ObjectiveTo reveal the molecular mechanism by which the traditional Chinese medicine compound prescription Qiangjing tablets regulate the aging of the testicular tissue and Leydig cells in rats through the cyclin-dependent kinase 4 （CDK4）-early 2 factor （E2F） signaling pathway. MethodsFor the cell experiment， 2-month-old SPF-grade SD male rats were selected and randomly assigned into a blank control group （administrated with an equal volume of 0.9% sodium chloride injection） and a Qiangjing tablets group （20 rats in each group） according to body weight. The Leydig cell model of aging was established by treatment of TM3 cells with 100 μmol·L^-1 H₂O₂， and the modeling performance was evaluated based on the levels of p16 and p21 determined by Western blot. The antioxidant NAC （1 mmol·L^-1） was used as the positive control for eliminating reactive oxygen species （ROS）. Cells were intervened with Qiangjing tablets-containing serum at low （2.5%）， medium （5%）， and high （10%） concentrations. The testosterone level in the cell supernatant was determined by enzyme-linked immunosorbent assay （ELISA）， and the protein levels of CDK4， E2F1， and E2F2 were analyzed by Western blot. In the animal experiment， 19-month-old naturally aging rats were used as the model group， and 2-month-old rats as the young control group. The positive control group was subcutaneously injected with 5.21 mg·kg^-1·d^-1 testosterone propionate. Qiangjing tablets were administered by gavage at low， medium， and high doses of 0.72， 1.44， 2.88 g·kg^-1·d^-1， respectively. The general conditions of rats were observed， and the protein levels of CDK4， E2F1， and E2F2 in the testicular tissue were determined by Western blot. ResultsIn the cell experiment， compared with the blank control group， the model group showed upregulated expression of CDK4 and E2F1 （P<0.05） and slightly downregulated expression of E2F2. Compared with that in the model group， the expression of CDK4 was upregulated in the NAC group and the low-dose Qiangjing tablets group （P<0.05）， slightly upregulated in the medium-dose Qiangjing tablets group， and downregulated in the high-dose Qiangjing tablets group （P<0.05）. The NAC group showed downregulated expression of E2F1 （P<0.05） and E2F2， and the low-， medium-， and high-dose Qiangjing tablets groups showed downregulated expression of both E2F1 and E2F2 （P<0.05）. Compared with that in the NAC group， the expression of CDK4 was upregulated in the low-dose Qiangjing tablets group and downregulated in the medium-dose and high dose （P<0.05） groups. The expression of E2F1 was down-regulated in all the three dose groups， with statistically significance in the high dose group （P<0.05）， and that of E2F2 were downregulated in all the three dose groups （P<0.05）. In the animal experiment， compared with the young control group， the model group exhibited downregulated expression of CDK4 （P<0.05） and slightly upregulated expression of E2F1 and E2F2. Compared with that in the model group， the expression of CDK4 decreased in the testosterone propionate group and the low-dose Qiangjing tablets group （P<0.05） but increased in the medium-dose （P<0.05） and high-dose groups. In addition， the expression of E2F1 decreased （P<0.05）， and that of E2F2 was slightly elevated. Compared with that in the NAC group， CDK4 expression was elevated in the Qiangjing tablets groups， with statistical significance in the medium- and high-dose groups （P<0.05）. Similarly， the E2F1 expression was also upregulated in the Qiangjing tablets groups， with statistical significance in the medium-dose group （P<0.05）. The expression of E2F2 was downregulated in all the Qiangjing tablets groups. ConclusionQiangjing tablets delay the aging process of Leydig cells and testicular tissue by up-regulating the expression of CDK4 and lowering the levels of E2F1 and E2F2.

ObjectiveBased on the multidimensional correlation analysis framework of "disease， syndrome， formula， and medicine"， this study aims to systematically elucidate the regulatory effects of effective components in Qiangjing tablet on testosterone synthesis pathways in testicular Leydig cells under oxidative stress， providing a theoretical basis for the treatment of male infertility with traditional Chinese medicine and modern research on compounds. MethodsDisease targets for male infertility were obtained from The Human Gene Database （GeneCards， score ≥20）， the Comparative Toxicogenomics Database （CTD， score ≥150）， DrugBank （score ≥0.2）， and DisGeNET （score ≥0.2）. Targets related to the syndrome of kidney deficiency and blood stasis were acquired from the traditional Chinese medicine syndrome association database SymMap. Components of Qiangjing tablet were retrieved based on The Encyclopedia of Traditional Chinese Medicine （ETCM） database and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）， and they were screened according to a quantitative estimate of drug-likeness （QED ≥ 0.49） and a target confidence index>0.8. Intersecting targets were taken to construct a protein-protein interaction （PPI） network using the STRING database. The network was visualized with Cytoscape software and subjected to the functional annotation of gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis. Quality markers （Q-markers） were predicted via the ADMETlab 2.0 platform based on Lipinski's rule， Pfizer's rule， GSK's rule， and the Golden Triangle. For experimental validation， rats' testicular Leydig cells were used. Exosomes were extracted and loaded with active components via the ultrasonic method. Exosome concentration was determined using a BCA protein quantification kit. Morphology was observed using a transmission electron microscope. The particle size was analyzed with a particle size analyzer. The surface marker proteins such as cluster of differentiation 9 （CD9）， cluster of differentiation 63 （CD63）， and cluster of differentiation 81 （CD81） were identified by Western blot， and drug loading capacity was measured by high-performance liquid chromatography （HPLC）. An oxidative stress model was induced by alpha， alpha'-azodiisobutyramidine dihydrochloride （AAPH）， and Leydig cells were divided into the following groups： A control group， an AAPH group， a quercetin group （Que group）， an exosome group （Exo group）， and a QUE-loaded Exo group （Que-Exo group）. The cell viability was detected using the 3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide （MTT） thiazolyl blue assay. The reactive oxygen species （ROS） levels and mitochondrial membrane potential were measured by flow cytometry. The levels of oxidative indicators， including malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， catalase （CAT）， and testosterone （T）， were detected by enzyme-linked immunosorbent assay （ELISA）. The expressions of steroidogenic enzymes such as cytochrome p450 family 11 subfamily a member 1 （CYP11A1）， hydroxy-delta-5-steroid dehydrogenase， 3 beta- and steroid delta-isomerase 1 （HSD3B1）， and hydroxysteroid 17-beta dehydrogenase 3 （HSD17B3）， regulatory factors such as steroidogenic factor 1 （SF-1） and steroidogenic acute regulatory protein （StAR）， and miR-145-5p content， were detected by Western blot and real-time polymerse chain reaction （Real-time PCR）. ResultsNetwork pharmacology analysis reveals that the main active components of Qiangjing tablet for intervening in male infertility with kidney deficiency and blood stasis syndrome were Que， luteolin， etc.， with the core mechanism involving pathways such as steroid hormone biosynthesis. Experimental results show that compared with the control group， the AAPH group exhibits significantly reduced cell viability （P<0.01）， decreased mitochondrial membrane potential （P<0.01）， significantly elevated levels of ROS， MDA， and miR-145-5p （P<0.01）， significantly reduced activities of SOD， GSH-Px， and CAT， as well as reduced testosterone content （P<0.01）， and significantly downregulated protein and mRNA expressions of steroidogenic enzymes， SF-1， and StAR （P<0.01）. The above indicators were reversed in the Que and Que-Exo groups （P<0.05）. Compared with the Que group， the Que-Exo group showed more significant effects in enhancing cell viability， mitochondrial membrane potential， testosterone level， antioxidant enzyme activities， and expressions of key molecules in the steroidogenic pathway （P<0.05）. ConclusionThis study demonstrates that Que， an active component of Qiangjing tablet， inhibits oxidative stress reaction， improves mitochondrial function in Leydig cells， upregulates steroidogenic enzyme expression， and restores testosterone production. As a carrier for Que， Exo enhance its stability， delivery efficiency， and biological effect. Additionally， miR-145-5p may be closely associated with testosterone synthesis， though its precise molecular mechanism requires further exploration. By integrating traditional Chinese medicine compounds with modern scientific technology， this research expands the paths for the modernized research of traditional Chinese medicine and opens a novel therapeutic direction with translational potential for clinical intervention of male infertility.

Post-traumatic stress disorder (PTSD) is a relatively common but complex mental illness with a range of diverse risk factors. Typical symptoms include the re-experience or avoidance of traumatic events, cognitive impairment, and hypervigilance. While the exact pathogenesis of PTSD is unclear, many studies indicate that epigenetic regulation plays a key role in its development. Specifically, numerous studies have indicated that the levels of histone acetylation and methylation, DNA methylation, and noncoding RNA are altered in PTSD patients. Further to this, natural products have been found to achieve epigenetic regulation of PTSD by regulating the expression of epigenetic enzymes, long noncoding RNA (lncRNA), and miRNA, thereby playing a role in improving PTSD symptoms. To date, however, no epigenetic regulation related drugs have been used in the treatment of PTSD. Furthermore, while natural products that can epigenetically regulate PTSD have received increasing levels of attention, there have not yet been any systematic reports on the topic. Here, we summarized the roles and mechanisms of natural products in the epigenetic regulation of PTSD, providing a novel and unique perspective that will help to guide the development and application of new PTSD treatments.

OBJECTIVE To explore the changes of microribonucleic acid(miR)-223,miR-155 and miR-125 in the neonates with sepsis and analyze the distribution of pathogens so as to provide bases for clinical diagnosis and treatment of neonates with sepsis.METHODS A total of 39 neonates with sepsis who were treated in Jinan Second Maternal and Child Health Hospital from May 2021 to May 2023 were enrolled in the study and were assigned as the study group,meanwhile,42 healthy neonates who were born in the hospital were chosen as the control group.The distribution and drug resistance of the pathogens isolated from the neonates of the study group were statistically analyzed.The relative expression levels of peripheral blood miR-223,miR-155 and miR-125 were com-pared between the two groups,and the values of the three indexes in diagnosis of neonatal sepsis were analyzed.RESULTS Totally 46 strains of pathogens were isolated from the 39 neonates with sepsis,20 of which were Escherichia coli,and 10 were Staphylococcus aureus.The E.coli strains were resistant to ampicillin,tetra-cycline,ciprofloxacin and cefazolin;the S.aureus strains were resistant to penicillin,erythromycin,cefazolin and clindamycin,with the drug resistance rates higher than 50％.The expression level of miR-223 of the study group was 2.13±0.70,higher than that of the control group,the expression level of miR-125 of the study group was 0.92±0.30,higher than that of the control group;while the expression level of miR-155 of the study group was 2.08±0.68,lower than that of the control group(P＜0.05).The area under the curve(AUC)of the joint detec-tion of miR-223,miR-155 and miR-125 was 0.945 in diagnosis of neonatal sepsis,with the sensitivity 92.31％,the specificity 88.10％.CONCLUSIONS E.coli and S.aureus are dominant among the pathogens isolated from the neonates with sepsis.The neonates with sepsis show abnormal expressions of peripheral blood miR-223,miR-155 and miR-125,and the joint detection of the three indexes has high value in diagnosis of neonatal sepsis.

ObjectiveTo analyze the adverse reactions associated with the clinical use of Banxia （Rhizoma Pinelliae）- Wutou （Aconitum） in the same formula， with the aim of providing a reference for the safety of their clinical application. MethodsLiterature on the clinical application of antagonistic herbs "Banxia-Wutou" used in the same formula， published from January 1st， 2014， to June 30th， 2023， was retrieved from databases including CNKI， VIP， Wanfang， SinoMed， PubMed， Cochrane Library， and Embase. A database was established， and information related to adverse reactions was extracted， including descriptions， classifications， specific manifestations， management and outcomes， patients' primary diseases （western medicine diseases and traditional Chinese medicine diagnoses and syndromes）， and medication information （dosage， ratio， administration routes， and dosage forms）. ResultsA total of 79 researches simultaneously used antagonistic herbs Banxia-Wutou in the same formula and reported associated advers reactions. Gastrointestinal adverse reactions were the most common， with 8 studies reporting management of adverse reactions and 3 studies reporting improvement with no intervention. Among the 11 researches， the adverse reaction relieved to extant， while other 69 researches didn't report the managment of adverse reaction and its prognosis. For the primary disease in western medicine system， chronic bronchitis and chronic obstructive pulmonary disease （COPD） were most common， while gastric pain was the most common symptom in traditional Chinese medicine with spleen and kidney deficiency and spleen stomach cold deficiency being the most frequent syndromes. The most common Banxia dosage was 10 g， while for the Wutou， Fuzi （Radix Aconiti Lateralis Praeparata） was predominant with the highest dose at 15 g. The most frequent herbal combination was Banxia-fuzi， with a 1∶1 ratio. The main administration route was oral， and the primary dosage form was decoction. ConclusionGastrointestinal adverse reactions are the most common in the clinical use of Banxia-Wutou antagonistic herb combinations. Research on the safety of "Banxia-Wutou" combinations should focus on respiratory system diseases and spleen-stomach related conditions.

OBJECTIVE To explore the changes of microribonucleic acid(miR)-223,miR-155 and miR-125 in the neonates with sepsis and analyze the distribution of pathogens so as to provide bases for clinical diagnosis and treatment of neonates with sepsis.METHODS A total of 39 neonates with sepsis who were treated in Jinan Second Maternal and Child Health Hospital from May 2021 to May 2023 were enrolled in the study and were assigned as the study group,meanwhile,42 healthy neonates who were born in the hospital were chosen as the control group.The distribution and drug resistance of the pathogens isolated from the neonates of the study group were statistically analyzed.The relative expression levels of peripheral blood miR-223,miR-155 and miR-125 were com-pared between the two groups,and the values of the three indexes in diagnosis of neonatal sepsis were analyzed.RESULTS Totally 46 strains of pathogens were isolated from the 39 neonates with sepsis,20 of which were Escherichia coli,and 10 were Staphylococcus aureus.The E.coli strains were resistant to ampicillin,tetra-cycline,ciprofloxacin and cefazolin;the S.aureus strains were resistant to penicillin,erythromycin,cefazolin and clindamycin,with the drug resistance rates higher than 50％.The expression level of miR-223 of the study group was 2.13±0.70,higher than that of the control group,the expression level of miR-125 of the study group was 0.92±0.30,higher than that of the control group;while the expression level of miR-155 of the study group was 2.08±0.68,lower than that of the control group(P＜0.05).The area under the curve(AUC)of the joint detec-tion of miR-223,miR-155 and miR-125 was 0.945 in diagnosis of neonatal sepsis,with the sensitivity 92.31％,the specificity 88.10％.CONCLUSIONS E.coli and S.aureus are dominant among the pathogens isolated from the neonates with sepsis.The neonates with sepsis show abnormal expressions of peripheral blood miR-223,miR-155 and miR-125,and the joint detection of the three indexes has high value in diagnosis of neonatal sepsis.

ObjectiveTo compare the differences in intestinal absorption of nanophase（NP） formed by single decoction and combined decoction of Ginseng Radix et Rhizoma（GRR） and Zingiberis Rhizoma Recens（ZRR） in rats， and to investigate the effects of new NP formed by the combined decoction on the absorption of main components in GRR and ZRR. MethodDifferential centrifugation and dialysis techniques were used to enrich NP in the single and combined decoctions of GRR and ZRR， respectively. The microstructure， particle size， Zeta potential and concentration of the NP were analyzed by transmission electron microscope， particle size analyzer and nanoparticle tracking analyzer. Based on everted gut sac model， the index components in the intestinal absorption solution of NP from the single and combined decoctions were analyzed by ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）. The per unit area actual value of cumulative intestinal absorption（Q_actual）， absorption rate constant（K_a） and apparent permeability coefficient（P_app） were used as the evaluating indexes to investigate the absorption characteristics of the aforementioned NP in the duodenum， jejunum， ileum and colon. ResultIrregularly spherical NP was present in the single and combined decoctions， and the contents of components in NP of the combined decoction were mostly lower than those in the single decoction. In these NP， ten components could be absorbed into the intestinal sac， with the main absorption site being the small intestine， and the P_app was greater than 1×10^-5 cm·min^-1. Compared with NP in the single decoction， the Q_actual and K_a of ginsenoside Rb₁， ginsenoside Rf， 4-gingerol and 6-shogaol were significantly increased in NP of the combined decoction， while ginsenoside Re and 6-gingerol were significantly decreased（P<0.01）. Except for ginsenoside Re and ginsenoside Rd， the P_app of the remaining constituents was significantly increased in NP of the combined decoction（P<0.01）. In addition， the maximum intestinal segment site of Q_actual was shifted forward for ginsenoside Rb₁， ginsenoside Rd and ginsenoside Ro， while shifted backward for ginsenoside Rg₁， ginsenoside Re and 8-gingerol. The maximal intestinal segment sites of K_a and P_app of ginsenoside Rb₁， ginsenoside Rg₁， ginsenoside Rd and ginsenoside Ro shifted forward， while ginsenoside Re and 4-gingerol were shifted backward. ConclusionThe combined decoction of GRR and ZRR is helpful to promote the absorption of the effective components of the two， and changes the absorption behavior of the effective components in some intestinal segments. This study provides a reference for the subsequent research on the compatibility mechanism of the two medicines.

Objective:To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy.Methods:A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results:Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG ( χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG ( χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion:Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.

Objective To analyze the characteristics of conventional ultrasound and contrast-enhanced ultrasound(CEUS)in hypovascular renal tumors,and to explore the application value of combining the 2 methods in diagnosing benign and malignant hypovascular renal tumors.Methods The conventional ultrasound and CEUS data of 104 hypovascular renal tumors(76 benign lesions[benign group]and 28 malignant lesions[malignant group])from 99 patients,who were confirmed by postoperative pathology,biopsy pathology or computed tomography(CT)/magnetic resonance imaging(MRI)enhancement combined with long-term follow-up in Ruijin Hospital,Shanghai Jiao Tong University School of Medicine and its Wuxi Branch from Oct.13,2009 to Oct.26,2022,were retrospectively analyzed.The location,size,internal echo,morphology,internal and peripheral blood supply of the lesions were observed by conventional ultrasound,and the perfusion mode,regression pattern,perfusion uniformity and ring enhancement signs were observed by CEUS.Taking the pathological results or confirmed results of CT/MRI enhancement combined with long-term follow-up as the gold standard,the value of conventional ultrasound combined with CEUS in the differential diagnosis of benign and malignant hypovascular renal tumors was analyzed.Results There were significant differences in gender,age of patients and internal echo,contrast agent regression and ring enhancement signs of lesions between the 2 groups(all P＜0.05).The malignant tumors were mostly found in males(78.6％,22/28)with an average age of(58.29±11.76)years old;the masses were mostly hypoechoic(64.3％,18/28),and rapid washout was predominant with CEUS(60.7％,17/28).In the benign group,most of the patients were female(55.3％,42/76),with an average age of(50.64±14.88)years old;the majority of the masses were hyperechoic(64.5％,49/76),and CEUS showed simultaneous washout as the main lesion(56.6％,43/76).Three patients(10.7％,3/28)with ring enhancement signs were all malignant.The diagnostic accuracy(82.7％)and specificity(88.2％)for benign and malignant hypovascular renal tumors were relatively high when combining the diagnostic indicators of ring enhancement signs and hypoechoic.The diagnostic sensitivity(85.7％)and negative predictive value(92.3％)were relatively high when combining the 3 diagnostic indicators of ring enhancement,hypoechoic,and rapid washout.Conclusion Conventional ultrasound combined with CEUS has significant clinical practical value in the differential diagnosis of benign and malignant hypovascular renal tumors.The ring enhancement sign is highly specific in the diagnosis of malignant hypovascular renal tumors.However,if this sign is not significant and conventional ultrasound shows hypoechoic or CEUS exhibits rapid washout,there is a strong suggestion that the mass may be a malignant lesion.

Objective:To investigate the status quo of intravenous (IV) infusion device selection among hospitalized children and provide direction for improving practices related to the selection of infusion devices.Methods:A total of 1 306 hospitalized children undergoing IV infusion treatment in 11 clinical departments of Children's Hospital of Fudan University in June 2021 were selected by convenience sampling. A self-developed data collection form for the selection of IV infusion devices in hospitalized children and criteria for the appropriateness of IV infusion device selection were used to survey and evaluate the appropriateness of IV infusion device selection among these children.Results:IV infusion devices were found to have been appropriately selected in 1 137 of the 1 306 children, while these devices were inappropriately selected in 169 children. The inappropriate selection was primarily due to the improper choice of peripheral intravenous catheters (PIVC), with 155 cases involving the administration of non-peripheral compatible medications through PIVC. No significant statistical difference was found in the appropriateness of IV infusion device selection between the infant group and the child and adolescent group ( P>0.05). Significant differences were observed in the appropriateness of IV infusion device selection based on different physicochemical properties of medications and the duration of therapy ( P<0.01) . Conclusions:The standardization of IV infusion device selection among hospitalized children needs improvement. It is urgent to apply evidence from the Clinical Practice Evidence- Based Guidelines for Pediatric Intravenous Therapy regarding recommendations for IV infusion device selection, to initiate evidence application projects, and to standardize the selection of IV infusion devices.