Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Ovarian tissue cryopreservation and transplantation is currently the only feasible method for preserving both fertility and ovarian endocrine function in prepubertal female patients. It is indicated for those requiring gonadotoxic therapies such as chemo-therapy, radiotherapy, or bone marrow transplantation for malignant diseases, as well as for non-malignant diseases, including immunologic, metabolic, and hematologic benign diseases requiring bone marrow transplantation, and other populations at high risk of premature ovarian insufficiency. The procedure involves laparoscopic retrieval of ovarian tissue, typically via unilateral oophorectomy in young patients, followed by slow-programmed cryopreservation. When the primary disease is cured and fertility or hormonal function restoration is desired, the tissue is thawed and transplanted, most commonly to an orthotopic site. For patients at high risk of ovarian malignancy involvement, pre-transplantation assessment of minimal residual disease in the ovarian cortex is performed using histo-pathology and molecular biology techniques. Globally, while ovarian tissue cryopreservation and transplantation has led to over 300 live births, the majority result from tissue cryopreserved after puberty. Successful restoration of puberty and subsequent live births following transplantation of tissue frozen before puberty, although demonstrated in reported cases, remain less common. Therefore, this review systematically summarizes recent advances in the indications, current application status, timing and strategies of ovarian tissue cryopreservation and transplantation, risk assessment of tumor cell reintroduction, and clinical outcomes in prepubertal patients. It also discusses the potential value and current challenges of combining this approach with invitro oocyte maturation techniques, ainming to provide practical references for clinical practice.

Objective To evaluate the impact of slow-freezing process on human ovarian tissue with the standard cryopreservation-thawing protocol of Fertility Protection Center of Beijing Obstetrics and Gynecology Hospital,Capital Medical University.Methods Ovarian tissues of 12 patients were divided into fresh ovarian tissue group(fresh group)and freezing-thawing ovarian tissue group(F-T group).The freezing-thawing protocol was the standard protocol in our center.The number and activity of follicle were examined with Hematoxylin-eosin(HE)staining and calcein-AM(calcein acetoxymethylester)staining,and the proliferation and apoptosis was evaluated with the immunohistochemical staining of Ki-67 and caspase-3.The expressions of apoptosis-related proteins such as caspase-3,bax and FasL between the two groups were compared with Western blotting.Results There were no statistically significant differences in follicle counting and follicle activity in ovarian tissues pre-and post-freezing-thawing(P>0.05),and the positive rate of Ki-67 in ovarian tissues after freezing-thawing was significantly lower than that in fresh ovarian tissues(P<0.05),and there was no statistically significant difference in the positive rate of caspase-3 between the two groups(P>0.05).The expression of caspase-3 protein in ovarian tissues after freezing-thawing was significantly higher than that in fresh ovarian tissues(P<0.05),while the expressions of other apoptosis-related proteins such as bax and FasL were not significantly different(P>0.05).Conclusion The standard cryopreservation-thawing regimen in our center can effectively maintain the follicle number,morphology,and activity in ovarian tissues.After freezing and thawing,the cell proliferation level is decreased.The expression of apoptosis-related proteins such as bax and FasL are not increased,and the expression of caspase-3 is relatively increased.These results suggest our freezing-thawing regimen is good for human ovarian tissue.

Female infertility is recognized as a global public health issue by the World Health Organization.Female fertility remodeling includes ovarian function reconstruction and uterus/endometrium reconstruction,etc.It is emerging as a hot technology since it is ready to prepare autologous platelet-rich concentrate and it is safer and more acceptable in autologous application.It plays an important role in regenerative medicine,and it is currently widely applied in maxillofacial and plastic surgery,dermatology and other clinical practices.This article mainly reviews the progresses of the application of autologous platelet-rich concentrate in female fertility remodeling.

Objective To evaluate the impact of slow-freezing process on human ovarian tissue with the standard cryopreservation-thawing protocol of Fertility Protection Center of Beijing Obstetrics and Gynecology Hospital,Capital Medical University.Methods Ovarian tissues of 12 patients were divided into fresh ovarian tissue group(fresh group)and freezing-thawing ovarian tissue group(F-T group).The freezing-thawing protocol was the standard protocol in our center.The number and activity of follicle were examined with Hematoxylin-eosin(HE)staining and calcein-AM(calcein acetoxymethylester)staining,and the proliferation and apoptosis was evaluated with the immunohistochemical staining of Ki-67 and caspase-3.The expressions of apoptosis-related proteins such as caspase-3,bax and FasL between the two groups were compared with Western blotting.Results There were no statistically significant differences in follicle counting and follicle activity in ovarian tissues pre-and post-freezing-thawing(P>0.05),and the positive rate of Ki-67 in ovarian tissues after freezing-thawing was significantly lower than that in fresh ovarian tissues(P<0.05),and there was no statistically significant difference in the positive rate of caspase-3 between the two groups(P>0.05).The expression of caspase-3 protein in ovarian tissues after freezing-thawing was significantly higher than that in fresh ovarian tissues(P<0.05),while the expressions of other apoptosis-related proteins such as bax and FasL were not significantly different(P>0.05).Conclusion The standard cryopreservation-thawing regimen in our center can effectively maintain the follicle number,morphology,and activity in ovarian tissues.After freezing and thawing,the cell proliferation level is decreased.The expression of apoptosis-related proteins such as bax and FasL are not increased,and the expression of caspase-3 is relatively increased.These results suggest our freezing-thawing regimen is good for human ovarian tissue.

Objective:To investigate the management of cancer pain and the clinical practices of hospice care across 11 cities in Zhejiang Province.Methods:From May 22 to 29, 2023, the Zhejiang Provincial Health Commission conducted a survey to assess the current status of hospice care practitioners regarding cancer pain management, the practices employed by medical staff in managing cancer pain, and the understanding of medical personnel concerning self-controlled analgesia for cancer pain treatment in Zhejiang Province.Results:A total of 505 questionnaires were collected from 198 hospitals across 11 cities in the province.Among the medical staff in secondary and tertiary medical institutions, 85.71%(198 out of 231)participated in the management of cancer pain in patients.Oral analgesics emerged as the most commonly used treatment for pain outbreaks, accounting for 38.53%(89 out of 231)of cases.Additionally, 37.66%(87 out of 231)of medical personnel were involved in the development of self-controlled analgesia devices within their institutions.Conclusions:In the management of cancer pain within hospice care, it is essential to enhance the theoretical training of medical staff, ensure the availability of basic analgesic medications, and establish standardized management protocols for the entire process as promptly as possible.

Female infertility is recognized as a global public health issue by the World Health Organization.Female fertility remodeling includes ovarian function reconstruction and uterus/endometrium reconstruction,etc.It is emerging as a hot technology since it is ready to prepare autologous platelet-rich concentrate and it is safer and more acceptable in autologous application.It plays an important role in regenerative medicine,and it is currently widely applied in maxillofacial and plastic surgery,dermatology and other clinical practices.This article mainly reviews the progresses of the application of autologous platelet-rich concentrate in female fertility remodeling.

Objective:A preliminary trial is conducted to explore whether perioperative(preoperative,intraoperative,and postoperative)electroacupuncture is more effective than postoperative electroacupuncture in improving gastrointestinal function for colorectal cancer patients.Methods and analysis:The study proposes a randomized,parallel-controlled,single-center trial involving 30 colorectal cancer patients aged 18-79 requiring elective surgery.Participants are randomly assigned to two groups,with equal allocation,where one group receives perioperative electroacupuncture,and the other group receives postoperative electroacupuncture.The treatment duration spans from preoperative to postoperative 72 h,with a subsequent 28-day follow-up period.The primary outcome is the time of first postoperative defecation.The secondary outcomes include the recovery time of postoperative bowel sounds,time of the first flatus,dietary recovery,postoperative gastrointestinal dysfunction frequency,quality of life scale,postoperative pain degree,time of the first ambulation,length of hospital stay,gastrointestinal hormone indicators,and adverse events.The coagulation function test,liver and renal function,and stool and blood routine serve as security biomarkers.The statistical analysis includes the t-test,rank-sum test,Chi-square test,and analysis of variance.A two-sided significance level is set at 5%.Discussion:This study aims to evaluate the feasibility and preliminary effectiveness of perioperative electroacupuncture for gastrointestinal function recovery following colorectal cancer surgery.The study's strengths include its randomized design,well-defined intervention periods,and multi-dimensional outcome assessment.Nevertheless,limitations,such as the small sample size and single-center setting,may affect external validity.The findings will guide protocol refinement and sample size estimation for future large-scale multi-center randomized controlled trials.

Objective:A preliminary trial is conducted to explore whether perioperative(preoperative,intraoperative,and postoperative)electroacupuncture is more effective than postoperative electroacupuncture in improving gastrointestinal function for colorectal cancer patients.Methods and analysis:The study proposes a randomized,parallel-controlled,single-center trial involving 30 colorectal cancer patients aged 18-79 requiring elective surgery.Participants are randomly assigned to two groups,with equal allocation,where one group receives perioperative electroacupuncture,and the other group receives postoperative electroacupuncture.The treatment duration spans from preoperative to postoperative 72 h,with a subsequent 28-day follow-up period.The primary outcome is the time of first postoperative defecation.The secondary outcomes include the recovery time of postoperative bowel sounds,time of the first flatus,dietary recovery,postoperative gastrointestinal dysfunction frequency,quality of life scale,postoperative pain degree,time of the first ambulation,length of hospital stay,gastrointestinal hormone indicators,and adverse events.The coagulation function test,liver and renal function,and stool and blood routine serve as security biomarkers.The statistical analysis includes the t-test,rank-sum test,Chi-square test,and analysis of variance.A two-sided significance level is set at 5%.Discussion:This study aims to evaluate the feasibility and preliminary effectiveness of perioperative electroacupuncture for gastrointestinal function recovery following colorectal cancer surgery.The study's strengths include its randomized design,well-defined intervention periods,and multi-dimensional outcome assessment.Nevertheless,limitations,such as the small sample size and single-center setting,may affect external validity.The findings will guide protocol refinement and sample size estimation for future large-scale multi-center randomized controlled trials.

Objective:To investigate the management of cancer pain and the clinical practices of hospice care across 11 cities in Zhejiang Province.Methods:From May 22 to 29, 2023, the Zhejiang Provincial Health Commission conducted a survey to assess the current status of hospice care practitioners regarding cancer pain management, the practices employed by medical staff in managing cancer pain, and the understanding of medical personnel concerning self-controlled analgesia for cancer pain treatment in Zhejiang Province.Results:A total of 505 questionnaires were collected from 198 hospitals across 11 cities in the province.Among the medical staff in secondary and tertiary medical institutions, 85.71%(198 out of 231)participated in the management of cancer pain in patients.Oral analgesics emerged as the most commonly used treatment for pain outbreaks, accounting for 38.53%(89 out of 231)of cases.Additionally, 37.66%(87 out of 231)of medical personnel were involved in the development of self-controlled analgesia devices within their institutions.Conclusions:In the management of cancer pain within hospice care, it is essential to enhance the theoretical training of medical staff, ensure the availability of basic analgesic medications, and establish standardized management protocols for the entire process as promptly as possible.