Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

Objective:To analyze the effectiveness and interobserver agreement of the Parer five-tier, the National Institute of Child Health and Human Development (NICHD) three-tier, and the International Federation of Gynecology and Obstetrics (FIGO) three-tier electronic fetal monitoring (EFM) systems in identification of neonatal acidosis during labor.Methods:This retrospective study was conducted on full-term singleton cephalic deliveries with neonatal acidosis (umbilical artery blood gas pH≤7.1) and normal newborns (umbilical artery blood gas pH≥7.2) in the Nanjing Drum Tower Hospital, Nanjing University Medical School from January to December 2020. EFM tracings during the last 30-60 min before delivery were collected. Four obstetricians independently described the features of randomly sorted and coded EFM tracings. Another obstetrician categorized these tracings using the NICHD three-tier, FIGO three-tier, and Parer five-tier evaluation systems based on the features. All researchers were masked to the clinical characteristics and maternal and neonatal outcomes. The sensitivity and specificity for identifying neonatal acidosis, as well as the interobserver agreement, were analyzed for all three systems. Independent sample t-test, Chi-square (or Fisher's exact test) and Mann-Whitney U tests were used for statistical analysis. Inter-group comparisons of sensitivity and specificity between the three evaluation systems were assessed using McNemar's test. The Kappa statistic was used to analyze interobserver agreement. Results:This study included a total of 3 558 cases. After propensity score matching, there were 44 cases of neonatal acidosis and 78 control cases. There were no significant differences in parity, gestational weeks, modes of delivery, placental abruption, or analgesia rates between the two groups. The rates of instrumental vaginal delivery and neonatal intensive care unit (NICU) admission in the acidosis group were significantly higher than those in the control group [15.8% (7/44) vs. 2.6% (2/78), χ2=8.45, P=0.003; 31.8% (14/44) vs. 12.8% (10/78), χ2=8.45, P=0.004], while the umbilical artery blood pH and mean base excess were lower in the acidosis group than in the control group [7.04±0.07 vs. 7.30±0.05, t=4.98; (－12.40±3.32) vs. (－5.64±1.95) mmol/L, t=13.61; both P<0.001]. (2) Using the NICHD three-tier system, 95.5% (42/44) of the acidosis cases and 89.7% (70/78) of the control cases were classified as having category Ⅱ EFM tracings, indicating potential fetal acid-base imbalance; category Ⅲ EFM tracings were only observed in 4.5% (2/44) of the cases in the acidosis group. With the FIGO three-tier system, 81.8% (36/44) of the acidosis cases were categorized as having "pathological" tracings, and with the Parer five-tier system, 86.4% (38/44) of the acidosis cases were correctly classified into the "orange or red" risk zones that indicated acid-base imbalance. Among the control cases, there were 28.2% (22/78) with EFM tracings of "normal patterns" categorized by the FIGO three-tier system, and 41.0% (32/78) classified into the "green or blue" risk zones by the Parer five-tier system, which indicated good fetal conditions. None of the acidosis cases were misdiagnosed as being normal by the Parer five-tier system. (3) Compared with the NICHD three-tier system, both the FIGO three-tier and the Parer five-tier systems showed increased diagnostic sensitivity [4.5% (1.2%- 14.5%) vs. 81.8% (66.8%-89.4%) and 86.4% (71.8%-92.4%)], but decreased specificity [100.0% (95.3%- 100.0%) vs. 87.2% (78.0%-92.9%) and 84.6% (75.0%-91.0%)]. There was no statistically significant difference in the sensitivity or specificity between the FIGO three-tier and Parer five-tier systems for identifying neonatal acidosis ( P=0.727 and 0.791). (4) When reading the tracings of control cases, the total agreement rate for the NICHD three-tier system by different observers was as high as 94.2%, while the total agreement rates for the FIGO three-tier and Parer five-tier systems were 69.7% and 67.7%, respectively. In the interpretation of EFHR tracings for acidosis cases, the interobserver agreement for the Parer five-tier system was excellent [Kappa (95% CI): 0.87 (0.79-0.95)], while both the NICHD three-tier and FIGO three-tier systems showed good agreement [Kappa (95% CI): 0.77 (0.66-0.88) and 0.72 (0.60-0.84)]. Conclusions:The Parer five-tier and the FIGO three-tier systems have higher sensitivity in identifying neonatal acidosis than the NICHD three-tier system, and the Parer five-tier system achieves a higher negative predictive value and a greater agreement in the interpretation of pathological EFM patterns.

The management of surplus drugs is an important part of drug administration. At present, China′s medical institutions are in the initial exploration stage in managing surplus drugs.This study analyzed the causes, safety hazards, management policies, and management problems of surplus drugs in medical institutions, and proposed targeted countermeasures and suggestions, including establishing unified and standardized management methods, consensus or guidelines, optimizing internal management of medical institutions, improving the management awareness of medical staff, and clarifying the benefits of surplus drugs, so as to provide references for medical institutions to manage surplus drugs reasonably.

To standardize the management of surplus drugs, improve the efficiency of medical resource utilization, promote the rational use of medical insurance funds, and reduce the financial burden on patients, a large tertiary hospital implemented a practice for managing surplus drugs starting in May 2023. This practice encompassed multiple aspects, including the establishment of organizational structure, clarification of responsibilities, formulation of billing for fractional doses and a reasonable surplus drugs list, establishment of standardized management processes, and allocation of special funds for surplus drugs. These efforts had initially achieved effective management of surplus drugs. As of November 2023, the management of surplus drugs had benefited 136 908 patients, with an average savings of 873.61 yuan per patient and a cumulative savings of approximately 34.7 million yuan in medical insurance funds. This practice had effectively reduced the wastage of medical resources, and could provide references for promoting standardized management of surplus drugs in medical institutions of China. In the future, the hospital should further expand the coverage of surplus drugs, ensure patients′ rights to informed consent, and establish a comprehensive performance incentive mechanism to promote the sustainable development of surplus drug management.

Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.
Humans ; Male ; Mice ; Rats ; Animals ; Caspase 3/metabolism* ; Mice, Nude ; Cell Line, Tumor ; Rats, Sprague-Dawley ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Prostatic Neoplasms/pathology* ; Cell Proliferation ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Mammals/metabolism*

Objective: To analyze the phenotypic-genotypic characteristics of hereditary deafness caused by OTOA gene variations. Methods: Family histories, clinical phenotypes and gene variations of six pedigrees were analyzed, which were diagnosed with hearing loss caused by OTOA gene variations at the PLA General Hospital from September 2015 to January 2022. The sequence variations were verified by Sanger sequencing and the copy number variations were validated by multiplex ligation-dependent probe amplification (MLPA) in the family members. Results: The hearing loss phenotype caused by OTOA variations ranged from mild to moderate in the low frequencies, and from moderate to severe in the high frequencies in the probands, which came from six sporadic pedigrees, among which a proband was diagnosed as congenital deafness and five were diagnosed as postlingual deafness. One proband carried homozygous variations and five probands carried compound heterozygous variations in OTOA gene. Nine pathogenic variations (six copy number variations, two deletion variations and one missense variation) and two variations with uncertain significance in OTOA were identified in total, including six copy number variations and five single nucleotide variants, and three of the five single nucleotide variants were firstly reported [c.1265G>T(p.Gly422Val),c.1534delG(p.Ala513Leufs*11) and c.3292C>T(p.Gln1098fs*)]. Conclusions: OTOA gene variations can lead to autosomal recessive nonsyndromic hearing loss. In this study, the hearing loss caused by OTOA defects mostly presents as bilateral, symmetrical, and postlingual, and that of a few presents as congenital. The pathogenic variations of OTOA gene are mainly copy number variations followed by deletion variations and missense variations.
Humans ; DNA Copy Number Variations ; Hearing Loss, Sensorineural/genetics* ; Deafness/genetics* ; Hearing Loss/genetics* ; Phenotype ; Genotype ; Nucleotides ; Pedigree ; Mutation ; GPI-Linked Proteins/genetics*

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Objective Calculus Bovis(CB)is a kind of valuable traditional Chinese medicine,which has been used in clinic for a long time.It has been shown to have significant anti-stroke,anti-inflammatory and anti-tumor effects.But its mechanism for treating Prostate cancer(PCa)remains unclear.The purpose of this study was to explore the target and mechanism of its action in the treatment of prostate cancer throμgh network pharmacology and in vitro and in vivo experiments.Methods The effective compounds of Calculus Bovis were collected by TCM pharmacology database and analysis platform(TCMSP).Search for potential compound targets in TCMSP.Search the Drμgbank,GeneCards,OMIM,PharmGkb,and TTD databases for disease targets associated with prost cancer.Disease and compound targets were integrated in the STRING database to construct their interaction network(PPI)to reveal the key targets of compound treatment for prostate cancer.In order to elucidate the mechanism of Calculus Bovis in the treatment of prostate cancer,GO functional enrichment and KEGG pathway enrichment analysis were conducted using Cytoscape software.The mechanism of treating prostate cancer with Calculus Bovis was studied in vitro and in vivo.Results A total of 11 compounds with anti-prostate cancer activity were identified.Oleanolic acid,ursolic acid,ergosterol,deoxycorticosterone,methylcholine and cholverdin were potential effective components.A total of 367 targets of Calculus Bovis compounds and 2152 targets of prostate cancer were found.The core targets of Calculus Bovis in the treatment of prostate cancer included TP53,STAT3,AKT1,HSP90AA1,ESR1,SRC,JUN,RELA,CCND1,CDKN1A,EGFR,AR,etc.The biological functions of Calculus Bovis mainly involve oxidative stress response,response to steroid hormones,cell response to chemical stress,peptide-serine modification and phosphorylation,and protein serine/threonine kinase activity.Calculus Bovis treatment of prostate cancer mainly involves PI3K-AKT signaling pathway,TNF signaling pathway,MAPK signaling pathway,etc.In vitro and in vivo experiments showed that Calculus Bovis promoted apoptosis of PC3 cells of prostate cancer by inhibiting PI3K-AKT signaling pathway.Conclusion Calculus Bovis has a therapeutic effect on prostate cancer,and its function is related to inhibiting PI3K-AKT signaling pathway and promoting apoptosis of cancer cells.

ObjectiveTo establish a simple， fast and accurate method for locating the volatile oil in Angelicae Sinensis Radix based on frozen section and fluorescence imaging technology， and to reveal the distribution and accumulation of volatile oil in the roots of this herbal medicine. MethodAngelicae Sinensis Radix was used as the research material， the best frozen section conditions for the research material were established by comparing the effects of different cryoprotectants on the quality of frozen sections of Angelicae Sinensis Radix. The suitability of Sudan Ⅲ chemical staining and fluorescence localization for positioning the volatile oil were compared according to the loss of volatile oil and the complexity of operation process. ResultA new method for evaluating the quality of frozen sections of Angelicae Sinensis Radix was established. According to the evaluation equation， it was found that the highest score was obtained when the head， body and tail positions of Angelicae Sinensis Radix were treated with 20% glycerol， 15% glycerol and 20% sucrose， respectively. There was yellowish-brown oily substance in the oil chambers of phelloderm and secondary phloem， and oil canal of the secondary xylem of Angelicae Sinensis Radix， which could be stained orange red or orange yellow by Sudan Ⅲ， and there was green spontaneous fluorescence in the same part under the fluorescence microscope. ConclusionThe relatively complete section of Angelicae Sinensis Radix can be obtained after being treated with cryoprotectant. The volatile oil exists in the oil chambers of phelloderm and secondary phloem， and oil canal of the secondary xylem of Angelicae Sinensis Radix. This study can provide reference for observation of the accumulation sites of volatile oil in other plants.

ObjectiveTo determine the chemical constituents of burdock （Arctium lappa） leaves， and elucidate dynamic accumulation rule of four main components， in order to provide the basis for determining the suitable harvest time of burdock leaves. MethodSilica gel， macroporous resin， Sephadex LH-20， octadecylsilane chemically bonded silica （ODS）， microporous resin （MCI） column chromatography and reversed-phase preparative high performance liquid chromatography （HPLC） were used to isolate the main chemical constituents in burdock leaves. Their chemical structures were elucidated by spectroscopic techniques. HPLC-diode array detector （DAD） was used to analyze the dynamic accumulation of four components in burdock leaf. HPLC-DAD was performed on a Shim-pack GIST C₁₈ column （4.6 mm×250 mm， 5 μm） with mobile phase of acetonitrile （A）-0.3% phosphoric acid aqueous solution （B） （0-9 min， 13%A； 9-10 min， 13%-24%A； 10-30 min， 24%A）， flow rate of 1.0 mL·min^-1， column temperature of 40 ℃， and detection wavelength at 328 nm. ResultSeventeen compounds were isolated from burdock leaves， and identified as caffeic acid （1）， rutin （2）， kaempferol-3-O-rutinoside （3）， quercetin-3-O-β-D-glucopyranoside （4）， kaempferol-3-O-β-D-glucopyranoside （5）， chlorogenic acid （6）， isochlorogenic acid A （7）， daucosterol （8）， ursolic acid （9）， anemarrhenoside B （10）， （-）-secoisolariciresinol （11）， vladinol D （12）， melitensin （13）， esculetin （14）， 1-（-2-ethylphenyl）-1，2-ethanediol （15）， 1-（-4-ethylphenyl）-1，2-ethanediol （16）， 3-hydroxy-1-（4-hydroxy-3，5-dimethoxyphenyl）-1-propanone （17）. The contents of chlorogenic acid， rutin and kaempferol-3-O-rutinoside in burdock leaves showed an upward trend from April to August， and reached the highest in August. And the content of isochlorogenic acid A firstly increased and then decreased from April to August， and reached the highest in July. ConclusionCompounds 10， 12-17 were isolated from Arctium for the first time. Taking the contents of chlorogenic acid， rutin， kaempferol-3-O-rutinoside， and isochlorogenic acid A as indicators， considering the comprehensive development and utilization of burdock roots and leaves， it is recommended to harvest burdock leaves in mid-August.