Decreased endometrial receptivity is a critical factor contributing to the decline in fertility among women of advanced age. With the increase of age, the endometrium exhibits diminished hormonal responsiveness, a phenomenon known as inflammaging, and an imbalance in immune cell populations. These changes impede the processes of endometrial epithelial-mesenchymal transition and decidualization, thereby negatively impacting embryo implantation and reducing overall fertility potential. Furthermore, adverse lifestyle choices, exposure to environmental factors, inflammatory conditions, and repeated interventions within the uterine cavity can result in pathological aging of the endometrium that does not align with its chronological age. This misalignment may be associated with the emergence of various reproductive disorders, even in younger women. This paper seeks to investigate the relationship between pathological aging of the endometrium and reproductive disorders, particularly in the context of embryo implantation, with the aim of providing new insights into the pathogenesis, clinical diagnosis, and treatment of reproductive disorders.

ObjectiveTo explore the possible mechanisms of Wenyang Huazhuo Formula （温阳化浊方， WHF） in improving reproductive aging from the perspective of the ovarian mechanical microenvironment. MethodsThe experiment included five groups， 3-month group （20 female mice at 3 months of age）， 6-month group （20 female mice at 6 months of age）， 6-month + WHF group （20 female mice at 5 months of age treated with WHF）， 9-month group （20 female mice at 9 months of age）， and 9-month + WHF group （20 female mice at 8 months of age treated with WHF）. The 6-month + WHF group and 9-month + WHF group were orally administered WHF 41.2 g/（kg·d） once daily for 4 consecutive weeks. The other three groups received no intervention. Reproductive hormone levels were measured by ELISA. HE staining was used to count the numbers of various stages of follicles. Ovarian hyaluronic acid （HA） content and collagen fiber content were measured to evaluate the ovarian mechanical microenvironment. Superovulation was performed to observe the number of eggs obtained， as well as the number of offspring and birth weight to assess fertility. The in vitro fertilization and blastocyst culture of oocytes from female offspring in each group were observed to evaluate the effect of WHF on offspring reproductive potential. ResultsCompared with the 3-month group， the 6-month group and 9-month group showed significantly decreased serum levels of gonadotropin-releasing hormone （GnRH）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH）， decreased ovarian collagen content， and reduced numbers of primordial and secondary follicles. In contrast， the numbers of primary follicles， antral follicles， and atretic follicles increased. The levels of anti-Müllerian hormone （AMH）， ovarian HA content， and the fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring were significantly lower （P＜0.05）. Compared with the 6-month group， the 6-month + WHF group showed significantly reduced serum levels of GnRH， FSH， and LH， with a significant decrease in primary follicles， antral follicles， and atretic follicles as well as increase of AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， and offspring birth weight （P＜0.05）. Compared with the 9-month group， the 9-month + WHF group exhibited reduced GnRH， FSH， and collagen fiber content， as well as reduced number of primary follicles， antral follicles， and atretic follicles. However， AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， offspring numbers， birth weight， fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring all significantly increased （P＜0.05）. ConclusionWHF can significantly improve the ovarian reserve， fertility， and reproductive potential in offspring during reproductive mid-life and late-life stages. Its effect may be related to the remodeling of the mechanical microenvironment of aging ovaries. Moreover， the effect on the mechanical microenvironment remodeling of late-stage ovaries and the improvement of the offspring reproductive potential is more significant.

Traditional Chinese medicine(TCM) processing is a unique and highly distinctive pharmaceutical technology in China. Utilizing modern scientific methods to elucidate the connotations of traditional processing theory and its effects is expected to facilitate the inheritance, development, innovation, and enhancement of TCM processing, and lead to more original research outcomes in the field of TCM. The breakthrough in TCM processing lies in the study of its underlying principles, and analyzing these principles involves researching the transformation mechanisms of chemical components and the biological effect mechanisms of the transformed components. This paper proposed the concept of "TCM processing chemical biology"(TCMPCB) for the first time. Under the guidance of TCM theory, the active components transformed during TCM processing were used as chemical tools to study their targets and molecular regulatory mechanisms, aiming to clarify the scientific principles by which TCM processing affected biological effects in the organism. The research findings also provided new directions for discovering novel active components, new lead compounds, creating new decoction pieces, and developing new TCM drugs. This paper provided a detailed introduction to the background, definition, research content, research ideas, research methods, and prospects of TCMPCB, with the aim of offering new research perspectives for analyzing the principles of TCM processing and providing new pathways for achieving the "four new and eight transformations" in TCM processing.
Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/methods* ; Humans ; Animals

A single-center, randomized, double-blind, dose-controlled trial of modified Sini Powder in treating mild to moderate generalized anxiety disorder(GAD) in the patients with syndrome of liver depression transforming into fire was conducted at Xiyuan Hospital, China Academy of Chinese Medical Sciences. A total of 80 patients with mild to moderate GAD and the syndrome of liver depression transforming into fire were included. Patients were assigned by the central randomization system at a ratio of 3∶1 into an observation group(n=60, receiving a conventional-dose of granules of modified Sini Powder) and a control group(n=20, receiving low-dose granules with the active ingredients being 50% of that in observation group). Assessments were conducted before treatment(baseline), after 2 weeks of introduction, after 2/4/8 weeks of treatment, and after 4 weeks of follow-up. The results were summarized as follows. In terms of primary outcome indicators, the observation group(62.2%) showed higher total response rate than the control group(26.6%)(P<0.05), and greater Hamilton anxiety scale(HAMA) score reduction after 8 weeks of treatment(P<0.05). In terms of secondary outcome indicators, the HAMA score(somatic anxiety score), traditional Chinese medicine(TCM) syndrome scores, Pittsburgh sleep quality index(PSQI) scale, and clinical global impression(CGI) scale score in the observation group showed a significant compared to the control group at each visit points(P<0.05). Adverse events occurred in 10 cases, including 9(16.9%) cases in the observation group and 1(6.6%) case in the control group. No adverse reaction was observed. In conclusion, conventional-dose modified Sini Powder demonstrated superior efficacy and favorable safety for mild and moderate GAD in the patients with the syndrome of liver depression transforming into fire over low-dose treatment.
Humans ; Male ; Female ; Adult ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/administration & dosage* ; Anxiety Disorders/drug therapy* ; Treatment Outcome ; Young Adult ; Powders ; Aged ; Liver/drug effects* ; Generalized Anxiety Disorder

Background Due to the unique working environment and numerous occupational disease hazards, workers in mining industry are particularly susceptible to psychological problems such as occupational stress. Objective To understand the current status of occupational stress, depressive symptoms, anxiety symptoms and sleep quality of workers in ferrous and non-ferrous metal mining industry in Gansu Province, and to explore the effects of occupational stress on depressive symptoms, anxiety symptoms, and sleep. Methods From April to December 2022, the workers of 25 large, medium, and small and micro enterprises were selected by stratified cluster random sampling and surveyed in ferrous and non-ferrous metal mining industry in Gansu Province. The Occupational Health Literacy Questionnaire of National Key Population, Core Occupational Stress Scale, Patient Health Questionnaire-q, Generalized Anxiety Disorder, and Self-administer Sleep Questionnaire were used to collect basic information, occupational stress, depressive symptoms, anxiety symptoms, and sleep quality of the workers. Chi-square test was used to compare occupational stress, depressive symptoms, anxiety symptoms and sleep disorders among different categories. Logistic regression model was used to study the effects of occupational stress on depressive symptoms, anxiety symptoms, and sleep quality. Results In this study, 2192 workers in mining industry were surveyed, of which 2087 returned valid questionnaires, and the recovery rate of valid questionnaires was 95.2%. Among them, 728 (38.4%) reported occupational stress. There were statistically significant differences in the positive rate of occupational stress among workers by gender, age, marital status, education level, average monthly income, length of service, enterprise size, and night shifts (P<0.001). The positive rates of depressive symptoms, anxiety symptoms, and sleep disorders in the mining industry workers were 85.6%, 49.8%, and 47.3%, respectively. The positive rates of depressive symptoms, anxiety symptoms, and sleep disorders among workers with higher occupational stress were higher than those among workers without occupational stress (P<0.001). The logistic regression analysis showed that occupational stress was a common risk factor for depressive symptoms (OR=3.29, 95%CI: 2.26, 4.79), anxiety symptoms (OR=2.87, 95%CI: 2.33, 3.53), and sleep disorder (OR=1.78, 95%CI: 1.46, 2.16). In addition, length of service and enterprise-scale were also risk factors for depressive symptoms, anxiety symptoms, and sleep disorders. In the 5−<10 and 10−<20 years of service groups, the risks of reporting depressive symptoms were 1.80 (95%CI: 1.18, 2.74) and 1.73 (95%CI: 1.10, 2.71) times higher than that of workers with less than 1 year of service, respectively; the risks of reporting anxiety symptoms were 1.98 (95%CI: 1.42, 2.76) and 2.11 (95%CI: 1.48, 3.01) times higher than that with less than 1 year of service, respectively; the risks of reporting sleep disorders were 1.58 (95%CI: 1.15, 2.16) and 1.78 (95%CI: 1.29, 2.45) times higher than that with less than 1 year of service, respectively. Workers in large enterprises were inclined to report more depressive symptoms, anxiety symptoms, and sleep disturbances than those in micro and small enterprises (OR=3.53, 95%CI: 2.41, 5.16; OR=2.49, 95%CI: 1.98, 3.13; OR=2.10, 95%CI: 1.67, 2.62). Conclusion The occupational stress level of mining industry workers in Gansu Province is high, and reporting occupational stress, 5−<10 and 10−<20 working age groups, and large enterprises are important risk factors affecting workers' mental health and sleep. It is necessary to increase the attention and develop intervention programs for mental health of miners in the working age group of 5−20 years old and in large enterprises.

Objective To identify the taste critical quality attribute and design and optimize the flavor-correcting formulation of the traditional Chinese medicine oral preparation Qingre Jiedu Oral Liquid,in order to improve its taste and enhance patient medication adherence.Methods The taste assignment method was employed to identify the taste critical quality attribute of Qingre Jiedu Oral Liquid.Based on human sensory evaluation and the standardized Euclidean distance in electronic tongue analysis,suitable types of corrigent were determined.Subsequently,under constraints such as maximum allowable dosage,solubility,and sweetness,the optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined using Box-Behnken experimental design combined with electronic tongue and human sensory evaluation results.The study was reviewed and approved by the Ethics Committee of Beijing University of Chinese Medicine(Ethics Approval Number 2020BZYLL0609).Results The quantitative score for bitter taste of Qingre Jiedu Oral Liquid accounted for 30.36%,confirming bitterness as the taste critical quality attribute requiring attention.The optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined to be 120 mg·mL?1 erythritol,12 mg·mL?1 acesulfame potassium,and 2.4 mg·mL?1 stevioside.This formulation achieved an 11.75-point improvement in sensory evaluation scores compared to the original commercially available oral liquid.Conclusion This study successfully improved the taste of Qingre Jiedu Oral Liquid and established a comprehensive strategy for flavor-correcting formulation optimization,including a method for identifying taste critical quality attribute.This strategy provides a referential paradigm for palatability enhancement of similar traditional Chinese medicine oral preparations,laying a crucial technical foundation for elevating the clinical value of Chinese herbal medicines and promoting the high-quality development of traditional Chinese medicine(TCM).

Objective:To investigate a new method for rapid detection of the MYOD1 L122R mutation and to analyze the clinical and pathological characteristics of mutation-positive rhabdomyosarcoma.Methods:A MYOD1 mutation detection kit was developed using allele-specific Taqman fluorescence probe technology. A total of 80 rhabdomyosarcoma samples diagnosed at Beijing Children′s Hospital, Capital Medical University from June 2022 to June 2023 were collected for testing. The detection sensitivity, specificity, and consistency rate of the kit were compared with those of the gold standard Sanger sequencing. The demographic, histopathological, and molecular genetic characteristics of patients with MYOD1 mutations were analyzed.Results:Among the 80 rhabdomyosarcoma cases, there were 46 males and 34 females, with an age of onset ranging from 0 to 16 years [mean (6.0±4.4) years], including 32 embryonal rhabdomyosarcoma, 18 alveolar rhabdomyosarcoma, and 30 spindle cell/sclerosing rhabdomyosarcoma. The new kit screened a total of 11 mutations, of which 10 were spindle cell/sclerosing rhabdomyosarcoma and one was embryonal rhabdomyosarcoma. Patients with MYOD1 mutations were typically older (four cases over 10 years old) but could also occur in young children (the youngest being 3-year and 2-month-old). The primary sites were the head and neck region in eight cases, limbs in two cases, and pelvic cavity in one case. Among the six patients with available staging information at initial diagnosis, one was classified as stage 2 and five were stage 3, all of which were intermediate risk. Among the 11 mutation patients, six had recurrence and metastasis, with three deaths; the remaining patients had not shown tumor progression until last follow-up. Compared with the wild type group, the expression level of MYOD1 in mutation patients increased significantly ( χ2=10.66, P=0.01), while the event-free survival rate ( χ2=9.925, P<0.01) and overall survival ( χ2=4.53, P=0.03) rate decreased. Compared with Sanger sequencing, the kit achieved 100% sensitivity and specificity. The kit had a minimum mutation content detection limit of 2% and the reaction could be finished within 2 hours. Additionally, this kit might also be used to detect the expression of MYOD1, thereby aiding the diagnosis of rhabdomyosarcoma. Conclusions:The study has established a new method for accurate and rapid detection of MYOD1 mutation in rhabdomyosarcoma, particularly suitable for the formalin-fixed and paraffin-embedded samples in clinical settings. MYOD1 mutations more likely occur in spindle cell/sclerosing rhabdomyosarcoma of the head and neck region in children. Patients with MYOD1 mutations have an extremely poor prognosis, which is independent of clinical staging and grading. MYOD1 mutation detection in rhabdomyosarcoma has significant value for auxiliary diagnosis and prognostic assessment.

Objective:To investigate a new method for rapid detection of the MYOD1 L122R mutation and to analyze the clinical and pathological characteristics of mutation-positive rhabdomyosarcoma.Methods:A MYOD1 mutation detection kit was developed using allele-specific Taqman fluorescence probe technology. A total of 80 rhabdomyosarcoma samples diagnosed at Beijing Children′s Hospital, Capital Medical University from June 2022 to June 2023 were collected for testing. The detection sensitivity, specificity, and consistency rate of the kit were compared with those of the gold standard Sanger sequencing. The demographic, histopathological, and molecular genetic characteristics of patients with MYOD1 mutations were analyzed.Results:Among the 80 rhabdomyosarcoma cases, there were 46 males and 34 females, with an age of onset ranging from 0 to 16 years [mean (6.0±4.4) years], including 32 embryonal rhabdomyosarcoma, 18 alveolar rhabdomyosarcoma, and 30 spindle cell/sclerosing rhabdomyosarcoma. The new kit screened a total of 11 mutations, of which 10 were spindle cell/sclerosing rhabdomyosarcoma and one was embryonal rhabdomyosarcoma. Patients with MYOD1 mutations were typically older (four cases over 10 years old) but could also occur in young children (the youngest being 3-year and 2-month-old). The primary sites were the head and neck region in eight cases, limbs in two cases, and pelvic cavity in one case. Among the six patients with available staging information at initial diagnosis, one was classified as stage 2 and five were stage 3, all of which were intermediate risk. Among the 11 mutation patients, six had recurrence and metastasis, with three deaths; the remaining patients had not shown tumor progression until last follow-up. Compared with the wild type group, the expression level of MYOD1 in mutation patients increased significantly ( χ2=10.66, P=0.01), while the event-free survival rate ( χ2=9.925, P<0.01) and overall survival ( χ2=4.53, P=0.03) rate decreased. Compared with Sanger sequencing, the kit achieved 100% sensitivity and specificity. The kit had a minimum mutation content detection limit of 2% and the reaction could be finished within 2 hours. Additionally, this kit might also be used to detect the expression of MYOD1, thereby aiding the diagnosis of rhabdomyosarcoma. Conclusions:The study has established a new method for accurate and rapid detection of MYOD1 mutation in rhabdomyosarcoma, particularly suitable for the formalin-fixed and paraffin-embedded samples in clinical settings. MYOD1 mutations more likely occur in spindle cell/sclerosing rhabdomyosarcoma of the head and neck region in children. Patients with MYOD1 mutations have an extremely poor prognosis, which is independent of clinical staging and grading. MYOD1 mutation detection in rhabdomyosarcoma has significant value for auxiliary diagnosis and prognostic assessment.

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

Objective:To explore the effect of tyrosine kinase inhibitor (TKI) dose reduction regimen in patients with chronic-phase chronic myeloid leukemia (CML) and its prognostic impact.Methods:A retrospective cohort study was conducted. The clinical data of patients with chronic-phase CML treated with reduced-dose TKI in the First Affiliated Hospital of Soochow University between January 2018 and December 2022 were collected. Patients were divided into groups based on Sokal score, European Treatment and Outcome Study long-term survival (ELTS) score, TKI drug classification and dose reduction, and treatment phase. The overall survival (OS), the cumulative incidence of major molecular response (MMR), the cumulative molecular recurrence rate and event-free survival (EFS) among patients in different strata were compared. Kaplan-Meier method was used for survival analysis.Results:Among 154 patients with chronic-phase CML, the median duration [ M ( IQR)] of reduced-dose TKI therapy was 35.4 months (34.9 months); Sokal score high-risk and low-/intermediate-risk groups comprised 20 cases (12.99%) and 134 cases (87.01%), respectively; ELTS score high-risk and low-/intermediate-risk groups comprised 14 cases (9.09%) and 140 cases (90.91%), respectively. Among 154 patients, 83 cases (53.90%) received imatinib therapy, while 71 cases (46.10%) received second-generation TKI; 138 patients (89.61%) maintained stable TKI dosing at the first dose level, and 16 patients (10.39%) maintained it at the second dose level. The induction therapy group comprised 33 patients (21.43%), while the maintenance therapy group included 121 patients (78.57%). The 3-year OS rate of all 154 patients was 90.6%. Patients in the Sokal score high-risk group demonstrated a lower 3-year OS rate compared to those in the low-/intermediate-risk group (64.1% vs. 96.7%) ( P < 0.001); patients in the ELTS score high-risk group had a lower 3-year OS rate compared to those in the low-/intermediate-risk group (62.9% vs. 95.8%) ( P = 0.002). There was no statistically significant difference in the 3-year OS rate of patients receiving the first dose level and those receiving the second dose level (90.6% vs. 90.0%, P = 0.478); there was no statistically significant difference in the 3-year OS rate of the induction therapy group and the maintenance therapy group (88.9% vs. 91.4%, P = 0.868). Among the 33 patients in the induction therapy group, all received the first dose level. After treatment, 28 achieved MMR, and 2 achieved molecular response 4.0 (MR4.0). The cumulative 1-year MMR rate of all patients in reduction therapy group was 95.8%, with a median time to MMR of 8.4 months; patients in the high-risk Sokal score group had a 1-year cumulative MMR rate of 50.0%, which was lower than that of the low-/intermediate-risk group (95.3%) ( P = 0.014); the median time to MMR was 14.7 months and 7.8 months, respectively. The cumulative 1-year MMR rate of patients treated with first-generation TKI was lower than that in those treated with second-generation TKI (65.0% vs. 100.0%, P = 0.034), and the median time to MMR of patients treated with first-generation TKI was longer than that those treated with second-generation TKI (9.1 months vs. 6.9 months). Among the 149 patients who achieved MMR, 5 experienced molecular relapse, resulting in a 3-year cumulative molecular relapse rate of 8.3%. In the Sokal score low-/intermediate-risk group, the 3-year cumulative molecular relapse rate (1.5% vs. 39.8%, P < 0.001), EFS rate (92.3% vs. 57.1%, P < 0.001), and OS rate (100.0% vs. 62.8%, P < 0.001) were better than those in the Sokal score high-risk group. The 3-year cumulative molecular relapse rate and 3-year EFS rate in patients receiving first dose level therapy were better than those in patients receiving second dose level therapy, and the differences were statistically significant (all P < 0.001). Conclusions:Patients with chronic-phase CML can still obtain good outcomes when receiving dose-reduced TKI, while the prognosis of patients in high-risk group is relatively poor. The choice of TKI and the dosage reduction should be individualized based on patients' characteristics.