The author analyzed the characteristics of phase Ⅰ clinical trials of macromolecular drugs,the characteristics of evaluation indicators of phase Ⅰ clinical trials of macromolecular drugs,such as safety evaluation,pharmacokinetic and pharmacodynamic evaluation,and efficacy evaluation.And the control points of subjects management,management of experimental macromolecule drugs,and identified and potential risk factors of macromolecule drugs in the implementation of risk management for phase Ⅰ clinical trials of macromolecule drugs were discussed in depth based on previous clinical trial research experience.Through discussion and analysis,the author suggests that each research center can formulate risk control strategies according to the actual situation,improve the efficiency of risk control,and facilitate the smooth implementation of clinical trials and improve the quality of clinical trials.

Objective To investigate the effect of erector spinae plane block on postoperative delirium and cognitive function in elderly patients with lung cancer undergoing thoracoscopic radical surgery.Methods A total of 90 elderly patients with lung cancer underwent thoracoscopic radical surgery were selected and randomly divided into the control group and the observation group,with 45 cases in each group.The patients in the control group were given general anesthesia,while the patients in the observation group were given erector spinae plane block before general anesthesia.The vital signs at different time points,opioid dosage,number of analgesic pump compressions,incision pain visual analogue scale(VAS)score,cognitive function and postoperative delirium of patients between the two groups were compared.Results At the end of anesthesia,the mean arterial pressure(MAP)and heart rate of patients in the observation group were significantly lower than those in the control group(P<0.05).The dosage of remifentanil during operation,sufentanil during perioperative period and number of analgesia pumps compressions of patients in the observation group were significantly less than those in the control group(P<0.05).The incision pain VAS scores 6 hours,12 hours,24 hours and 48 hours after surgery of patients in the observation group were significantly lower than those in the control group(P<0.05).The scores of cognitive function 6 hours and 24 hours after surgery of patients in the observation group were significantly higher than those in the control group(P<0.05);and the incidence of delirium 6 hours and 24 hours after surgery in the control group was significantly higher than those in the observation group(P<0.05).Conclusion Erector spinae plane block can significantly relieve the perioperative pain of elderly patients with lung cancer undergoing thoracoscopic radical surgery,reduce the dosage of opioids and the incidence of postoperative delirium,improve the postoperative cognitive function of patients,which provides a new idea for reducing the incidence of postoperative mental diseases.

OBJECTIVE: To establish a prognostic nomogram based on response to bortezomib and BTK expression for treatment-experienced multiple myeloma patients. METHODS: The Oncomine database was utilized to determine BTK expression, sex, age, albumin, Mayo index, response to bortezomib treatment, follow-up time and survival status in multiple myeloma(MM) patients. Cut-off point for BTK expression was calculated using R software. Univariate and multivariate analyses by Cox proportional hazards regression were then performed. Significant prognostic factors were combined to build a nomogram. The discrimination ability and predictive accuracy of the nomogram were evaluated using the index of concordance (C-index) and calibration curves. RESULTS: Multivariate analysis showed that response to bortezomib, BTK expression and sex were independent risk factors for prognosis. The C-index value of the nomogram made according to the independent risk factors was 0.729 (95%CI, 0.642-0.8164). The calibration curves showed good consistency between predicted and actual survivals for 1-year and 2-year overall survival. CONCLUSION The proposed nomogram is accurate in predicting the prognosis of patients with MM.
Bortezomib/therapeutic use* ; Humans ; Multiple Myeloma/drug therapy* ; Nomograms ; Prognosis ; Proportional Hazards Models

Background::Single-tablet regimen (STR) provides a convenient once-daily regimen for the prevention of human immunodeficiency virus (HIV) infection. Here, we investigated the safety and tolerability of coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a three-drug, STR for post-exposure prophylaxis (PEP) in Chinese individuals.Methods::This was a prospective, open-label, single-arm trial conducted in a sexually transmitted diseases and acquired immunodeficiency syndrome clinic of a tertiary hospital in Beijing, China. Adults requiring PEP were prescribed BIC/FTC/TAF one pill once a day for 28 days. Clinical and laboratory data were collected and analyzed at baseline, weeks 2, 4, 8, 12, and 24.Results::Of 112 participants enrolled in the study, 109 (97.3%) were male and the mean age was 30 ± 8 years. PEP completion was 96.4% (95% confidence interval: 91.1-99.0%). Two participants stopped PEP after 2 days because the source partner was identified as HIV uninfected. One participant was excluded due to hepatitis B virus infection according to the exclusion criteria. One discontinued due to the participant’s decision. No participant acquired HIV through week 24. Adherence was 98.9% (standard deviation [SD]: 3.3%) by self-reporting and 98.5% (SD: 3.5%) by pill count. Only five participants experienced mild clinical adverse events attributed to the study drug (including headache, diarrhea, and nausea) and four participants had elevated serum creatinine (grade 1).Conclusions::A once daily, STR of BIC/FTC/TAF used as PEP was safe and well-tolerated with a high rate of completion and adherence in Chinese. BIC/FTC/TAF may be a good option for PEP.Trial Registration::ChiCTR.org.cn, ChiCTR2100048080

OBJECTIVE: To investigate the distribution of Chinese medicine (CM) syndrome in patients with acute myocardial infarction (AMI) on admission and its impact on prognosis. METHODS: A total of 525 AMI patients were prospectively recruited and classifified into 4 groups based on their clinical characteristics: excess-heat, excess-cold, deficiency-heat and deficiency-cold syndromes. Major adverse cardiovascular events (MACEs) were followed up. RESULTS: The excess syndrome was more common than deficiency syndrome (72.95% vs. 27.05%; P<0.05). Totally 495 (94.29%) of 525 AMI patients were followed up (median 277 days). There were 59 (11.92%) MACEs. After adjusted with confounding factors in Cox regression models, the hazard ratio (95% confifidence interval) of excess-heat, excess-cold, defificiency-heat and defificiency-cold syndrome groups were 1, 1.25 (0.63, 2.49; P<0.05), 2.37 (1.14, 4.94; P<0.05), 3.76 (1.71, 8.28; P<0.05), respectively. CONCLUSIONS Excess syndrome was more common in AMI patients and had better prognosis, while defificiency-cold syndrome had the poorest prognosis. CM syndrome was of value in predicting long-term outcomes in AMI patients.

Two male patients aged 33 and 38 years with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS)admitted in our hospital in 2016 and 2017 were reported.The main symptoms included abdominal pain and distension,numbness and weakness of the limbs.MRI showed mild ventriculomegaly with deepened sulcus and widened cerebral fissure,deepened bilateral cerebellar sulcus and the widened cleavage,atrophy of cerebellum and brainstem,and manifestations of acute cerebral infarction.Gene analysis showed mutation of mitochondrial DNA(mtDNA) A3243G.After definite diagnosis was made,patients reveived coenzyme Q10,ATP and vitamin supplements for improving circulation,and neurotrophic drugs for symptomatic treatment.The symptoms were slightly improved after treatment and two cases were followed-up as outpatients.

Strategies and techniques are extremely important to improve the evaluation efficiency and fully guarantee the consistency of dosage forms. For preparations with a structural feature as solid dosage forms and particulate dispersion systems, the structures of dosage forms are the outcome of the specific formulation and production process, which determine the drug delivery behaviors as well as the pharmacokinetics of the dosage forms. Conventional techniques failed to quantitatively determine the structures of dosage forms. Synchrotron radiation micro-computed tomography is a new generation of structural quantitative characterization technology in revealing the internal structure of dosage forms with unprecedented capability for quantitative characterization of the static and dynamic structures of dosage forms, enabling to reversely analyze the production process and identify the structure differences between the generics and brand products. Based on synchrotron radiation micro-computed tomography methodology researches and applications in static structures (powders, particulate systems, tablets, films, membranes, etc.), dynamic structures (hydration) and de-formulation of production process, we have classified the structures of dosage forms into four levels from macro-scope to molecular level as dosage forms, granular intermediates for formulation, dynamic structure and molecular structures, and proposed dosage form structure based new strategy for consistency evaluation. Along with conventional dissolution/ release behavior similarity, the internal structure consistency ensures high consistency between the brand product and the generics.

OBJECTIVETo observe the expression of urotensin II (UII) on the lung of patients with pulmonary hypertension (PH) with congenital heart disease and investigate the meaning of this phenomenon.

METHODThirty eight patients with CHD were divided into three groups according to pulmonary arterial systolic pressure (PASP) measured in cardiac catheterization and surgery: normal pulmonary pressure group (N group, PASP < 30 mm Hg, n = 10), mild PH group (M group, PASP ≥ 30 mm Hg, n = 15), severe or moderate PH group (S group, PASP ≥ 50 mm Hg, n = 13). The expression of UII protein and UII mRNA in pulmonary arterioles were measured separately by immunohistochemical (IHC) analysis and in situ hybridization (ISH) analysis.

RESULT(1) The results of UIIIHC staining: The UII protein expression of group M was higher than that of group N (20.22 ± 3.58 vs. 14.34 ± 2.18, P < 0.01), but less than group S (20.22 ± 3.58 vs. 28.92 ± 3.22, P < 0.05). (2) The results of UIIISH mRNA staining were similar to IHC staining, the A value of group M was higher than group N (12.51 ± 2.02 vs. 8.85 ± 1.41, P < 0.05), less than that of group S(12.51 ± 2.02 vs. 25.35 ± 4.33, P < 0.01). (3) Correlation study: there was a positive correlation between the A values of UIIIHC and pulmonary hypertension (r = 0.64, P < 0.01, n = 38), a positive correlation between the A values of UIIISH and pulmonary hypertension (r = 0.58, P < 0.01, n = 38).

CONCLUSIONThere was the expression of Urotensin II protein and mRNA in the lung of pulmonary hypertension patients with congenital heart disease, and these expression may involve the formation of pulmonary hypertension of congenital heart disease.

Adolescent ; Blood Pressure ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Heart Defects, Congenital ; complications ; metabolism ; physiopathology ; Humans ; Hypertension, Pulmonary ; etiology ; metabolism ; physiopathology ; Immunohistochemistry ; In Situ Hybridization ; Infant ; Lung ; metabolism ; physiopathology ; Male ; Pulmonary Artery ; metabolism ; physiopathology ; RNA, Messenger ; genetics ; metabolism ; Severity of Illness Index ; Urotensins ; genetics ; metabolism

Objective To analyze the disease spectrum of patients admitted to the General Internal Medicine Unit at Peking Union Medical College Hospital, which is the first academic division of general internal medicine in the department of medicine within Chinese medical colleges and universities, and the value of general internal medicine unit in comprehensive hospitals. Methods A retrospective data review of patients admitted to the General Internal Medicine Unit from 2004 to 2008 was conducted from hospital information system and partially by chart review manually. Analysis of disease spectrum was performed thereafter. Results A total of 2593 patients were included in our study. It consisted of 1075 men and 1518women, with an average age of 45.1 years old. Forty point three percent of these patients were from Beijing,the local city, and the remaining 59.7% were from outside of Beijing. Sixty-four point nine percent (1683/2593)of these patients did not have a clear diagnosis on admission, including 758 fever of unknown origin (FUO) cases and 925 non-FUO cases. The final diagnostic rate of the FUO cases was 89. 2% [676/758, with the first three leading causes as diseases of the musculoskeletal system and connective tissue (29. 8%), certain infectious and parasitic diseases(26.3%), and neoplasm (14. 5%)] . The final diagnostic rate of the 928 non-FUO cases was 86. 8%(803/925), with the first three leading causes as musculoskeletal system and connective tissue(24.9%), neoplasm (15.5%), and diseases of blood and blood-forming organs(11.4%). Despite most diagnoses fitting into the above categories, the array of diseases was broad with as many as 550 discharge diagnoses from 2004 to 2008. Conclusions During 2004 -2008, there was a high proportion of cases that presented to the General Internal Medicine Unit at Peking Union Medical College Hospital with an unclear diagnosis, and the spectrum of diseases diagnosed was very broad. This kind of patient admitting model might not only benefit patients with no clear admission diagnosis and patients with multidisciplinary medical problems for whom it is usually difficult to be admitted by a specialty unit, but would also benefit medical students and residents by providing a good clinical medicine teaching base. These features show the value of general internal unit in comprehensive hospitals.

OBJECTIVETo study the changes of serum leptin (LEP) and vascular endothelial growth factor (VEGF) in children with congenital heart disease(CHD) and their roles in CHD.

METHODSForty-eight children with acyanotic CHD (ACHD group), 20 age-matched children with cyanotic CHD (CCHD group) and 20 healthy children (control group) were enrolled. The ACHD group was subdivided into two groups with (n=20) or without concurrent heart failure (n=28). Serum LEP, VEGF, total protein and albumin levels and body mass index (BMI) were measured.

RESULTSSerum total protein and albumin levels were not apparently different in all CHD children from healthy controls, but there was a significant difference in the BMI between them (p<0.01). Serum LEP and VEGF levels and the ratio of LEP/BMI in all CHD children were significantly higher than those in healthy controls (p<0.01). Compared with the ACHD group without heart failure, the serum LEP and VEGF levels and the ratio of LEP/BMI in the CCHD and the ACHD with heart failure groups increased significantly (p<0.01). In the ACHD group, serum LEP level was positively correlated with BMI (p<0.01). In the CCHD group, there were positive correlations between serum LEP level and serum VEGF level (p<0.01) and between hemoglobin concentration and serum VEGF level (p<0.01). Arterial oxygen saturation was negatively correlated with serum VEGF (p<0.01) and LEP levels (p<0.01) in the CCHD group.

CONCLUSIONSBoth VEGF and LEP play roles in the pathophisiological process of CHD. VEGF and LEP are associated with the development of heart failure in children with ACHD.

Body Mass Index ; Child ; Child, Preschool ; Female ; Heart Defects, Congenital ; blood ; Hemoglobins ; analysis ; Humans ; Infant ; Leptin ; blood ; Male ; Oxygen ; blood ; Vascular Endothelial Growth Factor A ; blood