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

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 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

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 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 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.

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

As a member of the dibenzyl isoquinoline alkaloid family, cepharathine is an alkaloid from the traditional Chinese medicine cepharathine, which is mainly used for treatment of leukopenia and other diseases. Recent studies of the inhibitory effect of cepharathine against SARS-CoV-2 have attracted widespread attention and aroused heated discussion. As the original discoverer of the anti-SARS-CoV-2 activity of cepharanthine, here we briefly summarize the discovery of cepharanthine and review important progress in relevant studies concerning the discovery and validation of anti-SARS-CoV-2 activity of cepharathine, its antiviral mechanisms and clinical trials of its applications in COVID-19 therapy.
Antiviral Agents/therapeutic use* ; Benzylisoquinolines/therapeutic use* ; COVID-19 ; Humans ; SARS-CoV-2

Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota.However,the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations.A well-controlled envi-ronment is thus necessary to reduce undesirable confounding effects,and recapitulate age-dependent changes in the gut microbiota of healthy primates.Herein we performed 16S rRNA gene sequenc-ing,characterized the age-associated gut microbial profiles from infant to elderly crab-eating maca-ques reared in captivity,and systemically revealed the lifelong dynamic changes of the primate gut microbiota.While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium,the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants,underlining their potential role in host development.Importantly,topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity,and its tremendous decline with age could probably be linked to healthy aging.Moreover,we identified key driver microbes responsible for such age-dependent network changes,which were further linked to altered metabolic functions of lipids,carbohydrates,and amino acids,as well as phenotypes in the microbial community.The current study thus demon-strates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota,and provides new insights into their roles in the development and healthy aging of their hosts.