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.

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 whether butorphanol tartrate as an adjuvant of ropivacaine for brachial plexus block can reduce the incidence of rebound pain after brachial plexus block.Methods Based on sample size calculation,174 patients undergoing upper limb bone surgery were included in this study and randomized into three groups using statistical software:butorphanol tartrate compound local anesthetic(group B1),brachial plexus block with 0.25%ropivacaine 20 mL(including adjuvant butorphanol 1mg);intravenous butorphanol group(group B2),brachial plexus block with 0.25%ropivacaine 20 mL,in addition,1mg of butorphanol was administered i.v;control(group C),only 0.25%ropivacaine 20ml for brachial plexus block.The patients were visited the day before operation,and the basic information of the patients was obtained.At the same time,the Douleur Neuropathique 4 questions(DN4)was used to evaluate whether there were neuropathic components(DN4≥4)in the site to be operated on,and the Numerical rating scale(NRS)was introduced to the patients,and the preoperative NRS value was obtained.30 minutes before the operation,the same anesthesiologist with rich experience in nerve block completed the ultrasound-guided brachial plexus block(interscalene approach),and tested whether the block effect was perfect.After entering the operating room,the patients were given general anesthesia,and the duration of operation,vital signs during operation,dosage of analgesics and whether or not using tourniquet were recorded.After the operation,the patients were sent to the postanesthesia care unit,and then sent to the ward when the patients reached the standard of leaving the room.Distribute pain diaries to patients and their families and instruct them to fill in relevant matters.The patients were followed up at 0 h,6 h,12 h,18 h,24 h and 36 h after operation to obtain the NRS value at each time point after operation,the time when the block disappeared and the highest NRS value within 12 hours,the first use of rescue analgesics,the use of postoperative analgesics,postoperative adverse events and the quality of patient recovery.Results The incidence of rebound pain was 31.6%in B1,48.2%in B2,and 54.4%in C.The pairwise comparison showed statistical difference between B1 and C(P<0.05).Rebound pain score in the three groups was B1 group0.05).There were no statistical differences in the duration of motor block,sensory block duration,duration of analgesia,time to first request for rescue analgesia,and QoR-15 recovery quality score(P>0.05).There was no statistical difference in the incidence of postoperative adverse effects among the three groups(P>0.05).Conclusion This study found that brachial plexus block with 1mg butorphanol tartrate as an adjuvant for ropivacaine reduced the incidence of rebound pain and rebound pain scores after upper limb orthopedic surgery and reduced postoperative opioid consumption.

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.

Objective This study applies Roy adaptation theory to deeply explore the experience of food avoid-ance behavior in patients with inflammatory bowel disease(IBD),offering insights for developing dietary management strategies.Methods A descriptive qualitative research method was employed.By purposive sampling,24 IBD pa-tients hospitalized in the gastroenterology department of a tertiary hospital in Nanjing from July 2022 to December 2024 were selected for semi-structured interviews.Data were analyzed using a directed content analysis approach.Results This study identified 4 main themes and 11 sub-themes,encompassing overattribution leading to inappro-priate avoidance(recurrent symptoms triggering overattribution,disease staging triggering inappropriate avoidance),negative self-perception leading management struggles(illness fear diminishing self-efficacy,disease trauma eroding self-identity,knowledge deficiency constraining self-determination),functional impairment intensifying role challenges(role internalization undermining social function,social roles relinquishing dietary management),and external con-straints amplifying practical difficulties(family and friend oversight heightening dietary stress,healthcare gaps foster-ing practical helplessness,traditional beliefs restricting dietary exploration,economic hardship limiting balanced nu-trition).Conclusion The interplay of overattribution,negative self-perception,functional impairment,and external constraints in IBD patients hinders their ability to adapt to disease fluctuations,ensnaring them in the adaptive predicament of food avoidance behavior.Healthcare professionals should comprehensively address these factors by fostering accurate perceptions,enhancing psychological support,guiding effective coping strategies,and optimizing ex-ternal resources,thereby improving patients' overall adaptive capacity and promoting their recovery.

Objective To explore whether butorphanol tartrate as an adjuvant of ropivacaine for brachial plexus block can reduce the incidence of rebound pain after brachial plexus block.Methods Based on sample size calculation,174 patients undergoing upper limb bone surgery were included in this study and randomized into three groups using statistical software:butorphanol tartrate compound local anesthetic(group B1),brachial plexus block with 0.25%ropivacaine 20 mL(including adjuvant butorphanol 1mg);intravenous butorphanol group(group B2),brachial plexus block with 0.25%ropivacaine 20 mL,in addition,1mg of butorphanol was administered i.v;control(group C),only 0.25%ropivacaine 20ml for brachial plexus block.The patients were visited the day before operation,and the basic information of the patients was obtained.At the same time,the Douleur Neuropathique 4 questions(DN4)was used to evaluate whether there were neuropathic components(DN4≥4)in the site to be operated on,and the Numerical rating scale(NRS)was introduced to the patients,and the preoperative NRS value was obtained.30 minutes before the operation,the same anesthesiologist with rich experience in nerve block completed the ultrasound-guided brachial plexus block(interscalene approach),and tested whether the block effect was perfect.After entering the operating room,the patients were given general anesthesia,and the duration of operation,vital signs during operation,dosage of analgesics and whether or not using tourniquet were recorded.After the operation,the patients were sent to the postanesthesia care unit,and then sent to the ward when the patients reached the standard of leaving the room.Distribute pain diaries to patients and their families and instruct them to fill in relevant matters.The patients were followed up at 0 h,6 h,12 h,18 h,24 h and 36 h after operation to obtain the NRS value at each time point after operation,the time when the block disappeared and the highest NRS value within 12 hours,the first use of rescue analgesics,the use of postoperative analgesics,postoperative adverse events and the quality of patient recovery.Results The incidence of rebound pain was 31.6%in B1,48.2%in B2,and 54.4%in C.The pairwise comparison showed statistical difference between B1 and C(P<0.05).Rebound pain score in the three groups was B1 group0.05).There were no statistical differences in the duration of motor block,sensory block duration,duration of analgesia,time to first request for rescue analgesia,and QoR-15 recovery quality score(P>0.05).There was no statistical difference in the incidence of postoperative adverse effects among the three groups(P>0.05).Conclusion This study found that brachial plexus block with 1mg butorphanol tartrate as an adjuvant for ropivacaine reduced the incidence of rebound pain and rebound pain scores after upper limb orthopedic surgery and reduced postoperative opioid consumption.

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.

Objective This study applies Roy adaptation theory to deeply explore the experience of food avoid-ance behavior in patients with inflammatory bowel disease(IBD),offering insights for developing dietary management strategies.Methods A descriptive qualitative research method was employed.By purposive sampling,24 IBD pa-tients hospitalized in the gastroenterology department of a tertiary hospital in Nanjing from July 2022 to December 2024 were selected for semi-structured interviews.Data were analyzed using a directed content analysis approach.Results This study identified 4 main themes and 11 sub-themes,encompassing overattribution leading to inappro-priate avoidance(recurrent symptoms triggering overattribution,disease staging triggering inappropriate avoidance),negative self-perception leading management struggles(illness fear diminishing self-efficacy,disease trauma eroding self-identity,knowledge deficiency constraining self-determination),functional impairment intensifying role challenges(role internalization undermining social function,social roles relinquishing dietary management),and external con-straints amplifying practical difficulties(family and friend oversight heightening dietary stress,healthcare gaps foster-ing practical helplessness,traditional beliefs restricting dietary exploration,economic hardship limiting balanced nu-trition).Conclusion The interplay of overattribution,negative self-perception,functional impairment,and external constraints in IBD patients hinders their ability to adapt to disease fluctuations,ensnaring them in the adaptive predicament of food avoidance behavior.Healthcare professionals should comprehensively address these factors by fostering accurate perceptions,enhancing psychological support,guiding effective coping strategies,and optimizing ex-ternal resources,thereby improving patients' overall adaptive capacity and promoting their recovery.