OBJECTIVE: To explore the prognosis and influencing factors of ST-segment elevation myocardial infarction (STEMI) due to late stent thrombosis (LST) and very late stent thrombosis (VLST). METHODS: Patients who underwent percutaneous coronary intervention (PCI) for STEMI caused by LST and VLST at Tianjin Chest Hospital from January 2016 to June 2021 were selected as the study subjects, and long-term follow-up was conducted. The baseline clinical features, laboratory examination indicators, echocardiography results, coronary angiography and intervention treatment characteristics, and antiplatelet treatment status of patients were collected. The study endpoint was major adverse cardiovascular event (MACE), including all-cause mortality, target vessel revascularization (TVR), myocardial infarction, and recurrent stent thrombosis (RST). Patients were divided into MACE group and non-MACE group based on the occurrence of MACE. Cox regression analysis was used to determine the univariate and multivariate predictive factors for MACE occurrence in STEMI patients caused by LST and VLST during long-term follow-up after PCI. Kaplan-Meier survival curves were plotted to analyze the cumulative survival rate without MACE during follow-up in subgroups of patients with different levels of fibrinogen (Fib) and initial number of stents. The incidence of MACE among patients receiving different drug-eluting stent (DES) treatments was compared. RESULTS: A total of 418 patients diagnosed STEMI caused by LST and VLST through coronary angiography were enrolled, of which 115 had MACE and 303 did not. Among them, 404 cases (96.65%) completed follow-up, with a median follow-up time of 27.25 (18.00, 37.00) months. Cox regression analysis showed that Fib [hazard ratio (HR) = 2.840, 95% confidence interval (95%CI) was 1.329-6.066, P = 0.007], non-culprit vascular stenosis > 50% (HR = 5.974, 95%CI was 1.634-21.848, P = 0.007), initial stent quantity (HR = 3.314, 95%CI was 1.677-6.552, P = 0.001), B2/C lesions (HR = 5.463, 95%CI was 1.396-21.373, P = 0.015), and cardiogenic shock (HR = 4.141, 95%CI was 1.101-15.568, P = 0.035) were independently associated with the occurrence of MACE. The Kaplan-Meier survival curve showed that the higher the Fib level, the lower the cumulative survival rate without MACE (82.8%, 70.1%, 40.5%, P < 0.01); the more initial stents, the lower the cumulative survival rate without MACE (75.0%, 57.7%, 36.5%), with patients with initial stents ≥ 3 having the lowest cumulative survival rate without MACE (P < 0.001). A total of 210 patients (50.2%) received secondary stent treatment, and there was no significant difference in the incidence of MACE between patients receiving first and second generation DES treatment (27.3% vs. 24.7%, P > 0.05), but patients receiving first generation DES had a higher proportion of all-cause mortality (22.3% vs. 10.1%, P < 0.05). Compared with patients receiving smaller diameter DES treatment (< 2.75 mm), patients receiving larger diameter DES treatment (≥2.75 mm) had a significantly lower incidence of MACE (20.5% vs. 35.9%, P < 0.05). CONCLUSIONS Long-term clinical outcomes after PCI for STEMI due to LST and VLST are unfavorable, with a high rate of MACE. The treatment of this particular type STEMI remains challenging, re-implantation of second generation DES or a larger diameter DES (≥2.75 mm) may be beneficial.
Humans ; Percutaneous Coronary Intervention/methods* ; ST Elevation Myocardial Infarction/therapy* ; Stents ; Prognosis ; Thrombosis/etiology* ; Female ; Male ; Coronary Angiography ; Treatment Outcome ; Risk Factors ; Middle Aged ; Drug-Eluting Stents ; Proportional Hazards Models

In order to make the shared traditional Chinese medicine （TCM） pharmacy develop more efficiently and normatively at the grass-roots level， using the “shared TCM pharmacy” as the retrieval word， this paper uses the literature research method to retrieve the reports， documents and policies from CNKI， the websites of people’s governments at all levels， the official websites of the State Administration of Traditional Chinese Medicine， people.com， China News Network， Xinhua News and other platforms before May 20， 2022， sort out the development mode and history of two “Internet plus” TCM pharmacies， namely “shared TCM pharmacies” and “smart TCM pharmacies”， and compare them with each other. Combined with the actual work of community hospitals and community service centers （stations）， the necessity and advantages （such as reducing the costs of the intermediate links of drug circulation and standardizing the grass-roots drug use process） of the development of “shared TCM pharmacy” are obtained from the perspective of primary medical care. Combined with the current situation of the promotion and application of shared TCM pharmacy in county medical communities， it is concluded that the shared TCM pharmacy should be further constructed from four aspects： improving the work process of drug centralized procurement under the background of normalization， improving the compatibility and synchronization of the whole process dispensing information system module， unifying pharmaceutical services and personnel training， defining the authority of data query and clarifying the boundaries of patient privacy to further build a shared TCM pharmacy. Finally， it integrates information technology， summarizes the definition of shared TCM pharmacy and its future construction direction， and provides reference for the next development of shared TCM pharmacy at the grass-roots level.

Abstract OBJECTIVE To establish an efficient and simple HPLC-MS/MS method for determination of flucloxacillin in newborn plasma, and to investigate the interaction between ambroxol and flucloxacillin in newborns. METHODS The samples were analyzed by API4000 HPLC-MS/MS. Ultimate XB-C18 column(2.1 mm×100 mm, 5 μm) were carried out. The mobile phase was composed of water-0.1% formic acid(A) and acetonitrile-0.1% formic acid(B). The quantitative analysis of the ion transitions were monitored at m/z 452.6→284.2 for flucloxacillin and m/z 821.4→397.3 for rifampicin(internal standard). RESULTS The linear range of flucloxacillin under this analysis method was 0.20-80 ng·mL-1, and the lower limit of quantification was 0.20 ng·mL-1; The intra-day and inter-day precision of flucloxacillin were both less than 8.23%; The extraction recovery was in the range of 85.3%-89.2%, and the matrix effect was between 89.3%-92.3%; The stability of plasma samples was good under conditions of 12 h at room temperature, 4 h at room temperature after treatment, repeated freeze-thaw for 3 times, and -20 ℃ freezing for 30 d. The results of clinical samples indicated that the combination of ambroxol could significantly increase the blood concentration of flucloxacillin. CONCLUSION The established HPLC-MS/MS method is accurate, sensitive and can be used for the determination of flucloxacillin concentration in neonatal plasma. The results of clinical samples indicate that ambroxol can significantly increase the blood concentration of flucloxacillin. There are drug interactions between ambroxol and flucloxacillin.

磷脂酰肌醇蛋白聚糖3(glypican-3，GPC3)是一种锚定在细胞膜上的硫酸乙酰肝素(heparan sulfate，HS)蛋白多糖的家族成 员之一。GPC3激活经典的Wnt/β-连环蛋白(β-catenin)途径在肝癌(hepatocellular carcinoma，HCC)中表现出促癌基因的作用。尽 管GPC3在胎肝中含量丰富，在多种实体肿瘤中高表达，然而在成人正常组织中含量极少。选择靶点是肿瘤免疫治疗的关键。迄 今为止靶向GPC3的MRI、PET和近红外成像已被用于早期HCC检测。针对GPC3+实体瘤也已经开发了各种免疫治疗方案，一种 是基于抗GPC3抗体包括单克隆抗体、多肽疫苗、免疫毒素、双特异性抗体等，一种是靶向GPC3的CAR-T/NK疗法，其中部分已 进入I/II期临床试验。靶向GPC3有可能为实体瘤治疗提供新的工具。本文概述GPC3的结构、功能等生物学特性，介绍基于抗 GPC3抗体、CAR-T细胞开发的新策略，提供GPC3免疫疗法靶向实体瘤的证据。

Objective: To investigate the expression of IFIT2 (interferon-induced protein with tetratricopeptide repeats 2) in human lung cancer tissue and analyze the relationship between the IFIT2 expression and clinicopathological features and prognosis. Methods: Tissue microarray and immunofluorescence staining were used to examine the IFIT2 expression in lung cancer tissue and their adjacent tissues. Wilcoxon rank test was used to compare the IFIT2 expression in lung cancer and corresponding adjacent tissues. The chi-square test was used to analyze the relationship between the IFIT2 expression in lung cancer tissues and clinicopathological features of the patients. Kaplan-Meier survival analysis was performed to analyze the correlation between IFIT2 expression and patients′ overall survival. Cox model was used to analyze the correlation between different clinical parameters and prognosis. Results: There was significant difference for the IFIT2 expression between the lung cancer tissues and adjacent tissues (P＜0.01). There was no significant correlation between IFIT2 expression and clinicopathological features of patients (P＞0.05). In lung adenocarcinoma and squamous cell carcinoma, Kaplan-Merier survival analysis showed that the overall survival (OS) of patients in IFIT2 low expression group was significantly shorter than that in IFIT2 high expression group (HR=2.392, 95%CI: 1.103-5.186, P=0.027; HR=2.907, 95%CI: 1.118-7.559, P=0.029, respectively). Multi-factor Cox model analysis indicated that distant metastasis (HR=8.033, 95% CI: 3.664-17.614, P=0.000) was independent prognostic factors for lung adenocarcinoma, lymph node metastasis (HR=3.390, 95% CI: 1.029-11.175, P=0.045) and IFIT2 low expression (HR=3.762,95%CI: 1.236-11.451, P=0.020) were independent prognostic factors for lung squamous cell carcinoma. Conclusion The down-regulated expression of IFIT2 in lung cancer tissues suggests that it may play an important role in initiation and development of lung cancer. It could be used as a valuable risk factor to predict the prognosis of lung cancer patients.

Objective: To investigate the effect of IFN-γ on the expression of IL-33 in colon cancer CT26 cells. Methods: CT26 cells were treated with IFN-γ and IFN-γ combined with PKA inhibitor H89, respectively, and a negative control group (NC, untreated) was set up at the same time. The mRNA expression levels of PKA, CREB and IL-33 in CT26 cells were detected by qRT-PCR. The expression levels of PKA, CREB, p-CREB and IL-33 proteins in CT26 cells were determined by western blot. The localization of CREB protein in CT26 cells was analyzed by the immunofluorescence confocal microscopy. Results: The relative expression levels of PKA, CREB and IL-33 mRNA in the IFN-γ-treated group were 2.50±0.11, 3.10±0.08 and 2.80±0.22, respectively, which were significantly higher than those in the NC group (P＜0.05). The relative expression levels of PKA, CREB and IL-33 mRNA in the IFN-γ combined with H89 treatment group were 0.21±0.02, 0.59±0.05 and 0.35±0.04, respectively, which were significantly lower than those in the NC group and IFN-γ-treated group (P＜0.05). The expression levels of PKA, CREB and IL-33 proteins detected by western blot were consistent with that of mRNA. Immunofluorescence confocal results showed that the expression level of CREB in the IFN-γ-treated group was significantly higher than that in the NC group, and that the expression level of CREB in the IFN-γ combined with H89 treatment group was significantly lower than that in the IFN-γ-treated group. Conclusion IFN-γ may induce the expression of IL-33 in colon cancer CT26 cells via the PKA-CREB pathway.

Objective To construct a prognostic nomogram for predicting the prognosis of patients with colorectal cancer ( CRC) , and verify its accuracy. Methods The clinical pathologic data from 438 CRC patients hospitalized in the Third Affiliated Hospital of Soo-chow University during January 2006 and May 2013 were retrospectively analyzed. The independent risk factors for predicting the prog-nosis of CRC were determined by the univariate and multivariate regression model. The prognostic nomogram was established by the R-language software. Then, the nomograms of postoperative 3-year and 5-year disease free survivals ( DFS) were drawn, and compared with the actual status. The internal validation and accuracy of the nomogram were determined by the Bootstrap method and the calculat-ed concordance index ( C-index) , respectively. The sensitivity and specificity of the nomogram for predicting the 3-year and 5-year DFS were compared with those of TNM system established by the American Joint Committee On Cancer (AJCC) (7th ed.) by using the time-dependent ROC curve. Results Among 438 CRC patients, the metastasis of CRC occurred in 233 patients, including 105 liver metas-tasis and 57 lung metastasis. Multivariate COX regression analysis showed that tumor differentiation degree, TNM stage, serum CEA level, serum CA19-9 level, neutrophil lymphocyte ratio ( NLR) and P53 level were the independent risk factors of CRC. The C-index of the constructed nomogram for predicting the survival rate of CRC patients was 0.678. The predicted 3-year and 5-year DFS by the no-mogram were highly coincident with the actual status. The analysis results of the time-dependent ROC curve showed that the sensitivity and specificity of the established nomogram for predicting the postoperative 3-year and 5-year DFS were higher than those of AJCC-TNM stage.Conclusion The established nomogram may accurately predict the prognosis of CRC patients, which may be helpful for clinicians to follow up or make beneficial treatment for CRC patients.

Objective: To investigate the efficacy and safety of using pegylated recombinant human granulocyte-colonystimulating factor (PEG-rhG-CSF) in preventing neutropenia in multiple chemotherapy cycles. Methods: A multicenter, prospective, open-label, singlearmstudy was designed. Patients with malignant tumors, such as lung, ovarian, and colorectal cancers, who received multiple cycles of chemotherapy with the prophylactic use of PEG-rhG-CSF for 2-4 consecutive cycles participated in the study. Results: After the prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 4.76% (13/273) in the first cycle to 1.83% (5/273), 1.15% (2/174), and 2.08% (2/96) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 11.36% (31/ 273) in the first cycle to 6.23% (17/273), 2.87% (5/174), and 3.13% (3/96) in subsequent cycles. The incidence of febrile neutropenia (FN) during the first cycle was 0.73% (2/273). The duration of FN was 2 days in one case and 5 days in another case. FN was not observed during the second, third, or fourth cycle. After the secondary prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 25% (7/28) to 3.57% (1/28), 0% (0/28), and 6.67% (1/15) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 71.43% (20/28) to 10.71% (3/28), 14.29% (4/28), and 0% (0/15) in subsequent cycles. The proportion of patients who received antibiotic therapy during the entire chemotherapy period was 10.48% (44/420). Conclusion: The application of PEG-rhG-CSF once per chemotherapy cycle can effectively reduce the occurrence of neutropenia in patients under multiple cycles of chemotherapy treatment with good safety.

Objective: To investigate the associations between various blood test parameters including MLR (monocyte-lymphocyte ratio) and prognosis in post-operative esophagogastric junction cancer patients. Methods: We retrospectively studied the preoperative and postoperative data of 309 patients who underwent radical surgery for esophagogastric junction cancer. The relationship between MLR, neutrophil lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and overall survival (OS) was analyzed. Results: The cutoff values of MLR、NLR and PLR were 0.201, 1.697 and 96.960, respectively. The median OS was 51.4 months for all the patients in the study group (n=309). MLR in patients with esophagogastric junction carcinoma was associated with gender, depth of invasion, histological grade, TNM stage, NLR and PLR (P<0.05). PLR was associated with tumor size, TNM stage, NLR and MLR (P<0.05). NLR was associated with gender, tumor size, TNM stage, PLR and MLR (both P<0.05). Univariate analysis showed that tumor size, depth of tumor invasion, metastasis of lymph nodes, pathological grading, nerve infiltration, lymphovascular invasion, TNM staging, PLR and MLR were associated with the median overall survival time (P<0.05). Multivariate analysis showed that TNM stage, nerve infiltration and MLR were independent prognostic predictors for patients with esophagogastric junction cancer (P<0.05), but not PLR or NLR. Setting the optimal cut-off value of the MLR in 0.201, the area under the curve was 0.603, significantly larger than that of PLR and NLR (P<0.05). Conclusions Preoperative MLR is a very useful predictor of patients with esophagogastric junction cancer who underwent radical rescetion. Preoperative MLR> 0.201 is an independent risk factor for postoperative survival in patients with esophagogastric cancer, and PLR> 96.960 may predict a poor prognosis risk.

The air quality of simulated moxibustion clinic was tested, which could provide references for the evaluation on air pollution in moxibustion clinic. After the clinical environment of moxibustion was established,the contents of CO,NO, PM 10 and PM 2.5 in the air at 5 different time points (0.5 h, 1 h and 2 h after 10 moxa sticks were ignited as well as 5 min ventilation after 0.5 h moxibustion burning and 5 min ventilation after 1 h moxibustion burning) were measured by testing organizations.0.5 h, 1 h and 2 h after 10 moxa sticks were ignited, the content ranges of CO,NO, PM 10 and PM 2.5 in the air were 15.9 to 37.0 mg/m,0.012 6 to 0.022 4 mg/m,0.22 to 1.28 mg/mand 0.13 to 0.53 mg/m, respectively; the contents of CO, PM 10 and PM 2.5 were higher than national standard. With 5 min ventilation after 0.5 h moxibustion burning and 5 min ventilation after 1 h moxibustion burning, the content ranges of CO,NO,PM 10 and PM 2.5 were 0.3 to 0.4 mg/m,0.015 5 to 0.018 0 mg/m,0.11 to 0.13 mg/mand 0.04 mg/m, respectively; the contents of CO, PM 10 and PM 2.5 were lower than national standard. It is concluded that long-time moxibustion could cause relatively high concentration of moxa smoke, and the contents of CO, PM 10 and PM 2.5 in the air will exceed the national standard. However, by keeping good ventilation, the contents of CO,NO,PM 10 and PM 2.5 in the air can be controlled within safe ranges.