OBJECTIVE: To study the epidemiologic characteristics of human herpes virus (HHV) activated infection in the diseases of blood system and patients received allo-HSCT by statistically analyzing the screening results of 8 human herpes viruses (HHVs) of 4164 patients in Hebei Yanda LU Dao-Pei Hospital from 2012 to 2017. METHODS: PCR was used to screen 8 HHVs. RESULTS: Two thousand and fifty-two patients (49.28%) were HHV-positive among 4164 patients screened. Among these patients screened, the infection spectra of 8 human HHVs in hematological diseases as well as patients received allogeneic hematopoietic stem cell transplantation of totally 2994 patients were summarized as follows: the positive rate of EBV (29.49%) was the highest, that of HCMV (23.15%), HHV-6 was 18.77% and HHV-7 was 17.64%, while the remaining 4 HHVs all≤2.1%. The rate of co-infection of various HHVs was significantly higher than that of single infection of HHV among all these disease groups except familial hemophagocytic lymphohistiocytosis, for which single EBV infection was the most common. The differences of positive rates among these 8 human HHVs in hematological diseases as well as patients received allogeneic hematopoietic stem cell transplantation were statistically significant by Chi-square test of R*C tables (χ=54.99, P＜0.05). For each HHV, the differences of positive rates among the above-mentioned disease groups were also statistically significant except HHV-8 (P＜0.05). CONCLUSION The patients with various blood diseases have different activated infection spectra of HHVs. EBV, HCMV, HHV-6 and HHV-7 are most common in HHVs infection. Different HHVs infections correlate with different hematologion diseases.

Objective: To analyze the failure patterns of locoregional recurrence (LRR) and investigate the range of radiotherapy in T_1-2N₁ breast cancer patients undergoing modified radical mastectomy. Methods: From September 1997 to April 2015, 2472 women with T_1-2N₁ breast cancer after modified radical mastectomy without neoadjuvant systemic therapy were treated in our hospital. 1898 patients who did not undergo adjuvant radiotherapy were included in this study. The distribution of accumulated LRR was analyzed. The LR and RR rates were estimated by the Kaplan-Meier method, and the prognostic factors were identified in univariate analyses with Log-rank test. Multivariate analysis was performed using Cox logistic regression analysis. Results: With a median follow-up of 71.3 months (range 1.1-194.6), 164 patients had LRR, including supraclavicular/infraclavicular lymph nodes in 106(65%), chest wall in 69(42%), axilla in 39(24%) and internal mammary lymph nodes (IMNs) in 19 patients (12%). In multivariate analysis, age (>45 years vs.≤45 years), tumor location (other quadrants vs. inner quadrant), T stage (T₁ vs. T₂), the number of positive axillary lymph nodes (1 vs. 2-3), hormone receptor status (positive vs. negative) were significant prognostic factors for both LR and RR. Conclusions In patients with T_1-2N₁ breast cancer after modified radical mastectomy, the most common LRR site is supraclavicular/infraclavicular nodal region, followed by chest wall. The axillary or IMN recurrence is rare. The prognostic factors for LR and RR are similar, which indicates that supraclavicular/infraclavicular and chest wall irradiation should be considered for postmastectomy radiotherapy.

Objective: To deliver macro understanding of the latest research progress on clinical trials and approved products of cancer drugs in China in 2019. Methods: The number of clinical trials and related investigational products by domestic and foreign enterprises in 2019 were acquired in the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, while listed drugs were obtained in the China Food and Drug Administration Query System for Domestic and Imported Drug. Characteristics on stage, scope, indication of those trials, classification and mechanism of involved products, as well as listed anticancer drugs were summarized and depicted. Results: There were 474 cancer drug trials registered in China in 2019, accounting for 21.8% of the total, and 397 (83.8%) were initiated by domestic pharmaceutical enterprises. Overall, international multicenter trials accounted for 13.1%, and phase I trials accounted for 47.3%. Compared with global enterprises, the proportion of international multi-center trials initiated by domestic companies is lower (4.8% vs. 55.8%, P<0.001), and the proportion of phase I clinical trials and bioequivalence trials is higher (51.9% vs. 23.4%, 19.4% vs. 1.3%, P<0.001). An accumulative of 27 cancer types were involved for all the cancer drug trials, and lung cancer, solid tumor, and breast cancer were the most common cancer types, with 103, 95 and 49 trials, respectively. For the three cancer types unique to Chinese population, gastric, liver and esophageal cancer, the total number of initiated trials was 47. For all those trials, there were 335 cancer drug varieties, with 86.0% developed by domestic pharmaceutical enterprises, including 300 therapeutic drugs, 30 adjunctive drugs and 5 preventive drugs. In terms of mechanism, targeted drugs and immune drugs were the most popular, accounting for 74.6% and 20.3%, respectively. In addition, 17 anticancer drugs targeting on 11 cancer types were approved in China in 2019. Conclusions Clinical trials on cancer drugs in China have ushered a booming era, with large number of innovative agents represented by targeted drugs and immune drugs under clinical development or putting into clinical practice. Those local enterprises are playing more and more critical roles. Strengthening clinical research and development on Chinese unique cancer types is the key direction of future work.

Objective To investigate the clinical efficacy and prognostic factors of breast cancer patients with ipsilateral supraclavicular lymph node metastasis (ISLNM) receiving neoadjuvant chemotherapy,surgery combined with radiotherapy at diagnosis.Methods Therapeutic outcomes of 65 breast cancer patients with ISLNM treated in our hospital between 1999 and 2013 were retrospectively analyzed.All patients were pathologically diagnosed with breast cancer.They were complicated with ISLNM,without distant metastasis confirmed by pathological or imaging examinations.All patients received multi-modality therapy consisting of neoadjuvant chemotherapy,surgery and postoperative radiotherapy.KaplanMeier method was adopted to calculate the overall survival (OS),progression-free survival (PFS) and supraclavicular lymph node recurrence (SCFR).The differences between two groups were statistically analyzed by the log-rank test.Results The median follow-up time was 66 months (range:6-137 months).Five patients had SCFR after corresponding treatment.The overall 5-year SCFR,OS and PFS rates were 9.2％,71.5％ and 49.5％,respectively.Following preoperative chemotherapy,the complete response (CR) of supraclavicular lymph node was a prognostic factor affecting OS.The 5-year OS rates in patients with and without CR were 81.4％ and 53.9％ (P=O.035).The size of supraclavicular lymph node (≤ 1 cm vs.＞ 1 cm at diagnosis was a risk factor of the SCFR (0％ vs.21.0％,P=0.037) and OS rates (≤1 cm vs.＞1 cm:86.1％ vs.55.6％,P =0.001).Conclusions Breast cancer patients with ISLM at diagnosis can obtain high OS rate and excellent tumor control after undergoing multi-modality therapy consisting of preoperative chemotherapy,surgery and postoperative radiotherapy.

Objective To analyze the changes in treatment patterns,clinical characteristics,treatment outcomes and prognostic factors of ductal carcinoma in situ (DCIS).Methods Clinical data of 617 female patients admitted to our institution between 2000 and 2013 were retrospectively analyzed.KaplanMeier survival analysis was adopted to calculate the local control (LC),disease-free survival (DFS) and overall survival (OS) rates.Log-rank test was utilized to identify the prognostic factors.Results Along the number of DCIS patients was gradually increased year by year,the proportion of breast conservative surgery was also elevated.However,mastectomy remained the primary surgical method.A total of 374 patients underwent mastectomy,160 cases received breast conservative surgery plus radiotherapy and 83 underwent breast conservative surgery alone.Postoperatively,366 patients (83.6％) with positive hormone receptor received hormone therapy and 45 patients (7.3％) underwent chemotherapy.The median follow-up time was 47 months.The 5-year LC,DFS and OS rates were 98.4％,97.5％ and 98.9％,respectively.Univariate analysis demonstrated that Her-2-positive patients obtained worse OS (P=0.019).Although mastectomy group had more adverse factors compared with breast conservative surgery with or without radiotherapy groups,similar survival results were obtained among three groups.Mastectomy yielded better LC and DFS compared with breast conservative surgery alone.Conclusions DCIS patients obtain favorable clinical prognosis between the breast conservative surgery and mastectomy groups.The LC rate in the mastectomy group is better than that in the breast conservative surgery group.

Objective To evaluate the risk factors of non-sentinel lymph node (NSLN) metastasis in breast cancer patients with 1-2 positive sentinel lymph nodes and to establish a new Nomogram prediction model.Methods Clinicopathological data of breast cancer patients who were diagnosed with 1-2 positive lymph nodes and underwent axillary lymph node dissection (ALND) without neoadjuvant chemotherapy from January 2008 to December 2014 were retrospectively analyzed.Measurement data between two groups were analyzed by chi-square test.Multivariate analysis was performed by logistic regression model.The prediction accuracy of the Nomogram model was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration curves.Results A total of 270 patients were recruited in this study.Among them,87(32.2％) patients had NSLN metastases.The median age was 46 years old (21-80 years),the median number of SLNs was 4 (1-10) and the median number of axillary lymph nodes was 20(10-41).Univariate analysis demonstrated that the pathological grade,the size of SLN metastasis,the number of negative and positive SLNs were the risk factors of NSLN metastasis (P=0.001-0.045).Multivariate analysis showed that pathological grade,the number of negative and positive SLNs were independent risk factors of NSLN metastasis (P=0.000-0.041).The AUC value of Nomogram prediction model for NSLN metastasis was 0.70.The false negative rate of Nomogram was 10.5％ when the cut-off point of predictive probability was ≤ 15％.Conclusions The Nomogram is a useful prediction model for evaluating NSLN metastasis.ALND or axillary radiotherapy can be avoided for patients with a low probability of NSLN metastasis.

To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

Objective To observe the difference between continuous subcutaneous insulin infusion (CSII) at acupoint and CSII at non-acupoint in treating type 2 diabetes, for providing a novel option in selecting the insulin injection site. Method Sixty-six subjects with type 2 diabetes were randomized into a treatment group of 32 cases and a control group of 34 cases. The treatment group was intervened by CSII at acupoint, while the control group was intervened by CSII at non-acupoint. The body mass index (BMI), fasting plasma glucose (FPG), 2 h-postprandial plasma glucose (P2hPG), bedtime blood sugar, glycated hemoglobin (HbA1c), consumption of insulin, and the score of diabetes symptom grading and quantification of the two groups were compared. Result The blood sugar level, insulin consumption, HbA1c level and symptom score declined significantly after treatment in both groups (P<0.05);the BMI and initial dosage of insulin in the treatment group dropped significantly after treatment in the treatment group (P<0.05); after treatment, the BMI, FPG level, initial dosage of insulin and symptom score in the treatment group were markedly lower than those in the control group (P<0.05); there were no significant differences between the treatment group and the control group in the P2 hBG level, bedtime glucose sugar level, HbA1c level, pre-prandial insulin dose and total effective rate (P>0.05). Conclusion CSII at acupoint and at non-acupoint both can effectively improve the disease condition of type 2 diabetes. The treatment group is superior to the control group in controlling BMI and FPG, reducing the initial level of insulin, and improving the symptoms, and the treatment group presents a higher total effective rate with the increase of treatment duration compared with the control group. It is indicated that insulin infusion at abdominal acupoint has a certain advantage in the treatment of type 2 diabetes.

Objective To study the newborn screening program,morbidity,laboratory findings,gene mutations,treatment and follow-up of neonatal propionic academia (PA) in Xuzhou City.Method From September 2015 to September 2018,the blood sample of neonates from newborn screening program in Xuzhou were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) method to examine the blood acylcarnitine level.The diagnosis was confirmed by urine gas chromatography mass spectrometry (GC-MS) and gene analysis.The clinical manifestation,laboratory findings,gene analysis,treatment and prognosis were retrospectively analyzed.Result A total of 297 610 live birth infants blood samples were screened using MS/MS,and 8 cases were diagnosed with PA,with a prevalence of 1∶37 201.Among the 8 patients,7 had no clinical symptoms before the diagnosis and one already had symptoms including recurrent vomiting,drowsiness,tachypnea and hypotonia.Gene analysis revealed that 6 cases carried propionyl-CoA carboxylase α (PCCA) gene mutations and 2 cases carried propionyl-CoA carboxylase β (PCCB) gene mutations.A total of 10 types of PCCA gene mutations were detected,including 5 missense mutations,4 splicing mutations and 1 synonymous mutation,among which 7 were de-novo mutations.A total of 4 types of PCCB gene mutations were detected,including 2 missense mutations,1 frameshift duplication and 1 splicing mutation,among which 3 were de-novo mutations.1 patient died after refusing treatments.The other 7 cases showed significant decline of the blood propionyl-carnitine level,the ratio of propionyl-carnitine to acetylcarnitine,3-OH-propionate and methylcitrate level in urine after treatment.4 cases had normal growth and development,and 3 cases showed various psychomotor retardation on follow-up.Conclusion Newborn screening using LC-MS/MS method is important for early diagnosis of PA.The incidence of PA is relatively high in Xuzhou City.The major clinical manifestations of PA were neurological symptoms.The main cause is PCCA gene defects and missense mutation is most common.

Stromal interaction molecule 1 (STIM1) is a transmembrane protein of the endoplasmic reticulum (ER) , a Ca2+ transducer in ER that activates the store-operated calcium channel.Through Orai1 protein, STIM1 adjusts the intracellular and extracellular calcium concentration.This way is called a store-operated Ca2+ entry.STIM1 plays a key role in phenotypic transformation of vascular smooth muscle cells, proliferation of endothelial cells, myocardial hypertrophy and myocardial fibrosis to regulate lots of cardiovascular diseases, such as atherosclerosis, congestive heart failure and systemic hypertension.STIM1 is closely related to cardiovascular diseases through calcium signal.The research progress of STIM1 in cardiovascular diseases is mainly discussed in this article.