Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Based on the idea of multi-target drug design, taking p-aminosalicylic acid (PAS) as the parent nucleus, the unreported target molecules TM1 and TM2 were designed with PAS, isonicotinic acid and fluoroquinolone as three structural units conjugated by different linkers. Sixteen target molecules were synthesized by multi-step reaction, and their activities against Mycobacterium tuberculosis and human pathogenic bacteria were evaluated. The results showed that the anti-tuberculosis activity of TM2a was stronger than those of the assayed fluoroquinolones, while TM1a was comparable to that of clinafloxacin, the most active compound of the positive control fluoroquinolones; TM1a showed the strongest inhibitory activity to all almost tested strains, TM1b and TM2a showed very strong inhibitory activity to most strains, and TM1h/2h had strong inhibitory activity to some strains; The inhibitory activities of TM1a/1h on Staphylococcus aureus ATCC14125 are much stronger than those of fluoroquinolones, which eminently deserves further study. The hemolysis test results showed that the highly active molecules TM1a and TM2a exhibited relative safety below the concentrations of 8 and 32 μg·mL^-1, respectively. In this study, a new hybrid molecule of three molecular pharmacophores with PAS as the parent nucleus was synthesized for the first time, and some of which have highly strong antibacterial activity, which provides a new idea for the research and development of antibiotics.

Objective: To retrospectively analyze the data of Chinese patients with newly diagnosed acute promyelocytic leukemia (APL) to preliminarily discuss the clinical and cytogenetic characteristics. Methods: From February 2004 to June 2020, patients with newly diagnosed APL aged ≥ 15 years who were admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College were chosen. Clinical and laboratory features were retrospectively analyzed. Results: A total of 790 cases were included, with a male to female ratio of 1.22. The median age of the patients was 41 (15-76) years. Patients aged between 20 and 59 predominated, with 632 patients (80%) of 790 patients classified as low and intermediate risk and 158 patients (20%) of 790 patients classified as high risk. The white blood cell, platelet, and hemoglobin levels at diagnosis were 2.3 (0.1-176.1) ×10(9)/L, 29.5 (2.0-1220.8) ×10(9)/L, and 89 (15-169) g/L, respectively, and 4.8% of patients were complicated with psoriasis. The long-form type of PML-RARα was most commonly seen in APL, accounting for 58%. Both APTT extension (10.3%) and creatinine>14 mg/L (1%) are rarely seen in patients at diagnosis. Cytogenetics was performed in 715 patients with newly diagnosed APL. t (15;17) with additional chromosomal abnormalities were found in 155 patients, accounting for 21.7%; among which, +8 was most frequently seen. A complex karyotype was found in 64 (9.0%) patients. Next-generation sequencing was performed in 178 patients, and 113 mutated genes were discovered; 75 genes had an incidence rate>1%. FLT3 was the most frequently seen, which accounted for 44.9%, and 20.8% of the 178 patients present with FLT3-ITD. Conclusions: Patients aged 20-59 years are the most common group with newly diagnosed APL. No obvious difference was found in the ratio of males to females. In terms of risk stratification, patients divided into low and intermediate risk predominate. t (15;17) with additional chromosomal abnormalities accounted for 21% of 715 patients, in which +8 was most commonly seen. The long-form subtype was most frequently seen in PML-RARα-positive patients, and FLT3 was most commonly seen in the mutation spectrum of APL.
Adult ; Aged ; Chromosome Aberrations ; Cytogenetics ; Female ; Humans ; Leukemia, Promyelocytic, Acute/genetics* ; Male ; Middle Aged ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies ; Young Adult

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVE: Preliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults. METHODS: Subjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days -7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection. RESULTS: All 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU/mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed. CONCLUSION The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG.
Adult ; Antibodies, Neutralizing ; Antibodies, Viral ; Data Collection ; Humans ; Rabies/prevention & control* ; Rabies Vaccines/adverse effects* ; Rabies virus/genetics*

Objective: This study aims to survey the incidence of surgical site infection (SSI) in China and to analyze its risk factors, so as to prevent and control SSI after colorectal surgery. Methods: An observative study was conducted. Based on a program of Chinese SSI Surveillance from 2018 to 2020, the clinical data of all adult patients undergoing colorectal surgery during this time period were extracted. These included demographic characteristics and perioperative clinical parameters. Minors, pregnant women, obstetric or gynecological surgery, urological system surgery, retroperitoneal surgery, resection of superficial soft tissue masses, and mesh or other implants were excluded. A total of 2122 patients undergoing colorectal surgery from 50 hospitals were included, including 1252 males and 870 females. The median age was 63 (16) years and the median BMI was 23 (4.58) kg/m². The primary outcome was the incidence of SSI within 30 days after colorectal surgery. The secondary outcomes were mortality within 30 days postoperatively, length of ICU stays and postoperative hospital stays, and cost of hospitalization. Patients were divided into the SSI group and non-SSI group based on the occurrence of SSI. Multivariable logistic regression was performed to analyze risk factors of SSI after colorectal surgery, and subgroup analysis was conducted for open and laparoscopic surgery. Results: The incidence of SSI after colorectal surgery was 5.6% (119/2122), including 47 cases (47/119, 39.5%) with superficial incisional infections, 24 cases (24/119, 20.2%) with deep incisional infections, and 48 cases (48/119, 40.3%) with organ/space infections. The occurrence of SSI significantly increased mortality [2.5% (3/119) vs. 0.1%(3/2003), χ²=22.400, P=0.003], the length of ICU stay [0 (1) day vs. 0(0) day, U=131 339, P<0.001], postoperative hospital stay [18.5 (12.8) days vs. 9.0 (6.0) days, U=167 902, P<0.001], and medical expenses [75 000 (49 000) yuan vs. 60 000 (31 000) yuan, U=126 189, P<0.001] (P<0.05). Multivariate analysis revealed that hypertension (OR=1.782, 95%CI: 1.173-2.709, P=0.007), preoperative albumin level (OR=1.680, 95%CI: 1.089-2.592, P=0.019), a contaminated or infected incision (OR= 1.993, 95%CI: 1.076-3.689, P=0.028), emergency surgery (OR=2.067, 95%CI: 1.076-3.972, P=0.029), open surgery (OR=2.132, 95%CI: 1.396-3.255, P<0.001), and surgical duration (OR=1.804, 95%CI: 1.188-2.740, P=0.006) were risk factors for SSI, while preoperative skin preparation (OR=0.478, 95%CI: 0.310-0.737, P=0.001) was a protective factor for SSI. Subgroup analysis was performed on patients undergoing open or laparoscopic surgery. The incidence of SSI in the open surgery group was 10.2%, which was significantly higher than that in the laparoscopic or robotic group (3.5%, χ²=39.816, P<0.001). Subgroup analysis identified that a contaminated or infected incision (OR=2.168, 95%CI: 1.042-4.510, P=0.038) and surgical duration (OR=2.072, 95%CI: 1.171-3.664, P=0.012) were risk factors for SSI after open surgery, while mechanical bowel preparation (OR=0.428, 95%CI: 0.227-0.807, P=0.009) and preoperative skin preparation (OR=0.356, 95%CI: 0.199-0.634, P<0.001) were protective factors for SSI after open surgery. In laparoscopic surgery, diabetes mellitus (OR= 2.292, 95%CI: 1.138-4.617, P=0.020) and hypertension (OR=2.265, 95%CI: 1.234-4.159, P=0.008) were risk factors for SSI. Conclusions: The incidence of SSI after colorectal surgery is 5.6%. Minimally invasive surgery should be selected to reduce the occurrence of postoperative SSI. To prevent the occurrence of SSI after open surgery, skin preparation and mechanical bowel preparation should be performed before the operation, and the duration of the operation should be shortened as much as possible. In the perioperative period, care of patients with hypertension, diabetes, and contaminated or infected incisions should be given particular attention.
Adult ; Albumins ; China/epidemiology* ; Colorectal Surgery/adverse effects* ; Female ; Humans ; Hypertension/complications* ; Male ; Middle Aged ; Pregnancy ; Surgical Wound Infection/etiology*

Purpose::The proposed pathological mechanism for scar formation is controversial, and increased attention has been paid to the fatty acids (FAs) in the formation of pathological scars. Notably, FAs are known to be important in inflammation and mechanotransduction, which is closely related to scar formation. Therefore, it is necessary to clarify the roles of FA in scar formation.Methods::Hypertrophic scar and keloid formed for more than a year and without other treatment, as well as normal skin samples were obtained from patients who underwent plastic surgery. Finally, keloids ( n = 10), hypertrophic scars ( n = 10), and normal skin samples ( n = 10) were collected under informed consent. Primary dermal fibroblasts were isolated and cultured. The amount and variety of FAs were detected by lipid chromatography-mass spectrometry. Immunohistochemistry, real-time PCR, and western blotting were used to verify the expression of sterol regulatory element-binding protein-1 (SREBP1) and fatty acid synthase (FASN) in the samples and their fibroblasts. Student's t-test, ANOVA, and orthogonal partial least square discriminant analysis were performed for statistical analysis (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001). Results::Compared with full-thickness normal skin, there were 27 differential FAs in keloids and 15 differential FAs in hypertrophic scars (* p < 0.05 and variable influence on projection >1.0). The expression of SREBP1 and FASN was lower in pathological scars both at mRNA and protein levels (all* p < 0.05). However, the mRNA levels of SREBP1 (*** p = 0.0002) and FASN (*** p = 0.0021) in keloid-derived fibroblasts were higher than that in normal skin fibroblasts (NFBs), while the expression in hypertrophic scar-derived fibroblasts was lower than that in NFBs (both * p < 0.05). Whereas there was no significant difference in FASN protein expression between keloid-derived fibroblasts and NFBs ( p > 0.05). Conclusion::FAs involved in pathological scars are abnormally changed in scar formation. Thus, fatty acid-derived inflammation and de novo synthesis pathway of FA may play a key role in the formation of pathological scars.

OBJECTIVES: To evaluate curative effects of coronavirus disease 2019 (COVID-19) patients by the transfusion of other convalescent plasma. METHODS: Retrospective analysis of the clinical data of 18 patients with severe and critical COVID-19, who were hospitalized in the ICU of Xianghu Branch of the First Affiliated Hospital of Nanchang University from February 1 to March 15, 2020. Patients were subdivided into an experimental group (=6, who had transfused the plasma) and an observation group (=12, who had no plasma transfusion). Basic clinical data and prognosis indexes of these two groups were compared. Moreover, for the experimental group, the dynamic changes of blood oxygen saturation before and after the transfusion, the changes of lymphocyte absolute value 48 hours after the transfusion, and the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid were analyzed. RESULTS: There were no significant differences in age, gender, blood type and other basic clinical data between the two groups (all >0.05).There were no significant differences in ventilator machine weaning time, extracorporeal membrane oxygenation (ECMO) weaning time, body temperature recovery to normal time, and hospitalization days between these two groups (all >0.05). For the experimental group, before, during and after the convalescent plasma transfusion, the blood oxygen saturation of all 6 patients at all time (1, 6, 8, 12, 24, 36, and 48 h) was more than 90%, and there was no significant fluctuation. There were 3 patients whose absolute value of lymphocyte was increased 48 hours after the transfusion, and the remaining was decreased. There were 5 patients whose SARS-CoV-2 nucleic acid detection turned negative 48 hours after the transfusion, accounting for 83.3%. CONCLUSIONS Transfusion of convalescent plasma will not affect outcomesof COVID-19 patients, which can neutralize SARS-CoV-2 in patients and reduce the loading capacity of SARS-CoV-2.
Betacoronavirus ; Blood Component Transfusion ; China ; Coronavirus Infections ; therapy ; Humans ; Immunization, Passive ; Pandemics ; Plasma ; Pneumonia, Viral ; therapy ; Retrospective Studies