1.Photodynamic performance and anti-lung cancer effect of novel chlorin compounds
Yan QIU ; Hao WU ; Yafen DONG ; Ye CHEN ; Jian WANG ; Hui JIN
Journal of Pharmaceutical Practice and Service 2026;44(1):39-45
Objective To study the photodynamic performance and the killing effect of photodynamic therapy on lung cancer of novel chlorin compounds 2-(4-(5,15,20-triphenyl-7H,8H-porphyrin-10-yl) phenoxy) acetic acid(D1)and 4-(4-(5,15,20-triphenyl-7H,8H-porphyrin-10-yl) phenoxy) butanoic acid (D2). Methods The ultraviolet visible absorption spectrum and fluorescence spectrum of D1 and D2 were determined. The singlet oxygen generation capacity of D1 and D2 was measured by using DPBF as singlet oxygen capture agent. Fluorescence assay was used to detect the cellular phagocytosis rate of the compounds in A549 cells, and MTT assay was used to detect their dark toxicity and phototoxicity. A nude mouse model of lung cancer was established to investigate the antitumor activity of the compounds mediated photodynamic action in vivo, and the blood concentration of D2 in nude mice, its distribution in tumor tissue and skin tissue were further detected. Results D1 and D2 had strong absorption at 652 nm with the best excitation wavelength at 429 nm and 427 nm, and the optimal emission wavelength was at about 659 nm. They also had a higher singlet oxygen generation rate than the control drug m-THPC. D1 and D2 had no dark toxicity at concentrations below 10 μmol/L, and could be ingested by A549 cells, basically reaching saturation in 18~24 hours. After laser irradiation at 650 nm wavelength, D1 and D2 showed significant antitumor activity in vivo and in vitro (P<0.01). However, D2 could selectively accumulate in tumor tissues after administration, and the optimal treatment time was less than 30 min after administration. Conclusion D2 had excellent photodynamic antitumor activity and could selectively aggregate in tumor tissues, which had the potential to be a candidate drug for photosensitizer and treatment of lung cancer with independent intellectual property rights, and was worth further research.
2.Combined Therapy of Traditional Chinese and Western Medicine for Hepatitis B Virus Infection: A Review
Xuan WU ; Hui LI ; Jian HUANG ; Xikun YANG ; Yan ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):279-288
Hepatitis B virus (HBV) infection is the primary cause of viral hepatitis and represents a substantial disease burden in China. However, effective and safe agents capable of completely eliminating HBV DNA are still lacking. In modern medicine, anti-HBV strategies mainly target covalently closed circular DNA (cccDNA), among other mechanisms, and multiple novel drugs are currently under clinical investigation. Traditional medicine has been shown to exert anti-HBV effects through direct pathways, such as blocking viral entry, as well as indirect pathways, including the regulation of programmed cell death. Studies have confirmed that the integration of traditional Chinese medicine (TCM) and Western medicine in treating HBV infection and its related complications offers complementary advantages, particularly in enhancing HBV clearance rates, improving liver function, preventing various complications, and delaying the progression from hepatic fibrosis to hepatocellular carcinoma. This review focuses on advances in anti-HBV research involving TCM, Western medicine, and their integrated application, aiming to provide a basis for integrated HBV therapy and new drug development.
3.Shaoyaotang Regulates miRNA-155-mediated SOCS1/JAK1/STAT1 Signaling Pathway to Affect Macrophage Polarization
Qi CHENG ; Bo ZOU ; Youwei XIAO ; Yiqian YU ; Ruoru HUANG ; Yan GONG ; Jiachun XIONG ; Jun XIONG ; Dichang LAI ; Dongsheng WU ; Hui CAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):43-52
ObjectiveTo investigate the mechanism by which Shaoyaotang regulates the miRNA-155-mediated suppressor of cytokine signaling 1 (SOCS1)/Janus kinase 1 (JAK1)/signal transducer and activator of transcription 1 (STAT1) signaling pathway and thereby affects macrophage polarization. MethodsThe cell-counting kit-8 (CCK-8) assay was used to detect the effect of drug-containing serum of Shaoyaotang at different concentrations on the viability of RAW 264.7 cells. A cell model of inflammation was established by stimulating RAW264.7 cells with lipopolysaccharide (LPS) at a concentration of 10 mg·L-1 The modeled cells were assigned by the random number table method into seven groups: LPS-induced M1 polarization (model), M1+miRNA-155 mimics, M1+miRNA-155 inhibitor, M1+Shaoyaotang-containing serum, M1+miRNA-155 mimics+Shaoyaotang-containing serum, M1+miRNA-155 inhibitor+Shaoyaotang-containing serum, and M1+blank serum. Enzyme-linked immunosorbent assay was employed to measure the levels of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)]. Immunofluorescence assay was used to detect the expression of macrophage polarization markers [inducible nitric oxide synthase (iNOS) and macrophage mannose receptor 1 (CD206)]. Real-time PCR was employed to measure the expression of miRNA-155 in cells. Western blot was performed to determine the protein levels of SOCS1, STAT1, and JAK1. ResultsCompared with the LPS-induced M1 polarization (model) group, the M1+miRNA-155 mimics group showed up-regulated expression of miRNA-155, JAK1, STAT1, TNF-α, IL-6, IL-1β, and iNOS (P<0.05) and down-regulated expression of CD206 (P<0.05). In both the M1+miRNA-155 inhibitor group and the M1+Shaoyaotang-containing serum group, the expression levels of miRNA-155, JAK1, STAT1, TNF-α, IL-6, IL-1β, and iNOS were down-regulated (P<0.05), while those of SOCS1 and CD206 were up-regulated (P<0.05). Compared with the M1+miRNA-155 mimics group, the M1+miRNA-155 mimics+Shaoyaotang-containing serum group showed down-regulated expression of miRNA-155, JAK1, STAT1, TNF-α, IL-6, IL-1β, and iNOS (P<0.05) and up-regulated expression of SOCS1 and CD206 (P<0.05). Compared with the M1+miRNA-155 inhibitor group, the M1+miRNA-155 inhibitor+Shaoyaotang-containing serum group showed down-regulated expression of miRNA-155, JAK1, STAT1, TNF-α, IL-6, IL-1β, and iNOS (P<0.05) and up-regulated expression of SOCS1 and CD206 (P<0.05). ConclusionShaoyaotang regulates macrophage polarization by modulating miRNA-155 expression and interfering with the SOCS1/JAK1/STAT1 signaling pathway. The findings provide new experimental evidence for the treatment of ulcerative colitis with Shaoyaotang.
4.Effect and Mechanisms of Shaoyaotang on Murine Ulcerative Colitis via Modulating Macrophage Glycolytic Reprogramming and Polarization Through HIF-1α Pathway
Yiqian YU ; Hui CAO ; Dongsheng WU ; Bo ZOU ; Ruoru HUANG ; Qi CHENG ; Youwei XIAO ; Yan GONG ; Jiachun XIONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):53-60
ObjectiveTo investigate the potential role and underlying mechanisms of Shaoyaotang in intervening macrophage glycolytic reprogramming in ulcerative colitis (UC). MethodsForty-eight C57BL/6 mice were randomly divided into six groups: Normal control group, model group, mesalazine group (0.39 g·kg-1), Shaoyaotang group (15.54 g·kg-1), 2-deoxy-D-glucose (2-DG) group (glycolysis inhibitor, 100 mg·kg-1), and 2-DG + Shaoyaotang combined group (100 mg·kg-1+15.54 g·kg-1). Except for the normal control group, mice in the other five groups were induced to establish UC models using dextran sulfate sodium (DSS). The normal control group was administered pure water via intragastric gavage, while the other groups received intragastric gavage of mesalazine solution, intragastric gavage of Shaoyaotang, and the 2-DG group was treated with 2-DG via intraperitoneal injection. After 7 consecutive days of treatment, colonic tissues were extracted. Hematoxylin and eosin (HE) staining was performed to evaluate histopathological changes and tissue injury in the colon. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) in colonic tissues. Western blot analysis was employed to determine the expression levels of hypoxia-inducible factor-1α (HIF-1α), glucose transporter (GLUT1), lactate dehydrogenase A (LDHA), pyruvate kinase M2 (PKM2), and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in colonic tissues. Immunofluorescence was conducted to detect the expression of CD206 and inducible nitric oxide synthase (iNOS) in colonic tissues. Liquid chromatography-mass spectrometry (LC-MS) was utilized to measure lactate and citrate levels in colonic tissues. ResultsCompared with the normal control group, mice in the model group exhibited a significant increase in disease activity index (DAI) scores, accompanied by colonic mucosal congestion, edema, and inflammatory cell infiltration, significantly elevated expression of the inflammatory cytokine TNF-α (P<0.05), significantly decreased IL-10 expression (P<0.05), significantly increased levels of HIF-1α, GLUT1, LDHA, PKM2, and PFKFB3 in colonic tissues (P<0.05), markedly elevated iNOS expression (P<0.05), significantly decreased CD206 expression (P<0.05), and significantly elevated lactate and citrate levels in colonic tissues (P<0.05). In contrast to the model group, the Shaoyaotang group, inhibitor group, and Shaoyaotang combined with inhibitor group demonstrated amelioration of mucosal injury in colonic tissues, markely decreased expression levels of the inflammatory cytokine TNF-α (P<0.05), elevated IL-10 expression levels, significantly decreased expression of HIF-1α, GLUT1, LDHA, PKM2, and PFKFB3 (P<0.05), markedly reduced iNOS expression levels (P<0.05), significantly increased CD206 expression (P<0.05) and significantly decreased lactate and citrate levels (P<0.05). ConclusionShaoyaotang ameliorates symptoms of DSS-induced UC in mice, and its therapeutic mechanism may be associated with regulating macrophage glycolytic reprogramming via modulation of the HIF-1α signaling pathway.
5.Shaoyaotang Ameliorates Ulcerative Colitis by Regulating miR-155-5p
Ruoru HUANG ; Bo ZOU ; Yu ZHANG ; Yiqian YU ; Qi CHENG ; Youwei XIAO ; Jiachun XIONG ; Yan GONG ; Dongshen WU ; Hui CAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):61-68
ObjectiveTo investigate the role of microRNA-155-5p (miR-155-5p) in ulcerative colitis (UC) and study the molecular mechanism of Shaoyaotang in the treatment of UC by regulating miR-155-5p. MethodsForty-eight SPF-grade male C57BL/6 mice were selected and assigned via the random number table method into 6 groups (n=8): A blank control group, a model group, a mesalazine (0.39 g·kg-1) group, a Shaoyaotang (31.08 g·kg-1) group, a Janus kinase 1 (JAK1) inhibitor (baricitinib, 10 mg·kg-1) group, and a Shaoyaotang combined with inhibitor (baricitinib 10 mg·kg-1 + Shaoyaotang 31.08 g·kg-1) group. After successful modeling of UC by gavage of 3% dextran sulphate sodium solution, each group received corresponding drug intervention for 7 days. Shaoyaotang and mesalazine were administered by gavage, and baricitinib by intraperitoneal injection. Twenty-four hours after the last administration, mice were anesthetized by intraperitoneal injection of pentobarbital sodium, and blood was collected for determination of white blood cell count and erythrocyte sedimentation rate (ESR). Mice were then sacrificed for measurement of colon length. Hematoxylin-eosin staining was used to observe colonic pathological changes and perform pathological scoring. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to determine the relative expression of miR-155-5p in the colonic tissue, and Western blot was used to determine the protein levels of JAK1, phosphorylated JAK1 (p-JAK1), suppressor of cytokine signaling 1 (SOCS1), signal transducer and activator of transcription 1 (STAT1), and phosphorylated STAT1 (p-STAT1). ResultsCompared with the blank control group, the model group showed increased disease activity index (DAI) score and pathological score, shortened colon, upregulated relative expression of miR-155-5p and protein levels of p-JAK1 and p-STAT1, downregulated protein level of SOCS1 in the colonic tissue, prolonged time of erythrocyte sedimentation, and increased white blood cell count (P<0.01). Compared with the model group, all drug-treated groups exhibited improvements in the above indicators (P<0.01). Moreover, the Shaoyaotang group showed better therapeutic effects than the mesalazine group in regulating miR-155-5p expression, related protein levels, DAI score, and colonic pathological score (P<0.01). ConclusionShaoyaotang may downregulate miR-155-5p to relieve its inhibition on SOCS1, thereby suppressing the excessive activation of the JAK1/STAT1 signaling pathway and ultimately alleviating intestinal inflammatory damage.
6.Shaoyaotang Regulates TLR4/MyD88/NF-κB Signaling Pathway to Protect Intestinal Mucosal Barrier in Ulcerative Colitis
Dongsheng WU ; Yu ZHANG ; Wenjing QUAN ; Wanqing XIONG ; Bo ZOU ; Youwei XIAO ; Ruoru HUANG ; Yan GONG ; Hui CAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):69-75
ObjectiveTo investigate the role of the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway in intestinal mucosal barrier damage in ulcerative colitis, as well as the intervention mechanism of Shaoyaotang. MethodsSixty SD rats were allocated into a blank group, a model group, a mesalazine (0.42 g·kg-1) group, and low-, medium-, and high-dose (11.1, 22.2, 44.4 g·kg-1, respectively) Shaoyaotang groups. A model of ulcerative colitis was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). After successful modeling, rats were administrated with corresponding agents via gavage for 7 days. Changes in colon length and colon weight were observed. Hematoxylin-eosin staining was performed to examine the pathological changes of the colon, and immunohistochemistry was employed to detect the expression of the inflammatory cytokine interleukin-8 (IL-8), cyclooxygenase-2 (COX-2), junction adhesion molecule-1 (JAM-1), and claudin-1 in the colon. Western blot analysis was performed to determine the protein levels of TLR4, MyD88, and NF-κB in the colon. ResultsCompared with the blank group, the model group showed elevated DAI score (P<0.01), reduced colon length and colon weight (P<0.01), down-regulated protein levels of JAM-1 and claudin-1 (P<0.01), and up-regulated protein levels of IL-8, COX-2, TLR4, MyD88, and NF-κB p65 (P<0.01) in the colon tissue. Compared with the model group, each treatment group showed decreased DAI score (P<0.05, P<0.01), increased colon length and colon weight (P<0.05, P<0.01), up-regulated protein levels of JAM-1 and claudin-1 (P<0.01), and down-regulated protein levels of IL-8, COX-2, TLR4, MyD88, and NF-κB p65 (P<0.01) in the colon tissue. ConclusionShaoyaotang alleviates intestinal inflammation and intestinal mucosal damage to protect intestinal barrier integrity by regulating the TLR4/MyD88/NF-κB signaling pathway.
7.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
8.The first record of Anopheles messeae (Diptera: Culicidae) parasitized by water mites in China
Xue-ru CHEN ; Wen-zhen YAO ; Yu-hao LI ; Gui-chang LI ; Tao MENG ; Qun-ling FENG ; Xin-hui LIU ; Li-hong QIAO ; Xiang-ting WU ; Xue-feng ZHANG ; Cheng-lin LI ; Xue-cheng DONG ; Da-wei WANG ; Xiao-yan SI ; Yu-hong GUO
Acta Parasitologica et Medica Entomologica Sinica 2026;33(1):53-57
Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.
9.Application value of part-cut jejunal transection in digestive tract reconstruction of totally laparoscopic total gastrectomy
Heng JIANG ; Yingfeng ZHANG ; Jiahao WANG ; Yuancan WANG ; Yue WANG ; Qiushi PEI ; Jingjing TANG ; Sanwei CHEN ; Weixiang LI ; Hui YUAN ; Zhengsheng WU ; Yan ZHANG ; Lianbang ZHOU ; Yiping MOU
Chinese Journal of Digestive Surgery 2025;24(4):515-520
Objective:To explore the application value of part-cut jejunal transection in digestive tract reconstruction of totally laparoscopic total gastrectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 112 patients with gastric cancer who underwent totally laparoscopic total gastrectomy in The Second Affiliated Hospital of Anhui Medical University from June 2018 to September 2022 were collected. There were 81 males and 31 females, aged (70±8)years. Among the 112 patients, 60 patients undergoing diges-tive tract reconstruction by Roux-en-Y anastomosis with part-cut jejunum were set as the part-cut group, and 52 patients undergoing digestive tract reconstruction by traditional Roux-en-Y anasto-mosis were set as the traditional group. Observation indicators: (1) propensity score matching status and comparison of clinical data of patients between the two groups after matching; (2) intraopera-tive and postoperative conditions; (3) follow-up. Comparison of measurement data with normal dis-tribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Com-parison of ordinal data was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶1 nearest neighbor matching method, with the caliper value of 0.02. Results:(1) Propensity score matching status and comparison of clinical data of patients between the two groups after matching. Of the 112 patients, 90 patients were successfully matched, with 45 cases in each of the part-cut group and the traditional group. After propensity score matching, the elimination of body mass index, clinical TNM staging confounding bias ensured comparability. (2) Intraoperative and postoperative conditions. After propensity score matching, the total operation time and digestive tract reconstruction time of patients in the part-cut group were (217.0±15.1)minutes and (34.7±1.8)minutes, versus (252.6±21.9)minutes and (52.6±7.4)minutes in the traditional group, respectively, showing significant differences in the above indicators between the two groups ( t=?8.97, ?15.66, P<0.05). (3) Follow-up. After propensity score matching, 90 patients were followed up postoperatively for (47±15)months. During the follow-up, no patient in either group received secondary surgery, and there was no death. There were 3 cases and 10 cases of Roux stasis syndrome in the part-cut group and the traditional group, respectively, showing a significant difference between the two groups ( χ2=4.41, P<0.05). Conclusion:Compared with traditional Roux-en-Y anastomosis, the Roux-en-Y anastomosis with part-cut jejunum in totally laparoscopic total gastrectomy can signifi-cantly shorten the time for digestive tract reconstruction and reduce the incidence of postoperative Roux stasis syndrome.
10.Transcutaneous auricular vagus nerve stimulation regulates functional connectivity of thalamic subregions in patients with premenstrual syndrome
Ruijing SUN ; Yinqi LAI ; Ya CHEN ; Yuejuan WU ; Zhen LIU ; Qingping ZHANG ; Ziyan LAI ; Gaoxiong DUAN ; Yan ZHANG ; Shanshan LI ; Yuanyuan OU ; Sijing TUO ; Hui ZHOU ; Rongcai WU ; Zhizhong CHEN ; Demao DENG
Chinese Journal of Radiology 2025;59(12):1384-1392
Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.


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