Bufalin(BF)has a significant anti-tumor effect, but its clinical application is severely restricted by its high toxicity and poor water solubility. In this study, Scrophularia ningpoensis polysaccharide(SNP)and ursodeoxycholic acid(UDCA) were synthesized into an SNP-UDCA conjugate. BF was encapsulated to prepare BF/SNP-UDCA nanoparticles(NPs). The amphiphilic compound SNP-UDCA was synthesized via the one-step method, and its structure was characterized by Fourier-transform infrared spectroscopy(FT-IR)and proton nuclear magnetic resonance(~1H-NMR). The preparation process of BF/SNP-UDCA NPs was optimized through single-factor investigations. The encapsulation efficiency and drug-loading capacity of BF/SNP-UDCA NPs were determined by high-performance liquid chromatography(HPLC). The molecular form of BF/SNP-UDCA NPs was characterized by using a transmission electron microscope, X-ray diffraction(XRD), and differential scanning calorimeter(DSC). Additionally, the stability of BF/SNP-UDCA NPs was evaluated. The release behavior of BF/SNP-UDCA NPs at different pH values was determined by dialysis. The in vitro anti-tumor effect of BF/SNP-UDCA NPs was evaluated by MTT cytotoxicity assay, flow cytometry for apoptosis, and cellular uptake. The in vitro liver targeting was evaluated by measuring cellular uptake by laser confocal microscopy. The results demonstrated that the SNP-UDCA conjugate was successfully synthesized through an esterification reaction between SNP and UDCA. The preparation process of BF/SNP-UDCA NPs was as follows: the feed ratio of SNP-UDCA to BF was 2∶1, the ultrasonic time was 30 minutes, and the stirring time was two hours. The prepared BF/SNP-UDCA NPs were spherical in shape, with a particle size of(252.74±6.05)nm, an encapsulation efficiency of 65.00%±2.51%, and a drug-loading capacity of 6.80%±0.44%. The XRD and DSC results indicated that BF was encapsulated within the NPs and existed in a molecular or amorphous state. The short-term stability of BF/SNP-UDCA NPs and stability in DMEM medium are good, and their in vitro release behavior followed the first-order equation and was pH-dependent according to the in vitro experiment. Compared with BF, BF/SNP-UDCA NPs at the same concentration showed significantly stronger cytotoxicity and apoptotic effects on HepG2 cells(P<0.05, P<0.01). The uptake of coumarin 6(C6)/SNP-UDCA NPs in HepG2 cells was time-dependent and higher than that in HeLa cells at the same concentration of C6/SNP-UDCA NPs. Moreover, after treatment with SNP, the uptake of C6/SNP-UDCA NPs in HepG2 cells decreased. In conclusion, the preparation process of BF/SNP-UDCA NPs was simple and feasible. BF/SNP-UDCA NPs could enhance the targeting ability and inhibitory effect of BF on liver cancer cells. This study will provide a foundation for liver-targeting nanoformulations of BF.
Bufanolides/pharmacology* ; Nanoparticles/chemistry* ; Humans ; Drug Carriers/chemistry* ; Ursodeoxycholic Acid/chemistry* ; Antineoplastic Agents/pharmacology* ; Polysaccharides/chemistry* ; Scrophularia/chemistry* ; Liver Neoplasms/physiopathology* ; Hep G2 Cells

Objective To study the diagnosis,treatment,and complications of hypophosphatemic rickets(HR)in children,explore effectiveness evaluation indicators for the disease,and understand the pattern in height growth among these patients.Methods A retrospective analysis of the initial clinical data and five-year follow-up data of 85 children with HR treated at Children's Hospital of Nanjing Medical University from January 2008 to December 2022.Results Among the 85 children with HR,there were 46 males(54%)and 39 females(46%).The age at initial diagnosis ranged from 6 months to 13 years and 9 months,with a median age of 2.75 years.The average height standard deviation score was-2.0±1.1.At initial diagnosis,children exhibited reduced blood phosphate levels and elevated alkaline phosphatase(ALP),with 99%(84/85)presenting with lower limb deformities.The positive rate for PHEX gene mutations was 93%(55/59).One year post-treatment,there was a significant reduction in ALP levels and the gap between the lower limbs(P<0.05).The fastest height growth occurred in the first year after treatment,at 8.23 cm/year,with a peak height velocity(PHV)phase lasting about two years during puberty.The height increased by 9-20 cm in male children during the PHV stage and 10-15 cm in female children.Major complications included nephrocalcinosis and hyperparathyroidism.The incidence rate of nephrocalcinosis in the first year after treatment was 55%(22/40),which increased with the duration of the disease(P<0.001);an increased urinary phosphate/creatinine ratio was positively associated with a higher risk of nephrocalcinosis(OR=1.740,P<0.001).The incidence of hyperparathyroidism in the first year after treatment was 64%(27/42).Conclusions For children presenting with lower limb deformities,short stature,and slow growth,early testing for blood levels of phosphate,calcium,and ALP,along with imaging examinations of the lower limbs,can aid in the early diagnosis of HR.Genetic testing may be utilized for definitive confirmation when necessary.ALP combined with improvements in skeletal deformities and annual height growth can serve as indicators of therapeutic effectiveness for HR.Compared to normal children,children with HR demonstrate a lower height increase during the PHV phase,necessitating close follow-up and timely adjustment of treatment plans

Hypertension and osteoporosis(OP)are common diseases in middle-aged and elderly people,and the number of patients with both diseases has gradually increased in recent years.Because the onset of the disease is hidden,it is easy to cause fractures and serious complications of heart,brain and kidney in the later stage,which not only seriously damages the quality of life of patients,but also increases the difficulty of clinical treatment.Therefore,it is particularly necessary to strengthen the research on this disease.More and more studies have found that the disorder of intestinal flora will lead to the occurrence of OP,while the intestinal flora of patients with hypertension is obviously out of balance.Therefore,this paper thinks that intestinal flora may be the key influencing factor of hypertension complicated with OP,and the imbalance of intestinal flora will lead to the imbalance of short-chain fatty acid metabolism,immune inflammatory reaction and increased sympathetic nerve activity,thus causing the imbalance of bone homeostasis and promoting the occurrence of OP.Therefore,it is suggested that regulating intestinal flora may be a new way to intervene hypertension complicated with OP.

Objective To observe the effects of Zhengan Xifeng decoction on bile acid spectrum of bile and sterol 12α hydroxylase(CYP8B1)in spontaneously hypertensive rats(SHR).Methods Fifty SHR were randomly divided into model group,control group(1.0 mg·kg-1·d-1 benazepril by gavage)and experimental-L,-M,-H groups(8.63,17.25 and 34.50 g·kg-1·d-1 Zhengan Xifeng decoction by gavage),another 10 homologous male Wistar-Kyoto(WKY)rats were taken as the normal group.The model group and the normal group were given the same amount of distilled water.The rats in the 6 groups were administered once a day for 8 weeks.The animal non-invasive sphygmomanometer was used to measure the blood pressure of rats in each group by tail-cuff method;the bile acid spectrum of rats in each group was detected by UPLC-MS/MS;the expression of CYP8B1 mRNA in rat liver tissue was detected by real-time fluorescence quantitative polymerase chain reaction.Results The systolic blood pressure at the 8th week of the experimental-M,-H groups,control group,model group,normal group were(169.63±12.10),(170.32±9.64),(175.95±15.47),(189.47±7.42)and(146.40±9.45)mmHg;the diastolic blood pressure at the 8th week were(135.10±11.99),(129.73±15.10),(135.18±17.62),(149.20±8.83)and(110.53±10.92)mmHg;the relative expression levels of CYP8B1 mRNA were 3.36±0.94,5.45±1.46,4.29±0.95,0.89±0.14 and 1.00±0.00,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups were statistically significant(P＜0.01,P＜0.05).Compared with the model group,the bile acid spectrum of experimental-L,-M,-H groups bile changed significantly,and a total of 9 different bile acids were found,which were hyodeoxycholic acid,glycohyodeoxycholic acid,glycochenodeoxycholic acid,glycoursodeoxycholic acid,α-muricholic acid,ursodeoxycholic acid,cholic acid,β-muricholic acid and glycocholic acid.Conclusion Zhengan Xifeng decoction may correct bile acid spectrum disorder of bile and reduce blood pressure by up-regulating liver CYP8B1 expression.

Objective:To compare the long-term prognosis between open versus closed reduction and internal fixation in the treatment of unstable pelvic fractures.Methods:The data of 402 consecutive patients with unstable pelvic fracture were retrospectively analyzed who had been treated at The First Medical Center and The Fourth Medical Center, PLA General Hospital, and Strategic Support Force Specialty Medical Center from March 2011 to March 2017. This cohort was divided into 2 groups according to the reduction methods. In the open group of 194 cases subjected to open reduction and internal fixation, there were 133 males and 61 females with a median age of 43.0 (30.7, 51.0) years, and 35 cases of type B and 159 cases of type C by the Tile classification. In the closed group of 208 cases subjected to closed reduction and internal fixation, there were 115 males and 93 females with a median age of 45.5 (32.0, 56.0) years, and 40 cases of type B and 168 cases of type C by the Tile classification. The 2 groups were compared in terms of 12-items Short Form Health Survey (SF-12) scores [physical component summary (PCS) and mental component summary (MCS)] at the last follow-up, time from injury to operation, frequency of intraoperative X-ray fluoroscopy, intraoperative and postoperative blood transfusion, operation time, and quality of postoperative fracture reduction.Results:There was no statistically significant difference between the 2 groups in the preoperative general data except for the gender, showing the 2 groups were comparable ( P>0.05). This cohort of 402 patients was followed up for 7.8(6.2, 8.8) years. At the last follow-up, the PCS [49.9 (45.4, 55.4) points] and MCS [53.1 (46.4, 57.6) points] in the closed group were significantly higher than those in the open group [48.2 (41.4, 52.7) and 46.5 (40.6, 53.6) points] ( P<0.05). The closed group incurred significantly shorter time from injury to operation [6 (5, 8) d] and operation time [180 (126, 260) min] than the open group [9 (6, 13) d and 240 (165, 334) min], significantly less intraoperative and postoperative blood transfusion [1.5 (0, 4.0) U] than the open group [5.0 (2.9, 8.0) U], significantly higher frequency of intraoperative X-ray fluoroscopy [104.5 (85.0, 132.0) times] than the open group [21.0 (18.0, 26.0) times], and a significantly higher excellent and good rate of postoperative fracture reduction (92.8%, 193/208) than the open group (86.6%, 168/194) (all P<0.05). Conclusion:In the treatment of patients with unstable pelvic fractures, compared with open reduction and internal fixation, closed reduction and internal fixation can not only significantly shorten the waiting time and operation time of patients, reduce the transfusion during operation, but also achieve better fracture reduction to ultimately improve the quality of life of patients.

OBJECTIVES: To explore the association between assisted reproductive technology (ART) and birth weight discordance in twins (BWDT). METHODS: A retrospective analysis was conducted on twin infants born between January 2011 and December 2020 at the Third Affiliated Hospital of Guangzhou Medical University, with complete basic birth data. The impact of ART on the occurrence of BWDT was identified by the multivariate logistic regression analysis. RESULTS: A total of 3 974 pairs of twins were included, with 1 431 conceived naturally and 2 543 through ART. Neonates in the ART group had higher birth weights than those in the naturally conceived group (P<0.001). The incidence of BWDT was lower in the ART group compared to the naturally conceived group (16.17% vs 21.09%, P<0.001). The multivariate logistic regression analysis, adjusting for confounding factors such as maternal age, parity, pre-pregnancy body mass index, gestational diabetes, hypothyroidism, gestational age, and chorionic properties, showed no significant difference in the risk of BWDT between the ART and naturally conceived groups (P>0.05). CONCLUSIONS ART is not associated with the risk of BWDT.
Pregnancy ; Infant, Newborn ; Female ; Humans ; Birth Weight ; Pregnancy Outcome ; Infant, Premature ; Infant, Low Birth Weight ; Pregnancy, Multiple ; Premature Birth/epidemiology* ; Retrospective Studies ; Population Surveillance ; Reproductive Techniques, Assisted/adverse effects* ; Pregnancy Complications

Objective To analyze the status and trend for the mortality and DALY rates of child growth failure (CGF) in children aged < 5 years in China from 1990 to 2019, so as to provide a scientific basis for CGF prevention and control. Methods The mortality and DALY rates of CGF in children aged < 5 years from 1990 to 2019 were obtained from GBD 2019. The changes of these indicators with the years in China , the United States, Japan, Russia, India and the global were compared and analyzed. Results In 2019, the mortality of child wasting, child stunting and child underweight in children aged < 5 years in China were 9.62/100 000, 1.23/100 000, and 1.29/100 000 respectively, the mortality rates were 867.50/100 000 , 129.23/100 000 , and 112.87/100 000 rescpectively, higher than those of the United States, Japan, and Russia, and far lower than those of India and the global. The disease burden of three types of CGF were all higher in males than females, and higher in children aged < 1 years than children aged 1-4 years. From 1990 to 2019, the mortality and DALY rates of CGF in children aged < 5 years in China decreased from 300.41/100 000 and 26 445.38/100 000 to 10.49/100 000 and 943.57/100 000, respectively. China had the largest drop rate compared with all analyzed countries. As for children aged < 5 years in China, the DALY rate of lower respiratory infection ranked first in all the diseases caused by CGF. Conclusion From 1990 to 2019, the disease burden of CGF in children aged < 5 years has shown a significant decrease in China , but it is still far behind the developed countries. In the future, more attention should be paid to the problems of child growth in hope of reducing the mortality and DALY rates of CGF.

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: To analyze the safety of an inactivated 2019-nCoV vaccine (Vero cell) in adults aged 60 years and older. Methods: A randomized, double-blind, placebo-controlled clinical study was conducted in May 2020 The eligible residents aged 60 and above were recruited in Renqiu city, Hebei Province. A total of 422 subjects (phase Ⅰ/Ⅱ:72/350) were enrolled. Two doses of the trial vaccine or placebo were randomly administered according to a 0 and 28-day immunization schedule. Subjects were randomly divided into two groups in Phase Ⅰ. Within each group, participants received vaccine or placebo in a ratio of 2∶1. Subjects were randomly divided into four groups in phase Ⅱ to receive low-dose, medium-dose, high-dose vaccine and placebo, respectively, in a ratio of 2∶2∶2∶1. A combination of regular follow-up and active reporting was used to observe adverse reactions within 28 days after vaccination, and compare the incidence rate of adverse reactions in the trial and control groups. Results: 422 subjects were (66.45±4.70) years old, and 48.82% were male (206/422). There were 100, 124, 124 and 74 patients enrolled into the low-dose, medium-dose, high-dose vaccine groups and the placebo group, respectively. One person without the vaccination was removed, and 421 participants who received at least one dose of vaccine were included in the safety analysis. Within 28 days after the first or second dose, a total of 20.67% (87/421) subjects had adverse reactions (both solicitation and non-solicitation). About 76 patients suffered grade 1 adverse reactions [18.05% (76/421)] and 22 patients suffered grade 2 adverse reactions [5.23% (22/421)]. No grade 3 or above adverse reactions occurred. A total of 19.71% (83/421) subjects had solicited adverse reactions. The most common grade 1 adverse reaction was injection site pain, followed by fever and fatigue. The most common grade 2 adverse reactions were fever and fatigue, followed by muscle pain and injection site redness. A total of 2.61% (11/421) subjects had unsolicited adverse reactions. A total of 1.66% (7/421) subjects had serious adverse events after vaccination, and no serious vaccine-related adverse events were reported. Conclusions: The inactivated SARS-CoV-2 vaccine is safe for people aged 60 years and above.
Adult ; Aged ; Antibodies, Viral ; COVID-19/prevention & control* ; COVID-19 Vaccines ; Fatigue ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; Vaccination

Objective: To investigate the occurrence of live-born twins with birth weight-discordance and its relationship to adverse birth outcomes. Methods: A retrospective analysis was performed on 4 011 pairs of live-born twins in the Third Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2020. Based on the birth-weight discordance (∆BW, ∆BW=(birth-weight_big-birth-weight_small)/birth-weight_big×100%)), twins were divided into 4 groups, including ∆BW≤15%,>15%-20%,>20%-25%, and>25%. The differences in maternal and neonatal outcomes among 4 groups were explored. Then the correlation between ∆BW and neonatal adverse outcomes were explored. Results: The ΔBW was 9 (4, 16)% and males were accounted for 53.8% (4 315 cases) of 4 011 pairs of twins. The gestational age was (35.3±2.7) weeks at birth. There were 2 908 pairs (72.5%) of twins with ΔBW≤15%, 481 pairs (12.0%) with ΔBW>15%-20%, 281 pairs (7.0%) with ΔBW 20%-≤25%, and 341 twin pairs (8.5%) with ΔBW>25%. With ∆BW of 20% as the diagnostic cutoff, the incidence of birth weight discordance was 15.5% (622/4 011). The proportion of natural births in the ∆BW≤15% group was higher than that in the ∆BW>15%-20% group (10.5% (288/2 740) vs. 6.3% (29/463), P<0.008 3). The ∆BW>25% group had a significantly higher prevalence of maternal hypertensive disorders during pregnancy than that of the other 3 groups (25.5% (87/341) vs. 16.7% (47/281) vs.17.3% (83/480) vs. 13.8% (400/2 899), all P<0.008 3). Univariate analysis found that the ΔBW>25% group had a lower gestational age and a higher rate of preterm birth than the other groups. The rate of extremely low birth weight (ELBW) or very low birth weight (VLBW), small for gestational age (SGA), and transferring to the department of neonatology in the smaller twins were significantly different among the 4 groups (all P<0.05). Multivariate analysis showed that higher degree of birth weight discordance was all positively associated with the rate of ELBW, SGA, and transferring to the department of neonatology in smaller twin, even after adjusting maternal age and gestational hypertension, year of birth, mode of delivery, gender, and gestational age (all P<0.05). Moreover, the Mantel-Haenszel test also indicated that there were significantly low to moderate correlations between ΔBW and the unfavorable outcomes (r=0.22, 0.53, 0.21, all P<0.001, respectively). The receiver operating characteristic (ROC) curve found that adverse birth outcomes would be well predicted by birth weight-discordant when the diagnostic cut-off of ΔBW was 12%-17%, with an acceptable sensitivity (0.53-0.78) and a high specificity (0.72-0.79). Conclusions: Birth weight discordant is not uncommon in live-born twins, and is associated with adverse outcomes including ELBW, SGA, and transferring to the department of neonatology in the small twins. Besides, the risk is linearly related to the increase of ΔBW. In the future, more researches are needed to explore the underline mechanism and long-term impact of birth weight discordance, to guide the prevention and management.
Birth Weight ; Female ; Fetal Growth Retardation ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Male ; Pregnancy ; Premature Birth/epidemiology* ; Retrospective Studies ; Twins