Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting a substantial proportion of women of reproductive age. It is frequently associated with ovulatory dysfunction, infertility, and an increased risk of chronic metabolic diseases. A hallmark pathological feature of PCOS is the arrest of follicular development, closely linked to impaired intercellular communication between the oocyte and surrounding granulosa cells. Transzonal projections (TZPs) are specialized cytoplasmic extensions derived from granulosa cells that penetrate the zona pellucida to establish direct contact with the oocyte. These structures serve as essential conduits for the transfer of metabolites, signaling molecules (e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β‑catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.

Mitophagy, a highly precise form of autophagy, plays a pivotal role in maintaining cellular homeostasis by selectively targeting and eliminating damaged mitochondria through a process known as mitophagy. Within this tightly regulated mechanism, dysfunctional mitochondria are specifically delivered to lysosomes for degradation. Disruptions in mitophagy have been implicated in a diverse range of pathological conditions, spanning diseases of the nervous system, cardiovascular system, cancer, aging, and metabolic syndrome. The elucidation of mitophagy’s impact on cardiovascular disorders, liver diseases, metabolic syndromes, immune dysfunctions, inflammatory conditions, and cancer has significantly advanced our understanding of the complex pathogenesis underlying these conditions. These studies have shed light on the intricate connections between dysfunctional mitophagy and disease progression. Among the disorders associated with mitochondrial dysfunction, insulin resistance (IR) stands out as a prominent condition linked to metabolic disorders. IR is characterized by a diminished response to normal levels of insulin, necessitating higher insulin levels to trigger a typical physiological reaction. Hyperinsulinemia and metabolic disturbances often coexist with IR, primarily due to defects in insulin signal transduction. Oxidative stress, stemming from mitochondrial dysfunction, exerts dual effects in the context of IR. Initially, it disrupts insulin signaling pathways and subtly contributes to the development of IR. Additionally, by inducing mitochondrial damage and autophagy, oxidative stress indirectly impedes insulin signaling pathways. Consequently, mitophagy acts as a protective mechanism, encapsulating damaged or dysfunctional mitochondria through the autophagy-lysosome pathway. This efficient process eliminates excessive oxidative stress reactive. The intricate interplay between mitochondrial function, oxidative stress, mitophagy, and IR represents a captivating field of investigation in the realm of metabolic disorders. By unraveling the underlying complexities and comprehending the intricate relationships between these intertwined processes, researchers strive toward uncovering novel therapeutic strategies. With a particular focus on mitochondrial quality control and the maintenance of redox homeostasis, these interventions hold tremendous potential in mitigating IR and enhancing overall metabolic health. Emerging evidence from a myriad of studies has shed light on the active involvement of mitophagy in the pathogenesis of metabolic disorders. Notably, interventions such as exercise, drug therapies, and natural products have been documented to induce mitophagy, thereby exerting beneficial effects on metabolic health through the activation of diverse signaling pathways. Several pivotal signaling molecules, including AMPK, PINK1/Parkin, BNIP3/Nix, and FUNDC1, have been identified as key regulators of mitophagy and have been implicated in the favorable outcomes observed in metabolic disorders. Of particular interest is the unique role of PINK1/Parkin in mitophagy compared to other proteins involved in this process. PINK1/Parkin exerts influence on mitophagy through the ubiquitination of outer mitochondrial membrane proteins. Conversely, BNIP3/Nix and FUNDC1 modulate mitophagy through their interaction with LC3, while also displaying certain interrelationships with each other. In this comprehensive review, our objective is to investigate the intricate interplay between mitophagy and IR, elucidating the relevant signaling pathways and exploring the treatment strategies that have garnered attention in recent years. By assimilating and integrating these findings, we aim to establish a comprehensive understanding of the multifaceted roles and intricate mechanisms by which mitophagy influences IR. This endeavor, in turn, seeks to provide novel insights and serve as a catalyst for further research in the pursuit of innovative treatments targeting IR.

Di-(2-ethylhexyl) phthalate (DEHP) is currently one of the most widely used plasticizers, widely found in all kinds of items, such as children’s toys and food packaging materials, but also added to wallpaper, cable protective agents and other building decoration materials. DEHP is toxic and absorbed by the human body through respiratory tract, digestive tract and skin contact, which can cause damage to multiple systems, especially the male reproductive system, and testis is an important target organ. Oxidative stress injury is the core mechanism of spermatogenesis disorder caused by DEHP. DEHP exposure can cause oxidative stress or reactive oxygen species (ROS) increase in germ cells, and on this basis, promote cell apoptosis or cause excessive autophagy. The toxicity of DEHP to Leydig cells is mainly to interfere with the synthesis of steroid hormones. For Sertoli cells, ferroptosis and destruction of the blood-testis barrier are common injury mechanisms. In addition, gene methylation caused by DEHP not only affects the spermatogenic process, but also has epigenetic effects on offspring. In this paper, we reviewed the pathological damage, germ cell toxicity and epigenetic effects of DEHP on testis, and focused on the damage and molecular mechanism on testicular spermatogenic cells, Leydig cells and Sertoli cells. Future research is required to elucidate the body’s clearance mechanism and treatment plan after exposure to DEHP and whether DEHP will damage the function of myoid cells. It is hoped that this can provide new ideas for prevention and treatment of male reproductive disorders resulting from long-term exposure to plastic products.

Objective To investigate the effects of microsurgical varicocelectomy on testicular function and sexual function in patients with varicocele.Methods The clinical data of 90 patients with varicocele admitted to our hospital were retrospectively analyzed,and the patients were divided into the laparoscopic group(received laparoscopic varicocelectomy)and the microscopic group(received microsurgical varicocelectomy)according to different surgical methods,with 45 cases in each group.The testicular function and sexual function related indexes including sperm density,normal sperm ratio,rate of sperm motility(grades a+b),forward motility sperm rate,international index of erectile function-5(IIEF-5)score,and the levels of testosterone,follicle-stimulating hormone,luteinizing hormone,and androgen levels before and 6 months after surgery in the two groups were compared.The incidence of complications and recurrence 6 months after surgery in the two groups were counted.Results Compared with those before surgery,the sperm density,forward motility sperm rate,rate of sperm motility(grades a+b),normal sperm ratio,IIEF-5 score,testosterone level,and androgen level 6 months after surgery of patients in the two groups were significantly increased(P<0.05),and the levels of luteinizing hormone and follicle-stimulating hormone were decreased(P<0.05).Compared with the laparoscopic group,the levels of follicle-stimulating hormone and luteinizing hormone,and incidence of complications 6 months after surgery of patients in the microscopic group were decreased(P<0.05),and the levels of testosterone and androgens,and IIEF-5 score 6 months after surgery were increased(P<0.05).There was no significant difference in the recurrence rate between the two groups(P>0.05).Conclusion Microsurgical varicocelectomy can improve the testicular function and sexual function of patients with varicocele,with a low incidence of complications.

On August 2-4,2023,the"Third Summit Forum on'Building a Community of Shared Future for Doctors and Patients'"was jointly organized by institutions such as the Chinese Medical Ethics,the Hospital Humanities Management and Talent Training Special Committee of the China Population and Culture Promotion Association,Center for Ethical Studies of Renmin University of China,the Newspaper for China's Physicians,the China Health Law Society,the China Anti-Cancer Association,and the China Association For Ethical Studies in Harbin.The conference arranged a sub-forum for the"Seminar on the Construction of Chinese Medical Humanities",with domestic medical humanities scholars attending the conference.After heated discussions at the seminar,the Scholars'Consensus on the Construction and Development of Chinese Medical Humanities was formed.It was proposed that in the new era,it is urgent to build the medical humanities discipline,as well as lead the academic integration and development of medical humanities under the core socialist values.At the same time,for the construction of the medical humanities discipline,it is necessary to optimize the organizational mechanism,prosper and develop the overall framework of the medical humanities discipline,accelerate the construction of a professional teaching team for the medical humanities discipline,promote the establishment of a new carrier medical humanities education and teaching in cultivating morality and nurturing talents,as well as focus on solving problems related to the cultivation of medical humanities graduate students.

Platelets have long been recognized as key players in hemostasis and thrombosis; however, there is growing evidence that they are also involved in cancer. Preclinical and clinical studies have shown that platelets can promote tumorigenesis and metastasis through various crosstalks between platelets and cancer cells. Platelets play an active role in all stages of tumorigenesis, including tumor growth, tumor cell extravasation, and metastasis. In addition, thrombocytosis in cancer patients is associated with poor patient survival. Platelets are also well-placed to coordinate local and distant tumor-host interactions due to the a- bundance of microparticles and exosomes. Therefore, antitumor drugs targeting platelets have great development and application prospects. The following will review the research progress of anti-tumor drugs targeting platelets.

Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Purpose::The reconstruction of Allen's type IV fingertip amputation is a clinical challenge. Our team designed bilateral unequal-sized hallux osteo-onychocutaneous free flaps for the long-term reconstruction of Allen's type IV fingertip amputation and conducted a retrospective study with a 5-year follow-up aims to evaluate the effects of this technique.Methods::A retrospective analysis with a 5-year follow-up including 13 patients with Allen's type IV fingertip amputation who were admitted to our hospital from January 2010 to January 2017 was conducted. The patients were treated with bilateral unequal-sized hallux osteo-onychocutaneous free flaps. The operation time, intraoperative blood loss, and complications were recorded, and the survival rate of the transplanted flaps was calculated. During the 5-year follow-up after operation, the nail growth time was recorded and the finger appearance was observed. At the last follow-up appointment, the length, width, and girth of the reconstructed fingertip and contralateral normal fingertip, range of motion of the reconstructed fingertip and contralateral normal fingertip, Semmes-Weinstein test (for the evaluation of tactile sensation), and two-point discrimination testing results were recorded. SPSS 22.0 software was used for the statistical analysis and the data are presented as mean ± SD.Results::The mean operation time was (5.62 ± 0.51) h, the mean intraoperative blood loss was (34.15 ± 3.13) mL, and the survival rate of the transplanted flaps was 100%. During the 5-year follow-up, the average nail growth time was (10.14 ± 1.98) months and the average bone union time was (3.78 ± 0.91) months. The length, width, and girth of the reconstructed fingertip were (31.52 ± 3.73) mm, (17.82 ± 1.74) mm, and (59.75 ± 3.04) mm, respectively, which did not differ from those of the contralateral normal fingertip. The range of motion of the reconstructed fingertip was (12.15 ± 2.79) degrees which is different from that of the contralateral normal fingertip. The average tactile sensation evaluated via the Semmes-Weinstein test and the average two-point discrimination test of the reconstructed fingertip were (0.39 ± 0.17) g and (7.46 ± 1.14) mm, respectively, which were not different from those of the contralateral normal fingertip. The average Maryland score of feet in the donor area was 87.66 ± 7.39, which was satisfactory.Conclusion::Bilateral unequal-sized hallux osteo-onychocutaneous free flaps are an effective method to reconstruct Allen's type IV fingertip amputations with a satisfactory appearance and good sensory function.

Objective To study the effects of different SBRT-VMAT plans for non-small cell lung cancer(NSCLC)with unilateral ipsilateral double metastatic lesions on received dose,monitor unit(MU),conformity index(CI)and gradient index(GI)of the lung,so as to provide references for therapy planning of the patient above.Methods A total of 11 NSCLC patients with unilateral ipsilateral double metastatic lesions were selected,with three plans developed for each patient by the volumetric modulated arc therapy(VMAT).The inner target areas ITV1 and ITV2 were contoured based on the maximum projection image of the 4D-CT localization mode,which were uniformly expanded externally by 3 mm to obtain the plan target area PTV1 and PTV2,and then PTV1 was added with PTV2 to get PTV12.The first planning mode had the centers of PTV1 and PTV2 target areas as the treatment centers,and two separate plans of plan-1 and plan-2 were developed and then combined into a plan-sum plan for dose evaluation;the second planning mode had the centers of PTV1 and PTV2 target areas as the treatment center,resepctively,and a multicenter plan(plan-D)was formed.The third planning mode had the center of PTV12 target area as the treatment center,and a single-center plan(plan-S)was designed.To meet the requirements of prescribed dose,plan-1 and plan-2 of plan-sum were normalized to PTV1 and PTV2 95％volume and plan-S and plan-D were normalized to PTV 12 95％volume.The three planning modes were compared in terms of received dose,MU,CI and GI of the lung.SPSS 25.0 software was carried out for statistical analysis.Results Plan-S had no significant differences with Plan-sum except V5(P＞0.05),whose V10,V20,V30 and mean dose were significantly lower than those of plan-sum(P＜0.05);plan-D had its received dose and mean dose statistically lower than those of plan-sum(P＜0.05);plan-S and plan-D had no obvious differences in received dose of the lung(P＞0.05).Plan-sum had the CI significantly lower than those of plan-S and plan-D(P＜0.05);plan-S and plan-D had no statistically differences in CI(P＞0.05).Plan-D had the GI significantly lower than plan-S and plan-sum(P＜0.05).Plan-S and plan-sum had no significant differences in GI(P＞0.05).Plan-D and plan-sum had no statistical differences in MU(P＞0.05),which had the MUs significantly higher than that of plan-S(P＜0.05).Conclusion A multicenter planning mode may be used for optimizing dose distribution and enhancing conformity in case the patient can tolerate prolonged immobilization in a fixed position,and a singlecenter planning mode should be adopted to shorten treatment time when the patient is in poor physical conditions.[Chinese Medical Equipment Journal,2024,45(10):49-53]