Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

The theory of "brain-heart-kidney-semen chamber" axis is proposed based on the basic theories of traditional Chinese medicine， the modern physiological characteristics of men's diseases， and clinical practice. According to this theory， dysfunctions of the brain， heart， kidney， and semen chamber are the core mechanisms for the occurrence of premature ejaculation， and the loss of control of the opening and closing of the seminal orifices due to the dysfunction of the semen chamber is the final link in the occurrence of premature ejaculation. The treatment of premature ejaculation based on the theory of "brain-heart-kidney-essence chamber" axis highlights the overall regulation of the Zang-fu organs involved in the disease， while focusing on the simultaneous treatment of the mind and body. By exploring the biological basis of the "brain-heart-kidney-essence chamber" axis and premature ejaculation， we propose that the biological basis of premature ejaculation and the axis is mainly related to the function decline of the local brain area， neuromodulation malfunction， central neurotransmitter imbalance， endocrine disorders， and enhanced sensory afferents of the penis. This study aims at providing a new approach for the prevention and treatment of premature ejaculation by traditional Chinese medicine and a scientific basis for the development of more effective therapeutic methods.

Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

This article introduces an overview of management system for conflict of interest of the European Pharmacopoeia Commission (EPC) and the United States Pharmacopoeia Convention (USP). The EPC and USP have standardized the management system for conflict of interest in drug standard work in multiple management documents, such as the Guide for the Work, Code of Practice for the Work, Form for Declaration of Interests and Confidentiality Undertaking of the EPC, bylaws, Rules and Procedures of the Council of Experts, Code of Ethics, Standards of Conduct of the USP, in order to ensure the transparency and fairness of drug standard development, improve the credibility and rigor of drug standards. This article introduces the management system for conflict of interest of the EPC and USP, providing reference for the improvement of relevant management systems of the Chinese Pharmacopoeia Commission.

Male lower urinary tract symptoms is a collective term for a group of symptoms associated with lower urinary tract disorders characterized by frequent urination, urgent urination, and difficulty of urination, of which the common causes are benign prostatic hyperplasia or overactive bladder. With the aging of the global population, the incidence of male lower urinary tract symptoms is increasing year by year. Based on the theoretical connotation of " zang-fu extraordinary connection", the relationship between the lungs and the bladder, the spleen and the small intestine, and the kidneys and the sanjiao with the formation of male lower urinary tract symptoms is explained from three perspectives. It is believed that lung qi depression and closure, disturbance of qi transformation in bladder, and insufficient spleen transport occur, the small intestine is dysfunctional, kidney yang is exhausted, and obstruction of the sanjiao waterway are the basic pathogenesis of male lower urinary tract symptoms. It is emphasized that the location of the disease should be identified. If it is related to the lungs and the bladder, then the disease should be treated by lifting the pot to lift the lid and diffusing the lung qi to benefit the bladder with Wuling Powder plus perilla leaf and bitter apricot seed; if it is related to the spleen and the small intestines, then the disease should be treated by raising the clear and directing the turbid downward and improving the spleen qi in order to support the small intestines with Shenling Baizhu Powder; if it is related to the kidneys and the sanjiao, then the disease should be treated by seeking the yang within the yin and warming and tonifying the kidney qi in order to dredge up the sanjiao with Bawei Shenqi Pill. According to the patient's condition, treatment can be combined with acupuncture, exercise, and other therapies. This paper can provide reference for clinical treatment of male lower urinary tract symptoms.

Male infertility,a common condition in andrology,falls under the category of"no son"in traditional Chinese medicine(TCM).Unhealthy eating habits and excessive sexual activity,prevalent due to improved living standards,have contributed to the increasing incidence of male infertility.YE Tianshi proposed the theory of"maintaining with the sweet and restoring the body fluids",which emphasizes the importance of ample body fluid for the nourishment of the male essence chamber.Sufficient body fluid is crucial for normal sperm generation.In TCM,the primary pathogenesis of male infertility involves the loss of body fluids and insufficiency of yin essence.Sweet Chinese herbal medicinal is recommended as it nourishes yin,enriches essence,and replenishes male reproductive essence without producing phlegm and dampness.Therefore,when treating male infertility,attention should be given to the use of sweet Chinese herbal medicinal,adhering to the principle of"abundant body fluids nourish kidney yin,and abundant kidney yin supports semen production".Therapies such as purging fire to preserve body fluids with Zengye Decoction,nourishing yin to enrich essence with Guilu Erxian Decoction,benefiting qi to promote fluid production with Buzhong Yiqi Decoction,and warming yang and transporting fluids with Xianfu Shezi Decoction should be considered.Medication and dosage adjustments should be made based on the specific etiology,pathology,and related symptoms to improve the quality of male sperm and enhance the chances of conception.

Objective To investigate the effect and mechanism of transplantation of neuregulin1(NRG1)gene-modified bone marrow mesenchymal stem cells(BMSCs)on the repair of hemi-transected spinal cord injury(SCI)in rats.Methods Isolated and cultured rat BMSCs,followed by transfection with the NRG1 gene.The levels of NRG1 in BMSCs lysate and culture supernatant was deected by ELISA method,and the proliferation activity of the BMSCs was detected by cell counting method.Forty-three healthy 8-week-old SD rats were randomly divided into control group(n=10),SCI model group(n=10),BMSCs group(n=10),and NRG1-BMSCs group(n=13).After establishing the spinal cord hemisection model,animals received in-situ transplantation of BMSCs or NRG1-BMSCs.On the 1,7,14,21,and 28 days after transplantation,the hind limb motor function was evaluated using BBB score and inclined plate test;on the 7th day after transplantation,the migration and distribution of transplanted cells was monitored using a fluorescence microscope;on the 28th day after transplantation,the pathological changes of rat spinal cord tissues was examined using HE staining and Nissl staining;cell apoptosis using TUNEL staining,and levels of endoplasmic reticulum stress-related proteins[X-box binding protein 1(XBP1),C/EBP homologous protein(CHOP),activating transcription factor 4(ATF4),ATF6,glucose-regulated protein 78(GRP78)]and apoptosis-related proteins[B-cell lymphoma-2(Bcl-2)and Bcl-2-associated protein X(Bax)]in rat spinal cord tissues using Western blotting.Results BMSCs were successfully isolated,cultured,and transfected with the NRG1 gene.ELISA method results showed that the NRG1 contents in the NRG1-BMSCs lysate and culture supernatant were significantly higher than that of BMSCs in a time-dependent manner(P<0.05).The proliferation activity of NRG1-BMSCs was significantly higher than that of BMSCs(P<0.05).On the 21 and 28 days after transplantation,the BBB score and the slope angle of the inclined plate in NRG1-BMSCs group were higher than those in SCI model group or BMSCs group(P<0.05).However,it did not reverse to the level in control group(P<0.05).On the 28th day after transplantation,compared with the SCI model group and BMSCs group,neuronal pyknosis reduced,the Nissl body density increased,the expression levels of XBP1,CHOP,ATF4,ATF6,GRP78,and Bax,and the rate of TUNEL-positive cells significantly reduced in NRG1-BMSCs group(P<0.05),and the expression level of Bcl-2 significantly increased(P<0.05).Conclusion Transplantation of NRG1 gene-modified BMSCs can alleviate SCI and improve the recovery of motor function in rats.The mechanism may be related to promoting the proliferation activity of BMSCs,inhibiting cell apoptosis,and mitigating endoplasmic reticulum stress.

ObjectiveIn recent years, the negative impact of microgravity on astronauts’ nervous systems has received widespread attention. The repetitive transcranial magnetic stimulation (rTMS) technology has shown significant positive effects in the treatment of neurological and psychiatric disorders. The potential benefits of combined frequency stimulation (CFS) which combines different frequency stimulation patterns in ameliorating neurological dysfunctions induced by the microgravity environment, still require in-depth investigation. Exploring the therapeutic effects and electrophysiological mechanisms of CFS in improving various neurological disorders caused by microgravity holds significant importance for neuroscience and the clinical application of magnetic stimulation. MethodsThis study employed 40 C57BL/6 mice, randomly divided into 5 groups: sham group, hindlimb unloading (HU) group, 10 Hz group, 20 Hz group, and combined frequency stimulation (10 Hz+20 Hz, CFS) group. Mice in all groups except the sham group received 14 d of simulated microgravity conditions along with 14 d of repetitive transcranial magnetic stimulation. The effects of CFS on negative emotions and spatial cognitive abilities were assessed through sucrose preference tests and water maze experiments. Finally, patch-clamp techniques were used to record action potentials, resting membrane potentials, and ion channel dynamics of granule neurons in the hippocampal dentate gyrus (DG) region. ResultsCompared to the single-frequency stimulation group, behavioral results indicated that the combined frequency stimulation (10 Hz+20 Hz) significantly improved cognitive impairments and negative emotions in simulated microgravity mice. Electrophysiological experiments revealed a decrease in excitability of granule neurons in the hippocampal DG region after HU manipulation, whereas the combined frequency stimulation notably enhanced neuronal excitability and improved the dynamic characteristics of voltage-gated Na⁺ and K⁺ channels. ConclusionThe repetitive transcranial magnetic stimulation with combined frequencies (10 Hz+20 Hz) effectively ameliorates cognitive impairments and negative emotions in simulated microgravity mice. This improvement is likely attributed to the influence of combined frequency stimulation on neuronal excitability and the dynamic characteristics of Na⁺ and K⁺ channels. Consequently, this study holds the promise to provide a theoretical basis for alleviating cognitive and emotional disorders induced by microgravity environments.

Objective To explore the effect of Qingre Xiaoyanning tablets on chronic toxicity in SD rats.Methods A total of 120 SD rats were randomly divided into blank group(water)and experimental-L,-M,-H groups(2.63,5.25 and 10.50 g·kg 1 Qingre Xiaoyanning dry paste powder),with 30 rats per group.Four groups were administered continuously for 4 weeks with a recovery period of 4 weeks.SD rats were dissected as planned.The general condition,weight gain,hematological and biochemical indexes,major organ coefficients,macroscopic and microscopic tissue morphology were observed.Results There were no significant differences in the general condition,body mass growth,coagulation index and histopathology of rats between the experimental-L,-M,-H groups and the blank group.End of administration,the mean hemoglobin concentrations of experimental-H and blank groups were(370.70±3.78)and(365.90±5.77)g·L-1,glucose were(5.98±0.63)and(6.61±0.93)mmol·L-1,blood urea nitrogen(BUN)were(4.72±1.01)and(5.78±1.64)mmol·L-1,liver coefficients were 3.05±0.17 and 2.89±0.19,and the differences were statistically significant(P≤0.05,P≤0.01).Resumption of the final,direct bilirubin of experimental-L and blank groups were(0.38±0.18)and(0.19±0.18)pmol·L 1,BUN of experimental-M and blank groups were(4.45±0.56)and(5.65±1.16)mmol·L-1,and the differences were statistically significant(all P≤0.05).Conclusion Repeated administration of Qingre Xiaoyanning tablets showed no significant toxicity in SD rats.

Inflammasome is a kind of intracellular polyprotein complex,which is an important component of the complex system of local inflammatory microenvironment after human tissue damage.When the inflammasome is activated,it induces the activation of cysteine aspartate proteinase 1(caspase-1),mediates the maturation and secretion of proinflammatory cytokines,such as interleukin(IL)-1 β and IL-18,and induces cell death,which plays an important role in regulating the host immune response to pathogen infection and tissue repair of cell damage.Nod-like receptor protein 3(NLRP3)inflammatory body,which is composed of NLRP3,pro-cysteine aspartic acid specific protease-1(pro-caspase-1)and apoptosis-related spot-like protein(ASC),is the most deeply and widely studied type of inflammatory body,which plays an important role in the regulation of inflammation.When NLRP3 inflammatory bodies are activated,inflammatory mediators are produced and released,which participate in the occurrence and development of a variety of inflammatory diseases.Some studies have shown that traditional Chinese medicine can improve the pathological state of a variety of diseases by inhibiting NLRP3 inflammatory bodies,and play a role in the prevention and treatment of a variety of inflammatory diseases,including cardiovascular diseases,joint inflammation,diabetes and so on.This paper systematically combs the mechanism of NLRP3 inflammatory bodies,and summarizes the latest research reports on the effects of traditional Chinese medicine compound prescription,traditional Chinese medicine monomers and traditional Chinese medicine extracts on NLRP3 inflammatory bodies in the treatment of inflammatory diseases,in order to provide new ideas for the further study of the pathogenesis and drug treatment of many inflammatory diseases.