ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

Objective:To evaluate the role of inositol 1, 4, 5 triphosphate receptor 1 (IP3R1)-regulated changes in mitochondria-associated endoplasmic reticulum membrane (MAM) structure in the long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal mice.Methods:Sixty SPF-grade healthy neonatal C57BL/6J mice of either sex, aged 6 days, weighing 6-10 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), multiple sevoflurane anesthesia group (group S), and IP3R antagonist 2-APB+ multiple sevoflurane anesthesia group (group I+ S). Group S and group I+ S inhaled 3% sevoflurane anesthesia for 2 h starting from 6, 8 and 10 days after birth. In group I+ S, 2-APB 3 mg/kg was intraperitoneally injected before each sevoflurane anesthesia. The open field test was performed at day 31 after birth to assess the spontaneous mobility. The Morris water maze test was performed at days 31-36 after birth to assess the cognitive function. Mice were sacrificed at the end of the water maze test, hippocampal CA1 region was isolated and hippocampal tissues were obtained for determination of the intracellular calcium ion concentration ([Ca 2+ ] i) and rate of necroptosis (using Flow cytometry) and expression of IP3R1, G protein-coupled receptor 75 (GRP75), receptor-interacting protein kinase 1 (RIPK1), RIPK3, and phosphorylated human mixed-series protein kinase-like structural domains (p-MLKL) (by Western blot). Transmission electron microscopy was performed to observe and record the partial length of MAMs, endoplasmic reticulum circumference and mitochondrial circumference. Results:There were no statistically significant differences in the speed, distance, and time of staying at the center in open field tests among the three groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged on postnatal days 33-35, the number of crossing the original platform was reduced, the necroptosis rate in the hippocampal CA1 region and [Ca 2+ ] i were increased, the expression of IP3R, GRP75, RIPK1, RIPK3 and p-MLKL was up-regulated, and the ratio of MAMs partial length/endoplasmic reticulum perimeter and ratio of MAMs partial length/mitochondria perimeter in hippocampal neurons were elevated in group S ( P<0.05). Compared with group S, the escape latency was significantly shortened on postnatal days 32-35, the number of crossing the original platform was increased, the necroptosis rate in the hippocampal CA1 region and [Ca 2+ ] i were decreased, the expression of IP3R, GRP75, RIPK1, RIPK3 and p-MLKL was down-regulated, and the ratio of MAMs partial length/endoplasmic reticulum perimeter and ratio of MAMs partial length/mitochondria perimeter in hippocampal neurons were decreased in group I+ S ( P<0.05). Conclusions:Structural changes in MAMs in the hippocampal CA1 region mediated by the up-regulation of IP3R1 expression are involved in the process of long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal mice.

Objective:To evaluate the role of RhoA/ROCK2 pathway in electroacupuncture (EA) preconditioning-induced reduction of the perioperative neurocognitive disorder (PND) in aged rats.Methods:Eighty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 600-650 g, were divided into 4 groups ( n=20 each) using the random number table method: sham operation group (group S), PND group, EA preconditioning group and EA preconditioning plus RhoA agonist arachidonic acid group (EA+ AA group). The PND model was prepared using exploratory laparotomy performed under 3% sevoflurane anesthesia. In PND, EA and EA+ AA groups, EA preconditioning was initiated 5 days before operation as follows: Bilateral acupoints Zusanli, Hegu and Neiguan were stimulated with sparse-dense waves at 2/15 Hz and an electric current intensity of 1 mA, applied for 30 min a day for 5 consecutive days. Arachidonic acidin 10 mg/kg was intraperitoneally injected at 30 min before surgery in group AA. The open field test was conducted at 3 days postoperatively to measure the autonomous motor function, and the Morris water maze test was conducted at 3-7 days postoperatively to evaluate the cognitive function. After the end of Morris water maze test, the rats were sacrificed, and the hippocampal tissue in CA1 region was obtained for determination of the apoptosis rate of cells and concentrations of cytoplasmic calcium ion ([Ca 2+ ] i) (by flow cytometry) and the expression of phosphorylated RhoA (p-RhoA), ROCK2, and cleaved caspase-3 (by Western blot) and for examination of the ultrastructure of hippocampal neurons (with a transmission electron microscope). Results:There was no statistically significant difference in each parameter of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was marked in PND group. Compared with PND group, the escape latency was significantly shortened, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was significantly attenuated in EA group. Compared with EA group, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was aggravated in EA+ AA group. Conclusions:The mechanism by which EA preconditioning reduces PND is related to inhibiting the activation of hippocampal RhoA/ROCK2 signaling pathway and reducing calcium overload-mediated apoptosis in cells of aged rats.

Post-stroke depression(PSD),a common stroke complication characterized by depressed mood and diminished interest,severely affects patients'recovery and quality of life.Microglial abnormal activation and polarization play key roles in PSD pathogenesis,closely associated with neuroinflammation and imbalance in neu-rotransmitter metabolism.In contrast,traditional Chinese medicine(TCM)demonstrates unique multi-target and multi-level mechanisms:regulating microglial function,ameliorating post-stroke neuroinflammatory environments,and promoting neuroplasticity,thereby potentially alleviating PSD symptoms.This review summarizes TCM's effects on microglial activation/polarization states and its therapeutic advances in PSD,providing novel perspectives and strategies for clinical management.

Objective:To evaluate the role of inositol 1, 4, 5 triphosphate receptor 1 (IP3R1)-regulated changes in mitochondria-associated endoplasmic reticulum membrane (MAM) structure in the long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal mice.Methods:Sixty SPF-grade healthy neonatal C57BL/6J mice of either sex, aged 6 days, weighing 6-10 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), multiple sevoflurane anesthesia group (group S), and IP3R antagonist 2-APB+ multiple sevoflurane anesthesia group (group I+ S). Group S and group I+ S inhaled 3% sevoflurane anesthesia for 2 h starting from 6, 8 and 10 days after birth. In group I+ S, 2-APB 3 mg/kg was intraperitoneally injected before each sevoflurane anesthesia. The open field test was performed at day 31 after birth to assess the spontaneous mobility. The Morris water maze test was performed at days 31-36 after birth to assess the cognitive function. Mice were sacrificed at the end of the water maze test, hippocampal CA1 region was isolated and hippocampal tissues were obtained for determination of the intracellular calcium ion concentration ([Ca 2+ ] i) and rate of necroptosis (using Flow cytometry) and expression of IP3R1, G protein-coupled receptor 75 (GRP75), receptor-interacting protein kinase 1 (RIPK1), RIPK3, and phosphorylated human mixed-series protein kinase-like structural domains (p-MLKL) (by Western blot). Transmission electron microscopy was performed to observe and record the partial length of MAMs, endoplasmic reticulum circumference and mitochondrial circumference. Results:There were no statistically significant differences in the speed, distance, and time of staying at the center in open field tests among the three groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged on postnatal days 33-35, the number of crossing the original platform was reduced, the necroptosis rate in the hippocampal CA1 region and [Ca 2+ ] i were increased, the expression of IP3R, GRP75, RIPK1, RIPK3 and p-MLKL was up-regulated, and the ratio of MAMs partial length/endoplasmic reticulum perimeter and ratio of MAMs partial length/mitochondria perimeter in hippocampal neurons were elevated in group S ( P<0.05). Compared with group S, the escape latency was significantly shortened on postnatal days 32-35, the number of crossing the original platform was increased, the necroptosis rate in the hippocampal CA1 region and [Ca 2+ ] i were decreased, the expression of IP3R, GRP75, RIPK1, RIPK3 and p-MLKL was down-regulated, and the ratio of MAMs partial length/endoplasmic reticulum perimeter and ratio of MAMs partial length/mitochondria perimeter in hippocampal neurons were decreased in group I+ S ( P<0.05). Conclusions:Structural changes in MAMs in the hippocampal CA1 region mediated by the up-regulation of IP3R1 expression are involved in the process of long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal mice.

Objective:To evaluate the role of RhoA/ROCK2 pathway in electroacupuncture (EA) preconditioning-induced reduction of the perioperative neurocognitive disorder (PND) in aged rats.Methods:Eighty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 600-650 g, were divided into 4 groups ( n=20 each) using the random number table method: sham operation group (group S), PND group, EA preconditioning group and EA preconditioning plus RhoA agonist arachidonic acid group (EA+ AA group). The PND model was prepared using exploratory laparotomy performed under 3% sevoflurane anesthesia. In PND, EA and EA+ AA groups, EA preconditioning was initiated 5 days before operation as follows: Bilateral acupoints Zusanli, Hegu and Neiguan were stimulated with sparse-dense waves at 2/15 Hz and an electric current intensity of 1 mA, applied for 30 min a day for 5 consecutive days. Arachidonic acidin 10 mg/kg was intraperitoneally injected at 30 min before surgery in group AA. The open field test was conducted at 3 days postoperatively to measure the autonomous motor function, and the Morris water maze test was conducted at 3-7 days postoperatively to evaluate the cognitive function. After the end of Morris water maze test, the rats were sacrificed, and the hippocampal tissue in CA1 region was obtained for determination of the apoptosis rate of cells and concentrations of cytoplasmic calcium ion ([Ca 2+ ] i) (by flow cytometry) and the expression of phosphorylated RhoA (p-RhoA), ROCK2, and cleaved caspase-3 (by Western blot) and for examination of the ultrastructure of hippocampal neurons (with a transmission electron microscope). Results:There was no statistically significant difference in each parameter of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was marked in PND group. Compared with PND group, the escape latency was significantly shortened, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was significantly attenuated in EA group. Compared with EA group, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptosis rate of hippocampal cells and [Ca 2+ ] i were increased, the expression of p-RhoA, ROCK2 and cleaved-caspase-3 was up-regulated ( P<0.05), and the pathological damage to hippocampal neurons was aggravated in EA+ AA group. Conclusions:The mechanism by which EA preconditioning reduces PND is related to inhibiting the activation of hippocampal RhoA/ROCK2 signaling pathway and reducing calcium overload-mediated apoptosis in cells of aged rats.

Post-stroke depression(PSD),a common stroke complication characterized by depressed mood and diminished interest,severely affects patients'recovery and quality of life.Microglial abnormal activation and polarization play key roles in PSD pathogenesis,closely associated with neuroinflammation and imbalance in neu-rotransmitter metabolism.In contrast,traditional Chinese medicine(TCM)demonstrates unique multi-target and multi-level mechanisms:regulating microglial function,ameliorating post-stroke neuroinflammatory environments,and promoting neuroplasticity,thereby potentially alleviating PSD symptoms.This review summarizes TCM's effects on microglial activation/polarization states and its therapeutic advances in PSD,providing novel perspectives and strategies for clinical management.

Objective To analyze the problems of review of anti-tumor drug prescriptions and medical orders assisted by an information system to improve the review rules,and to provide a reference for improving review quality of anti-tumor drug prescription.Methods The problem with the pre-review of anti-tumor drug prescriptions and medical orders assisted by the information system in Sichuan Cancer Hospital during 2020-2022 were collected.The data came from the MEDICOM PASS system in Sichuan Cancer hospital.Clinical pharmacists made comments on relevant problems and analyzed the results.Results A total of 9 325 antitumor drug pre-approval problems,including 6 279 outpatient prescriptions(67.3%)and 3 046 inpatient orders(32.7%),among which 6 153(66.0%)were unsuitable indications,1 933(20.7%)were drug contraindications,449(4.8%)were problematic routes of administration,345(3.7%)were unsuitable drug compatibility,177(1.9%)were inappropriate drug frequency,133(1.4%)were problematic drug populations,74(0.8%)were unsuitable single doses,39(0.4%)were unacceptable drug interactions,22(0.2%)were unsuitable drug total.The results of clinical pharmacists'comments were 4 459 reasonable cases,with a false positive rate of 47.8%.The false positive problems included 2 264(50.8%)cases of unsuitable indications,1 933(43.3%)cases of drug contraindications,231(5.2%)cases of problematic routes of administration,and 31(0.7%)cases of unsuitable populations.Conclusion The review of anti-tumor drug prescriptions assisted by an information system can effectively intercept irrational drug use and improve the review quality of prescriptions and medical orders.However,the evidence-based medicine date of antitumor drugs is updated quickly.Pharmacists should constantly improve the prescription review rules based on the latest evidence-based medicine data.

Objective To observe the effects of repeated intravitreal injections of ranibizumab and aflibercept on cor-neal morphology of patients with neovascular age-related macular degeneration(nAMD),diabetic macular edema(DME)or retinal vein obstruction(RVO).Methods In this prospective study,64 patients(64 eyes)who underwent therapy in the injection center of the Ophthalmology Department of our hospital from June 2021 to June 2022 were enrolled,including 19 nAMD patients,20 DME patients and 25 RVO patients.Among these patients,29 were treated with aflibercept(40 g·L-1)and 35 were treated with ranibizumab(10 g·L-1).Monocular injections were adopted for all patients,and 3+pro re nata(PRN)therapy was used.Confocal microscope was used for corneal nerve examination,and corneal endo-thelial microscope was used to measure corneal thickness(CT)and corneal endothelial cells.The CT,corneal endothelial cell density(ECD),coefficient of variation(CV),average cell size(ACS),proportion of hexagonal cells(Hex％),cor-neal nerve fiber length(CNFL),corneal nerve fiber density(CNFD)of patients with nAMD,DME and RVO after repeated intravitreal injections of anti-vascular endothelial growth factor(VEGF)drugs were compared,and those parameters at 1 month after injection of different anti-VEGF drugs were compared with the baseline.Results Before injection,ECD in the DME group was lower than that in the nAMD and RVO groups,and the ACS in the DME group was higher than that in the nAMD and RVO groups(all P＜0.05).There was no significant difference in the other indexes among the three groups(all P＞0.05).After 3 injections of anti-VEGF drugs,the ECD in the DME group was lower than that in the nAMD and RVO groups,the ACS in the DME group was higher than that in the nAMD and RVO groups,and the CNFL in the DME group was lower than that in the nAMD and RVO groups(all P＜0.05).The ECD decreased compared with that before injection from the 2nd injection of aflibercept in the nAMD group(all P＜0.05).Hex％decreased significantly after each injection compared with the baseline(all P＜0.05).Other indexes have no significant differences from the baseline(all P＞0.05).In the RVO group,ECD decreased from the 2nd ranibizumab injection compared with the baseline(all P＜0.05).Conclu-sion Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex％and ECD to a certain extent.After injec-tions,CNFL in the DME group is significantly lower than that in the nAMD and RVO groups.