1.Progress in the application of poloxamer in new preparation technology
Xue QI ; Yi CHENG ; Nan LIU ; Zengming WANG ; Hui ZHANG ; Aiping ZHENG ; Dongzhou KANG
China Pharmacy 2025;36(5):630-635
Poloxamer, as a non-ionic surfactant, exhibits a unique triblock [polyethylene oxide-poly (propylene oxide)-polyethylene oxide] structure, which endows it with broad application potential in various fields, including solid dispersion technology, nanotechnology, gel technology, biologics, gene engineering and 3D printing. As a carrier, it enhances the solubility and bioavailability of poorly soluble drugs. In the field of nanotechnology, it serves as a stabilizer etc., enriching preparation methods. In gel technology, its self-assembly behavior and thermosensitive properties facilitate controlled drug release. In biologics, it improves targeting efficiency and reduces side effects. In gene engineering, it enhances delivery efficiency and expression levels. In 3D printing, it provides novel strategies for precise drug release control and the production of high-quality biological products. As a versatile material, poloxamer holds promising prospects in the pharmaceutical field.
2.Construction of quality control evaluation indicators for common diseases surveillance among students
CUI Mengjie, MENG La, MA Qi, XING Yi
Chinese Journal of School Health 2025;46(6):894-898
Objective:
To construct a quality control evaluation indicator system for the surveillance of common diseases among students, so as to provide a reference for the quality control of surveillance projects.
Methods:
Based on literature review and expert interviews, a preliminary framework and candidate indicators were developed from June to August in 2024. Twenty domain experts participated in two rounds of Delphi consultations conducted via email, providing importance ratings, judgment basis, familiarity levels, and feasibility assessments for each indicator. And a quality control evaluation indicator system for the surveillance of common diseases among students was ultimately constructed.
Results:
The consulted experts aged 33-53, with an average age of (45.25±5.03) years, were from government health administration departments( n =1), centers for disease control and prevention at different levels( n =16), academic and research institutions( n =3). Their work experience in school health related fields ranged from 6 to 33 years, with an average of (16.70±8.25) years. The activeness of experts in both rounds of consultation was 100%, the mean expert authority coefficient was 0.90, and the mean feasibility evaluation was 0.75. Kendall s W test showed that the expert coordination coefficient for the first round was 0.26, and for the second round, it was 0.33 ( P <0.01). After two rounds of expert consultation, a set of quality control evaluation indicators for the surveillance of common diseases among students was ultimately constructed, including 6 first level indicators, 19 second level indicators, and 37 third level indicators.
Conclusion
The scientifically developed evaluation indicator system facilitates high quality implementation of student common disease surveillance programs.
3.Clinical features of anti-leucine rich glioma inactivated 1 antibody autoimmune encephalitis
Yongfang LI ; Yi TANG ; Qi QIN
Journal of Apoplexy and Nervous Diseases 2025;42(6):512-516
Objective To investigate the clinical manifestations and prognosis of patients with anti-leucine rich glioma inactivated 1(LGI1)antibody encephalitis. Methods A retrospective analysis was performed for the data of patients with anti-LGI1 antibody encephalitis who were hospitalized in Department of Neurology,Xuanwu Hospital,Capital Medical University,from September 2019 to December 2023,including clinical features,treatment,and prognosis. Results A total of 80 patients were enrolled,including 48 male patients and 32 female patients. Of all 80 patients,51(63.8%)had the initial symptom of epilepsy,13(16.3%)had the initial symptom of faciobrachial dystonic seizures,26(32.5%)had the initial symptom of cognitive impairment,and 12(15%)had the initial symptom of mental and behavioral disorders. As for comorbidities,there were 28 patients(35%)with hyponatremia,22(27.5%)with Hashimoto's thyroiditis,and 5(6.25%)with tumor. All 80 patients tested positive for serum LGI1 antibody,and 69(86.3%)tested positive for LGI1 antibody in cerebrospinal fluid. Among the 80 patients,37(46.25%)had abnormalities on magnetic resonance imaging,and 30 had abnormalities on 18F-FDG PET/CT. There were 50 patients with abnormalities on video electroencephalography. A total of 77 patients received first-line immunotherapy,and after follow-up for 1 year,19.4% of the patients had the sequela of seizure,59.7% of the patients had deterioration of the memory,and 48.6% of the patients had mental and behavioral disorders. Conclusion Epilepsy,cognitive impairment,and mental and behavior disorders are the most common manifestations of anti-LGI1 antibody encephalitis. There is generally a good prognosis after immunotherapy,with the sequelae of cognitive impairment and mental and behavioral disorders.
4.Effects of Non-invasive Light Flicker on Functional Properties of Primary Visual Cortex in Adult Mice
Xue-Qi LI ; Yi-Feng ZHOU ; Guang-Wei XU
Progress in Biochemistry and Biophysics 2025;52(9):2360-2375
ObjectiveAs the central hub of the classical visual pathway, the primary visual cortex not only encodes and processes visual information but also establishes dense neural circuit connections with higher-order cognitive brain regions. Numerous studies have shown that 40 Hz flicker stimulation can induce γ oscillations in the brain and significantly improve learning and cognitive impairments in patients with neurodegenerative diseases. Moreover, flickering light phenomena naturally occur in daily environments. Given that the primary visual cortex serves as the brain’s first cortical hub for receiving visual input, it is essential to comprehensively understand how non-invasive light flicker stimulation modulates its information processing mechanisms. This study systematically investigates the effects of non-invasive light flicker stimulation at different frequencies on the functional properties of neurons in the primary visual cortex of adult mice, aiming to uncover how such stimulation modulates this region and, consequently, affects overall brain function. MethodsThree groups of adult mice (approximately 12 weeks old) were exposed to light flicker stimulation at frequencies of 20 Hz, 40 Hz, and 60 Hz, respectively, for a duration of two months. A control group was exposed to the same light intensity without flickering. Following the stimulation period, in vivo multi-channel electrophysiological recordings were conducted. During these recordings, anesthetized mice were presented with various types of moving sinusoidal light gratings to assess the effects of different flicker frequencies on the functional properties of neurons in the primary visual cortex. ResultsThe experimental results demonstrate that two months of light flicker stimulation at 20 Hz, 40 Hz, and 60 Hz enhances the orientation tuning capabilities of neurons in the primary visual cortex. Specifically, 40 Hz and 60 Hz stimulation improved contrast sensitivity, whereas 20 Hz had no significant effect. Further analysis revealed that all three frequencies reduced neuronal response variability (as measured by the Fano factor), increased the signal-to-noise ratio, and decreased noise correlation (rsc) between neurons. ConclusionNon-invasive light flicker stimulation enhances orientation tuning (e.g., orientation bias index) and contrast sensitivity (e.g., contrast threshold and C50) in neurons of the primary visual cortex. This enhancement is likely due to improved information processing efficiency, characterized by reduced neuronal variability and increased signal-to-noise ratio. These findings suggest that the primary visual cortex can achieve precise and efficient information encoding in complex lighting environments by selectively adapting to different flicker frequencies and optimizing receptive field properties. This study provides new experimental evidence on how various types of light flicker influence visual perception and offers insights into the mechanisms through which specific frequencies enhance brain function.
5.Effect of Stasis-dispelling and Detoxifying Therapy on Clinical Efficacy and JNK Signaling Pathway-related Protein Expression in Endometriosis Patients with Syndrome of Kidney Deficiency and Blood Stasis
Tingting WANG ; Zhaokang QI ; Jinxin REN ; Shuai ZHAO ; Chunxiao WEI ; Yi YU ; Fang LIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):120-129
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.
6.Effect of Stasis-dispelling and Detoxifying Therapy on Clinical Efficacy and JNK Signaling Pathway-related Protein Expression in Endometriosis Patients with Syndrome of Kidney Deficiency and Blood Stasis
Tingting WANG ; Zhaokang QI ; Jinxin REN ; Shuai ZHAO ; Chunxiao WEI ; Yi YU ; Fang LIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):120-129
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.
7.Ameliorative effect of patchouli alcohol on mice with lung-heat syndrome based on PI3K/Akt/NF-κB pathway
Linze LI ; Yi LI ; Haoyi QIAO ; Jiakang JIAO ; Qi ZHANG ; Xiaofang WU ; Xingyu ZHAO ; Yinming ZHAO ; Chun WANG ; Jianjun ZHANG ; Linyuan WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):459-470
Objective:
To investigate the therapeutic effect of patchouli alcohol on mice with lung-heat syndrome based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/nuclear factor-kappa B(NF-κB) signaling pathway.
Methods:
First, network pharmacology was used to predict the potential targets of patchouli alcohol in the treatment of lung-heat syndrome, and a "component-disease-key target" network was constructed for pathway analysis. Then, 40 BALB/c mice were assigned to the normal, lung-heat model, honeysuckle, and low-dose and high-dose patchouli alcohol groups. All groups, except the blank group, were intranasally infected with 50 μL (103 TCID50) of influenza virus solution. After two hours of infection, mice were treated once a day for seven consecutive days. The therapeutic mechanism of patchouli alcohol was explored by measuring pulmonary inflammatory factors, the PI3K/Akt/NF-κB pathway, hypothalamic fever markers (PGE2, cAMP, cGMP levels), rectal temperature, and tissue energy metabolism.
Results:
Network pharmacology identified 135 target genes related to patchouli alcohol and lung-heat syndrome, with the key targets being STAT3, H1F1A, and NF-κB1. In animal experiments, patchouli alcohol significantly alleviated influenza virus-induced lung inflammatory damage in mice with lung-heat syndrome, inhibited the expression of TNF-α and IL-6 in lung tissues(P<0.01), and suppressed the activation of the PI3K/Akt/NF-κB pathway. It also reduced hypothalamic levels of PGE2 and cAMP(P<0.01), suppressed the increase in rectal temperature, significantly decreased liver glycogen and pyruvate levels(P<0.01), and increased the activities of SDH, LDH, and Na+ -K+ -ATPase in the liver(P<0.01)
Conclusion
Patchouli alcohol improves the symptoms of lung-heat syndrome in mice by inhibiting the activation of the PI3K/Akt/NF-κB pathway, reducing proinflammatory cytokines and inflammatory damage, and regulating hypothalamic fever markers and energy metabolism.
8.Study on the effects of carvacrol on stomach-heat and stomach-cold rats and its mechanism of cooling and clearing based on energy metabolism and gastrointestinal function
Qi ZHANG ; Yi LI ; Hongye LI ; Fengwei ZHANG ; Minghui JIANG ; Xingyu ZHAO ; Linze LI ; Xiaofang WU ; Yinming ZHAO ; Songrui DI ; Jianjun ZHANG ; Chun WANG ; Linyuan WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):471-482
Objective:
To investigate the biological effects of carvacrol on rats with stomach-heat and stomach-cold and its regulation on transient receptor potential(TRP) channels in rats with stomach-heat, and to study the cold and heat properties of carvacrol and its possible mechanism.
Methods:
According to the random number method, 100 SD rats were divided into stomach-heat blank group, stomach-heat model group, Coptidis Rhizoma group, stomach-heat low-dose and high-dose carvacrol group, stomach-cold blank group, stomach-cold model group, Baked ginger group, stomach-cold low-dose group and high-dose carvacrol group, 10 rats in each group. The rat model of stomach-heat was established by intragastric administration of pepper aqueous solution (0.80 g/kg) and anhydrous ethanol, and the rat model of stomach-cold was established by intragastric administration of water extract of Anemarrhena asphodeloides and sodium hydroxide (10.40 g/kg). On the day of modeling, the rats in the Baked ginger group were given Baked ginger decoction (0.78 g/kg), and the rats in the Coptidis Rhizoma group were given Coptidis Rhizoma decoction (0.43 g/kg).The stomach-cold and stomach-heat low-dose group of carvacrol was given carvacrol emulsion (40 mg/kg), high-dose group was given carvacrol emulsion (80 mg/kg).All rats of the blank and model groups were given the equal volume of emulsion prepared by 5% dimethyl sulfoxide, 1% Tween 80, 1% polyethylene glycol 400, and 93% normal saline, once a day, for 7 days. The general condition of rats was observed and the body mass was recorded. The pathological morphology of gastric tissue was observed by hematoxylin-eosin staining. The changes of material and energy metabolism, cyclic nucleotide (cAMP), thyroid hormone and gastrointestinal hormone in each group were determined by enzyme-linked immunosorbent assay. The expression levels of transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential channel M8 (TRPM8) and uncoupling protein-1 (UCP1) in rats with gastric fever were detected by Western blotting.
Results:
Compared with the stomach-heat blank group, the body mass of rats in the stomach-heat model group decreased at the fifth and seventh day (P<0.05). The contents (or ratio) of hepatic glycogen (HGlyc), total cholesterol (TC), triglyceride (TG), and vasoactive intestinal peptide (VIP) were decreased (P<0.05), and Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, cytochrome C oxidase (COX), NADH dehydrogenase (ND), cyclic adenosine phosphate (cAMP), cAMP/cyclic guanosine phosphate (cGMP), triiodothyronine (T3), thyroxine (T4), gastrin (GAS), motilin (MTL), and α-amylase (α-AMS) all increased (P<0.05). Compared with the stomach-heat model group, the body mass of rats in the Coptidis Rhizoma group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, VIP and α-AMS were increased, and Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and GAS all decreased (P<0.05). The body mass of rats in the stomach-heat low-dose carvacrol group decreased at the seventh day. The contents (or ratio) of HGlyc, TC, and VIP were increased, Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and MTL all decreased, the expression of TRPV1 and UCP1 in gastric tissue decreased, while TRPM8 increased (P<0.05) in rats of the stomach-heat low-dose and high-dose carvacrol groups. Compared with the stomach-cold blank group, the body mass of rats in the stomach-cold model group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, α-AMS, and VIP all increased, while Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, GAS, and MTL all decreased (P<0.05). Compared with the stomach-cold model group, the body mass of rats in the Baked ginger group was increased at the seventh day, and the contents (or ratio) of HGlyc, VIP, and α-AMS all decreased, while Na+ -K+ -ATPase, COX, ND, cAMP/cGMP, T3, T4, GAS, and MTL all increased (P<0.05). The contents of HGlyc, cAMP, α-AMS, and VIP of rats in the stomach-cold low and high-dose carvacrol group all decreased (P<0.05). TG in the stomach-cold low-dose carvacrol group was increased. TC, Ca2+ -Mg2+ -ATPase, and cGMP all increased, while cAMP/cGMP decreased (P<0.05) in the high-dose carvacrol group.
Conclusion
In this study, the rat model of stomach-cold and stomach-heat were successfully established by using cold and heat factors. The result showed that carvacrol had a certain inhibitory effect on body mass, material energy metabolism, cyclic nucleotide level, thyroid hormone and gastrointestinal function in rats with stomach-heat, indicating that the drug was cold. Carvacrol′s cold medicinal property could be biologically explained by TRPV1 activation, UCP1 induction, and TRPM8 suppression.
9.DIA Proteomics Reveals Mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis Extract in Treating α-Syn Transgenic Parkinson's Disease in Mice
Qi ZHENG ; Yi LU ; Donghua YU ; Liangyou ZHAO ; Chunsheng LIN ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):40-50
ObjectiveTo investigate the mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis extract (ASH) in treating Parkinson's disease (PD) in mice by Data-Independent Acquisition (DIA) proteomics. MethodsThe α-Synuclein (α-Syn) transgenic PD mice were selected as suitable models for PD, and they were randomly assigned into PD, ASH (61.25 mg·kg-1), and Madopar (97.5 mg·kg-1) groups. Male C57BL/6 mice of the same age were selected as the control group, with eight mice in each group. Mice were administrated with corresponding drugs by gavage once a day for 20 days. The pole climbing time and the number of autonomic activities were recorded to evaluate the exercise ability of mice. Hematoxylin-eosin staining was employed to observe neuronal changes in the substantia nigra of PD mice. Immunohistochemistry (IHC) was employed to measure the tyrosine hydroxylase (TH) activity in the substantia nigra and assess the areal density of α-Syn in the striatum. DIA proteomics was used to compare protein expression in the substantia nigra between groups. IHC was utilized to validate key differentially expressed proteins, including Lactotransferrin, Notch2, Ndrg2, and TMEM 166. The cell counting kit-8 (CCK-8) method was used to investigate the effect of ASH on the viability of PD cells with overexpression of α-Syn. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the protein and mRNA levels of Lactotransferrin, Notch2, Ndrg2, and TMEM 166 in PD cells. ResultsCompared with the control group, the model group showed prolonged pole climbing time, diminished coordination ability, reduced autonomic activities (P<0.01), and reduced swelling neurons. Compared with the model group, ASH and Madopar reduced the climbing time, increased autonomic activities (P<0.01), and ameliorated neuronal damage. Compared with the control group, the model group showed a decrease in TH activity in the substantia nigra and an increase in α-Syn accumulation in the striatum (P<0.01). Compared with the model group, the ASH group showed an increase in TH activity and a reduction in α-Syn accumulation (P<0.05). DIA proteomics revealed a total of 464 differentially expressed proteins in the model group compared with the control group, with 323 proteins being up-regulated and 141 down-regulated. A total of 262 differentially expressed proteins were screened in the ASH group compared with the model group, including 85 proteins being up-regulated and 177 down-regulated. Kyoto encylopedia of genes and genomes (KEGG) pathway analysis indicated that ASH primarily regulated the Notch signaling pathway. The model group showed up-regulation in protein levels of Notch2, Ndrg2, and TMEM 166 and down-regulation in the protein level of Lactotransferrin compared with the control group (P<0.01). Compared with the model group, ASH down-regulated the protein levels of Notch2, Ndrg2, and TMEM 166 (P<0.05) while up-regulating the protein level of Lactotransferrin (P<0.01). The IHC results corroborated the proteomics findings. The cell experiment results showed that compared with the control group, the modeling up-regulated the mRNA and protein levels of Notch2, Ndrg2, and TMEM 166 (P<0.01), while down-regulating the mRNA and protein levels of Lactotransferrin (P<0.01). Compared with the model group, ASH reduced the mRNA and protein levels of Notch2, Ndrg2, and TMEM 166 (P<0.01), while increasing the mRNA and protein levels of Lactotransferrin (P<0.05, P<0.01). ConclusionASH may Synergistically inhibit the Notch signaling pathway and mitigate neuronal damage by down-regulating the expression of Notch2 and Ndrg2. Additionally, by up-regulating the expression of Lactotransferrin and down-regulating the expression of TMEM166, ASH can address brain iron accumulation, intervene in ferroptosis, inhibit mitophagy, and mitigate reactive oxygen species damage, thereby protecting nerve cells and contributing to the treatment of PD.
10.Clinical study on the treatment of chronic atrophic gastritis with spleen and stomach weakness syndrome by Piwei Peiyuan Pill combined with moxibustion
Kairui WU ; Yu YE ; Bei PEI ; Biao SONG ; Yi ZHANG ; Tingting LI ; Qi YANG ; Yun LIU ; Xuejun LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):280-290
Objective:
To determine the clinical efficacy and mechanism of Piwei Peiyuan Pill (PPP) combined with moxibustion for treating patients with chronic atrophic gastritis (CAG) with spleen and stomach weakness syndrome.
Methods:
Ninety-six CAG patients with spleen and stomach weakness syndrome who met the inclusion and exclusion criteria were enrolled at the Department of Spleen and Stomach Diseases of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to December 2023. The patients were randomly divided into a control, a Chinese medicine, and a combined group using a random number table method, with 32 cases in each group (two cases per group were excluded). The control group was treated with rabeprazole combined with folic acid tablets (both thrice daily), the Chinese medicine group was treated with PPP (8 g, thrice daily), and the combined group was treated with moxa stick moxibustion (once daily) on the basis of the Chinese medicine group for 12 consecutive weeks. Gastric mucosa atrophy in the three groups was observed before and after treatment. The gastric mucosal pathological score was evaluated. The Patient Reported Outcome (PRO) scale was used to evaluate the patients′ physical and mental health status and quality of life.An enzyme-linked immunosorbent assay was used to detect serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-10, IL-37, and transforming growth factor (TGF)-β levels in each group. Real-time fluorescence PCR was used to detect the relative expression levels of signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) mRNA in each group. Western blotting was used to detect the relative expression levels of proteins related to the STAT3/mTOR signaling pathway, and the adverse drug reactions and events were recorded and compared.
Results:
There was no statistical difference in age, gender, disease duration, family history of gastrointestinal tumors, alcohol consumption history, and body mass index among the three groups of patients.The total therapeutic efficacy rates of the control, Chinese medicine, and combined groups in treating gastric mucosal atrophy were 66.67% (20/30), 86.67% (26/30), and 90.00% (27/30), respectively (P<0.05). Compared to before treatment, the pathological and PRO scale scores of gastric mucosa in each group decreased after treatment, and TNF-α, IL-1β, IL-37, and TGF-β levels decreased. The relative STAT3 and mTOR mRNA expression levels, as well as the relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels decreased (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the control group, the pathological score of gastric mucosa, PRO scale score, TNF-α, IL-1β, IL-37, TGF-β content, relative STAT3 and mTOR mRNA expression levels, and relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels in the Chinese medicine and combined groups after treatment were reduced (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the Chinese medicine group, the combined group showed a decrease in relative STAT3, mTOR mRNA expression levels, and STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels (P<0.05).
Conclusion
The combination of PPP and moxibustion may regulate the inflammatory mechanism of the body by inhibiting the abnormal activation of the STAT3/mTOR signaling pathway, upregulating related anti-inflammatory factor levels, downregulating pro-inflammatory factor expression, and increasing related repair factor expression, thereby promoting the recovery of atrophic gastric mucosa, reducing discomfort symptoms, and improving the physical and mental state of CAG patients with spleen and stomach weakness syndrome.


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