the occurrence of grade≥2 diarrhea (all P<0.001) and dermatitis (all P<0.05). Conclusions:The genetic variations of FAS, APAF1, BAX, TRAIL and CASP7 are related to the adverse events of concurrent chemoradiotherapy in patients with rectal cancer, which may be potential genetic biomarkers for individualized treatment of rectal cancer.

OBJECTIVE： To establish the method for content determination of total flavonoids from Combretum alfrdii， and to optimize the extraction technology of total flavonoids from C. alfrdii. METHODS： Using aluminium trichloride as， chromogenic agent， UV spectrum was adopted to determine the content of total flavonoids from C. alfrdii. Based on single factor test， ethanol volume fraction， material-liquid ratio， extraction time， extraction temperature and times were selected as investigation factors， and the content of total flavonoids was selected as response value， Plackett-Burman design was used to screen the factors that had significant influence on the content of total flavonoidsfrom C. alfrdii. Then steepest climbing test was adopted to confirm the optimum valuing range； the extraction technology of total flavonoids was optimized by Box-Behnken response methodology. RESULTS： The linear range of total flavonoids were 0.012-0.036 mg/mL （r＝0.999 9）； RSDs of precision， stability and repeatability tests were less than 3％； the recovery ranged from 92.98％ to 99.86％ （RSD＝2.71％， n＝6）. The optimal extraction technology included that 60％ ethanol， material-liquid ratio of 1 ∶ 34 （g/mL）， extracting for 3 times， lasting for 60 min， extraction temperature of 80 ℃. Under this technology， average content of total flavonoids from C. alfrdii was 2.71％ （RSD＝1.69％， n＝6）， and the relative error was 2.65％ compared with predicted value of the model （2.64％）. CONCLUSIONS： Established method is stable and reproducible， and can be used for content determination of total flavonoids from C. alfrdii. The optimized extraction method is stable and feasible.