BACKGROUND:Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells,promoting the phagocytosis of myelin debris by microvascular endothelial cells,affecting the migration and infiltration of microglia,promoting the recovery of damaged neurons,and decreasing neuronal apoptosis after spinal cord injury,but the mechanism of this is still not clear. OBJECTIVE:To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2(TREM2)and PI3K/Akt signaling pathways in mice following spinal cord injury. METHODS:Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group,a model group and a Wen-Shen-Tong-Du Decoction group,with 12 mice in each group.In the model and Wen-Shen-Tong-Du Decoction groups,mouse models of T10 spinal cord injury were prepared by the modified Allen's method.On the 1st day after modeling,the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage,and the sham-operation group and the model group were given saline by gavage once a day for 28 days.During the drug administration period,mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test.On the 7th and 28th days after modeling,hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice;immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1(IBA1)and TREM2;and western blot assay was used to detect the expression of TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,Bax and Caspase3 in spinal cord tissue. RESULTS AND CONCLUSION:Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury,and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury.Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group,manifesting as reduced degrees of dorsal white matter and neuronal atrophy,decreased cytoplasmic vacuolization,and reduced inflammatory cell infiltration.Immunofluorescence double staining results showed that on the 7th day after modeling,the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05);on the 28th day after modeling,the protein expression of TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05).Western blot results analysis demonstrated that on the 7th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,and Bcl2/Bax(P＜0.05),as well as a significant increase in p-Akt,Bax and p-Akt/Aktp-PI3K(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,p-PI3K/PI3K,p-Akt/Ak,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax and Caspase3 protein expression(P＜0.05).On the 28th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2 and Bcl2/Bax(P＜0.05),as well as a significant increase in Bax protein expression(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,Akt,p-Akt,Bcl2,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax protein expression(P＜0.05).To conclude,Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia,and then inhibit neuronal apoptosis,thus exerting neuroprotective effects and promoting the repair of spinal cord injury.

The 5-hydroxytryptamine 2A receptor (5-HT_2AR) is one of the key targets in the development of novel antidepressants. To develop new antidepressants targeting the 5-HT_2A receptor, this study established a high-throughput screening method for drugs targeting the 5-HT_2A receptor based on the principle of detecting calcium flux signals. The immunofluorescence assay and western blotting were employed to evaluate receptor expression levels in the 5-HT_2AR-CHO cell line. The reaction system parameters, including cell seeding density, DMSO concentration, and dye incubation time, were optimized with Z'-factor and signal window values as evaluation indicators. The specificity, precision, stability, and applicability of the method were assessed. Results indicated that the 5-HT_2AR-CHO cell line stably expressed high levels of the 5-HT_2A receptor. The optimized screening method involved a reaction system with 10 000 cells/well, 0.2% DMSO, and 2 h incubation with Calcium 6 dye. The method demonstrated excellent specificity, with inter-batch precision below 10% for the detection of 5-hydroxytryptamine (5-HT) at low, medium, and high concentrations. Testing four compounds that target the 5-HT_2A receptor- agonists 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD), along with the antagonist MDL100907-yielded Z'-factors (at EC₈₀) greater than 0.85 and signal window values over 0.91. The EC₅₀ values of these compounds were in the nanomolar range, and their potency rank order aligned with previously reported data, confirming the reliability of the established method. When being applied to the detection of 38 known active compounds, the method efficiently identified 5-HT_2A receptor agonists and antagonists while showing no response to non-target compounds. In conclusion, this study successfully constructs a high-throughput screening approach for 5-HT_2A receptor-targeting drugs based on calcium flux signals. The method possesses strong specificity, high sensitivity, and robust stability, being suitable for screening antidepressants targeting the 5-HT_2A receptor.
High-Throughput Screening Assays/methods* ; Receptor, Serotonin, 5-HT2A/metabolism* ; Animals ; CHO Cells ; Cricetulus ; Calcium Signaling/drug effects* ; Antidepressive Agents/pharmacology* ; Humans ; Serotonin 5-HT2 Receptor Antagonists/pharmacology* ; Calcium/metabolism*

Objective To analyze the clinical efficacy and safety of Huoxue Xiaoyi decoction combined with exercise in the treatment of ovarian endometriosis.Methods 36 patients with ovarian endometriosis treated in Guang'anmen Hospital,China Academy of Chinese Medical Sciences from May 2022 to November 2022 were selected and treated with Huoxue Xiaoyi decoction combined with exercise for 3 months.The size of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,female hormones,serum CA125 and CA199,catecholamines and cytokines levels were observed to evaluate the clinical efficacy and safety.Results After treatment,the maximum diameter of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,cytokines(serum IL-1β,IL-2,IL-4,IL-6,IL-8,IL-10)levels were significantly lower than those before treatment(P<0.05).The levels of SHBG and adrenaline were significantly higher than those before treatment(P<0.05).During the treatment,the patient had no adverse drug reactions,vital signs,liver,and kidney function indexes were normal.Conclusion Huoxue Xiaoyi decoction combined with exercise therapy can reduce the size of ovarian ectopic cyst,relieve dysmenorrhea,regulate menstrual volume,increase the level of adrenaline,increase the level of sex hormone binding globulin,reduce the level of cytokines,and has fewer adverse reactions and good safety.

Ulcerative colitis （UC） is a refractory disease of the digestive system characterized by diverse etiologies， complex pathogenesis， a prolonged course， and frequent relapses. In recent years， the incidence of UC has been increasing annually， severely impairing patients' quality of life， posing a risk of malignant transformation that may threaten patients' lives， and resulting in a substantial medical burden. Traditional Chinese medicine （TCM） compound formulas， with their advantages of multi-component and multi-target actions， have become a new therapeutic option for UC. The NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome is a core component of innate immunity， and its aberrant activation is closely associated with the onset and progression of UC， involving multiple processes such as inflammation and oxidative stress， and exhibiting crosstalk with pathways including nuclear factor-κB （NF-κB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and thioredoxin-interacting protein （TXNIP）. At present， NLRP3 has become one of the most intensely studied hotspots in UC-related research. Although increasing studies have focused on the regulation of the NLRP3 inflammasome by TCM compound formulas for UC treatment， challenges remain due to the complex pathogenesis of UC and the compositional diversity of TCM， hindering the realization of precision therapy. In this context， by reviewing literature from the past decade， this paper summarizes the activation process of NLRP3 and its relationship with UC， and elucidates the roles and mechanisms by which TCM compound formulas regulate the NLRP3 inflammasome and related signaling pathways， with a view to providing a reference for further research into the pathogenesis of UC， TCM treatment strategies， and their mechanisms of action.

Ulcerative colitis （UC） is a refractory disease of the digestive system characterized by diverse etiologies， complex pathogenesis， a prolonged course， and frequent relapses. In recent years， the incidence of UC has been increasing annually， severely impairing patients' quality of life， posing a risk of malignant transformation that may threaten patients' lives， and resulting in a substantial medical burden. Traditional Chinese medicine （TCM） compound formulas， with their advantages of multi-component and multi-target actions， have become a new therapeutic option for UC. The NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome is a core component of innate immunity， and its aberrant activation is closely associated with the onset and progression of UC， involving multiple processes such as inflammation and oxidative stress， and exhibiting crosstalk with pathways including nuclear factor-κB （NF-κB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and thioredoxin-interacting protein （TXNIP）. At present， NLRP3 has become one of the most intensely studied hotspots in UC-related research. Although increasing studies have focused on the regulation of the NLRP3 inflammasome by TCM compound formulas for UC treatment， challenges remain due to the complex pathogenesis of UC and the compositional diversity of TCM， hindering the realization of precision therapy. In this context， by reviewing literature from the past decade， this paper summarizes the activation process of NLRP3 and its relationship with UC， and elucidates the roles and mechanisms by which TCM compound formulas regulate the NLRP3 inflammasome and related signaling pathways， with a view to providing a reference for further research into the pathogenesis of UC， TCM treatment strategies， and their mechanisms of action.

Objective To investigate the prevalence status and influencing factors of metabolic syndrome (MS) in adult patients with hypopituitarism (HP) during hospitalization. Methods The data of adult HP patients who received treatment in the hospital were collected from March 2021 to March 2024. The prevalence status of MS in adult HP patients was counted, and logistic regression analysis was adopted to analyze the influencing factors of MS in adult HP patients. Results Among the 308 adult HP patients in this study, 121 cases developed MS and 187 cases did not develop MS, and they were included in the MS group (n=148) and the non-MS group (n=232). The incidence of MS in adult HP patients was 38.95% (148/380). Compared with the non-MS group, the levels of high-density lipoprotein cholesterol, serum total cholesterol and low-density lipoprotein cholesterol in the MS group were higher, the waist circumference was larger, and the growth hormone was lower (P<0.05). After logistic regression analysis, it was found that high-density lipoprotein cholesterol (OR=1.069, 95%CI: 1.010-1.132, P=0.021), total serum cholesterol (OR=1.065, 95%CI: 1.014-1.119, P=0.012), low-density lipoprotein cholesterol (OR=1.055, 95%CI: 1.005-1.108, P=0.031), waist circumference (OR=1.063, 95%CI: 1.006-1.123, P=0.030) and growth hormone (OR=1.077, 95%CI: 1.019-1.138, P=0.009) could independently affect the occurrence of MS in adult HP patients (P<0.05). Conclusion Adult HP patients during hospitalization are often complicated with MS. High-density lipoprotein cholesterol, serum total cholesterol, low-density lipoprotein cholesterol, waist circumference, and growth hormone are factors affecting the occurrence of MS in adult HP patients.

Objective To analyze the clinical efficacy and safety of Huoxue Xiaoyi decoction combined with exercise in the treatment of ovarian endometriosis.Methods 36 patients with ovarian endometriosis treated in Guang'anmen Hospital,China Academy of Chinese Medical Sciences from May 2022 to November 2022 were selected and treated with Huoxue Xiaoyi decoction combined with exercise for 3 months.The size of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,female hormones,serum CA125 and CA199,catecholamines and cytokines levels were observed to evaluate the clinical efficacy and safety.Results After treatment,the maximum diameter of ovarian ectopic cyst,dysmenorrhea VAS score,PBAC score,cytokines(serum IL-1β,IL-2,IL-4,IL-6,IL-8,IL-10)levels were significantly lower than those before treatment(P<0.05).The levels of SHBG and adrenaline were significantly higher than those before treatment(P<0.05).During the treatment,the patient had no adverse drug reactions,vital signs,liver,and kidney function indexes were normal.Conclusion Huoxue Xiaoyi decoction combined with exercise therapy can reduce the size of ovarian ectopic cyst,relieve dysmenorrhea,regulate menstrual volume,increase the level of adrenaline,increase the level of sex hormone binding globulin,reduce the level of cytokines,and has fewer adverse reactions and good safety.

The increasing incidence of myopia has become a significant public health issue worldwide.Since its estab-lishment in 2015,the International Myopia Institute(IMI)has published a series of white papers on myopia prevention and control in 2019 and 2021,advancing the scientific management and clinical research of myopia prevention and control worldwide.In 2023,IMI released new white papers on myopia prevention and control.In this paper,the highlights of the third series of IMI white papers on children,young adults,and emerging research areas in myopia are interpreted,intend-ing to help related professionals understand the management and research focus of myopia patients of different ages.

OBJECTIVE To evaluate the efficacy and safety of Huoxue Xiaoyi Granule in inhibiting the recurrence of endometrio-sis(EMs)after conservative operation,and to provide evidence for Chinese medicine in inhibiting the recurrence of EMs.METHODS A total of 72 patients with qi-stagnation and blood-stasis after EMs operation were selected as the study objects and randomly divid-ed into the Chinese medicine group and the Western medicine group,36 cases in each group.The Chinese medicine group was treated with Huoxue Xiaoyi Granule,and the Western medicine group was treated with GnRH-α.The postoperative recurrence rate,TCM syn-drome score,carbohydrate antigen 125(CA125),dysmenorrhea score,pelvic pain score,pregnancy rate,serum sex hormones[estra-diol(E2),luteinizing hormone(LH),follicle stimulating hormone(FSH)]and safety indexes of the two groups were observed.RE-SULTS At 9 months and 12 months after surgery,the total TCM syndrome scores of the two groups of patients were significantly re-duced(P<0.05),and the Chinese medicine group was better than the Western medicine group(P<0.05);12 months later,the TCM total clinical curative rate in the Chinese medicine group was better than that in the Western medicine group;after surgery,the serum CA125 levels,dysmenorrhea scores and pelvic pain severity of the two groups of patients were significantly reduced(P<0.05,P<0.01);during treatment,the total incidence of adverse reactions in the Chinese medicine group was lower than that in the Western medicine group(P<0.01);the recurrence rate of the Chinese medicine group was slightly lower than that of the Western medicine group,but there was no statistical difference(P>0.05).CONCLUSION Huoxue Xiaoyi Granule can significantly improve TCM syndromes in patients with qi-stagnation and blood-stasis after EMs surgery.It is safe and has equivalent efficacy to GnRH-α in pre-venting postoperative recurrence of EMs,and worthy of clinical promotion and application.

Objective To explore the effect of Huoxue Xiaoyi Formula on ovarian function and pregnancy outcome in endometriosis rats. Methods One hundred female SD rats were fed adaptively for 7 days. According to body weight, 98 rats with a normal estrous cycle were randomly divided into the blank group (n=14), the sham operation group (n=14), the donor group (n=12), and the receptor group (n=58). A rat model of endometriosis was established using allogeneic endometrial transplantation. After the model was successfully established, according to the body weight, 56 rats in the receptor group were randomly divided into the model group, and the Huoxue Xiaoyi Formula low-, medium-, and high-dose groups, with 14 rats in each group. The Huoxue Xiaoyi Formula low-, medium-, and high-dose groups were given 5.86, 11.72, and 23.44 g/kg of Huoxue Xiaoyi Formula, and the blank group, the sham operation group, and the model group were given distilled water by gavage for 15 consecutive days. According to body weight, six rats were randomly selected to take abdominal aortic blood for determination of serum anti-Mullerian hormone (AMH) content by enzyme-linked immunosorbent assay. According to body weight, six rats were randomly selected in the remaining rats to undergo high-frequency small animal ultrasound examination to measure ovarian volume and ovarian artery blood supply (resistance index and pulsatility index), and follicle count were measured. The female mice were fed with male mice at a ratio of 2:1 to observe the pregnancy rate, live fetus number, still fetus number, and absorbed fetus number. The weights of uterus and fetus were measured, while the placental weight, fetal weight, body length, and tail length were measured for live fetus. Bone and visceral malformations were also detected for live fetus. Results There were no significant differences in serum AMH and ovarian volume among the groups. Compared with the model group, the numbers of follicles in the blank group, the sham operation group, and the Huoxue Xiaoyi Formula low-, medium-, and high-dose groups were increased; compared with the Huoxue Xiaoyi Formula low-dose group, the numbers of follicles in the blank group and the Huoxue Xiaoyi Formula medium-dose group were increased (P<0.05). Compared with the model group, the resistance index and pulsatility index of ovarian artery blood flow in the blank group, the sham operation group, and the Huoxue Xiaoyi Formula low-, medium-, and high-dose groups were decreased(P<0.05). There was no significant difference in pregnancy rate among the groups. Compared with the model group and the Huoxue Xiaoyi Formula low-dose group, the live fetus number and the weight of uterus and fetus in the blank group, the sham operation group, and the Huoxue Xiaoyi Formula medium- and high-dose groups were increased (P<0.05). There were no significant differences in the still fetus number, absorbed fetus number, placental weight, fetal weight, body length and tail length among the groups. No visceral or skeletal malformations were found in the live fetal rats among the groups.Conclusion In endometriosis model rats, the ovarian artery blood flow perfusion is insufficient, and the follicle count is reduced, affecting ovary function, thereby reducing the live fetus number. After applying the Huoxue Xiaoyi Formula, it can improve ovarian blood supply, increase the follicle count, and increase the live fetus number. The effect of increasing the live fetus number with the medium- and high-doses of Huoxue Xiaoyi Formula is more significant, and there is no reproductive toxicity.