1.Study on the relationship between inflammation index and the severity of cerebral small vessel disease
Qingqing WANG ; Shaoying WANG ; Hongjing WANG ; Lidi WANG ; Jingbing LI ; Cuiqing LIU
International Journal of Laboratory Medicine 2025;46(3):271-275
Objective To investigate the relationship between inflammation index and the severity of cere-bral small vessel disease.Methods A total of 168 patients with cerebral small vessel disease who were admit-ted to the Eighth People's Hospital of Hebei from August 2019 to October 2022 were selected as the study ob-jects.The study subjects were divided into cerebral small vessel disease with light burden(light burden group)and cerebral small vessel disease with medium-heavy burden(medium-heavy burden group)according to the total imaging burden score of cerebral small vessel disease.The basic data and systemic immune-inflam-matory index(SII),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),and monocyte to lymphocyte ratio(MLR)were compared between the two groups.Spearman correlation analysis was used to evaluate the correlation between SII,NLR,PLR and MLR and the total imaging burden score of cerebral small vessel disease,and the influence of SII,NLR,PLR and MLR on the medium-heavy burden of cerebral small vessel disease was further analyzed by multivariate Logistic regression.Receiver operating characteristic(ROC)curves were plotted to analyze the predictive value of SII,NLR,PLR and MLR in the severity of cere-bral small vessel disease.Results The age,smoking history,hypertension history,neutrophil,platelet,SII,NLR,PLR and MLR in medium-heavy burden group were significantly higher than those in light burden group,and lymphocyte was significantly lower than that in light burden group,with statistical significance(P<0.05).Spearman correlation analysis showed that SII(r=0.377),NLR(r=0.516),PLR(r=0.486)and MLR(r=0.391)were positively correlated with the total imaging burden score of cerebral small vessel disease(P<0.001).Multivariate Logistic regression analysis showed that age,neutrophil,platelet,SII,NLR,PLR and MLR were independent risk factors for medium-heavy burden in cerebral small vessel disease,and lymphocyte was independent protective factor for medium-heavy burden in cerebral small vessel disease(P<0.05).ROC curve analysis results showed that the area under the curve of SII,NLR,PLR and MLR separately detected were 0.720(95%CI:0.646-0.787),0.802(95%CI:0.733-0.859),0.784(95%CI:0.714-0.843)and 0.728(95%CI:0.654-0.794),respectively.The area under the curve of the combined detection of the four indexes was higher than that of the single detection of each index(P<0.05).Conclusion The combined detection of SII,NLR,PLR and MLR has high predictive value for the severity of cerebral small vessel dis-ease,and is worthy of clinical promotion.
2.Relationship between serum miR-30a-5p,RUNX2 and severity and prognosis of patients with sepsis-induced acute lung injury
Yuan TANG ; Qingqing ZHANG ; Yan LI ; Jian YANG ; Bin LUO ; Boqing WANG
International Journal of Laboratory Medicine 2025;46(8):948-954
Objective To investigate the relationship between serum microRNA-30a-5p(miR-30a-5p),Runt-associated transcription factor 2(RUNX2)and the severity and prognosis of patients with sepsis-induced acute lung injury(ALI).Methods A total of 193 patients with sepsis-induced ALI(ALI group)and 54 pa-tients with simple sepsis(non-ALI group)admitted to the Fifth Affiliated Hospital of Xinjiang Medical Uni-versity from January 2021 to February 2024 were selected,and the patients with sepsis-induced ALI were di-vided into a mild ALI group(57 cases),a moderate ALI group(64 cases),and a severe ALI group(72 cases)according to the oxygenation index,and were divided into a death group(71 cases)and a survival group(122 cases)according to the 28 day prognosis situation.Serum miR-30a-5p level was detected by real time fluores-cent quantitative PCR,serum RUNX2 level was detected by enzyme-linked immunosorbent assay,and the binding sites of miR-30a-5p and RUNX2 were predicted by online database.Pearson's correlation coefficient was used to analyze the correlation between miR-30a-5p and RUNX2 in patients with sepsis-induced ALI,and Spearman's correlation coefficient was used to analyze the correlation between serum miR-30a-5p,RUNX2 levels and oxygenation index in patients with sepsis-induced ALI.With the prognosis of patients with sepsis-induced ALI as the dependent variable,multivariate unconditional Logistic regression was used to determine their influencing factors,and receiver operating characteristic curve was plotted to evaluate the prognostic val-ue of serum miR-30a-5p and RUNX2 levels in patients with sepsis-induced ALI.Results Compared with the non-ALI group,serum miR-30a-5p level was lower and RUNX2 level was higher in the ALI group(t=-11.749,11.691,P<0.001).There was a binding site between miR-30a-5p and RUNX2 at the 3'-untranslat-ed region 3 348-3 354.miR-30a-5p was negatively correlated with RUNX2 in patients with sepsis-induced ALI(r=-0.759,P<0.001).The level of serum miR-30a-5p increased in the severe ALI group,the moderate ALI group and the mild ALI group in turn(P<0.001),and the level of RUNX2 decreased in the severe ALI group,the moderate ALI group and the mild ALI group in turn(P<0.001).Oxygenation index was negative-ly correlated with serum miR-30a-5p level(r=-0.749,P<0.001),and positively correlated with RUNX2 level in patients with sepsis-induced ALI(r=0.723,P<0.001).Independent protective factors for death in patients with sepsis-induced ALI were increased oxygenation index(OR=0.988,95%CI:0.981-0.996,P<0.05),elevated miR-30a-5p(OR=0.814,95%CI:0.744-0.892,P<0.05),and independent risk factors were increased Sequential Organ Failure Assessment(SOFA)score(OR=1.391,95%CI:1.116-1.734,P<0.05),elevated blood lactate(OR=1.824,95%CI:1.211-2.748,P<0.05),and elevated RUNX2(OR=1.366,95%CI:1.170-1.595,P<0.05).The area under the curve of serum miR-30a-5p and RUNX2 levels combined to predict the death in patients with sepsis-induced ALI was 0.895(95%CI:0.842-0.934),which was greater than 0.788(95%CI:0.724-0.844)of serum miR-30a-5p and 0.786(95%CI:0.721-0.842)of RUNX2 levels alone(Z=4.015,3.746,P<0.001).Conclusion Increased miR-30a-5p level and decreased RUNX2 level are associated with the aggravation of the disease and the increased risk of death in patients with sepsis-induced ALI.The combination of serum miR-30a-5p and RUNX2 levels has relatively high value in pre-dicting the prognosis of patients with sepsis-induced ALI.
3.Mechanisms of S100A10 regulating the proliferation and inflammation of psoriatic keratinocytes by targeting NF-κB and STAT3
International Journal of Biomedical Engineering 2025;48(2):165-173
Objective:To investigate the mechanisms of S100 calcium binding protein A10 (S100A10) regulating the proliferation and inflammation of psoriatic keratinocytes by targeting nuclear factor-κB (NF-κB) and signal transduction and activator of transcription 3 (STAT3).Methods:Skin lesion tissues from psoriasis patients (10 cases) and normal skin tissues from healthy control (10 cases) who underwent plastic surgery at the Department of Dermatology and Medical Cosmetology, Honghui Hospital Affiliated to Xi′an Jiaotong University from January to June 2024 were collected. The pCMV plasmid and small interfering RNA plasmid were transfected into human immortalized epidermal HaCaT cells to establish the S100A10 overexpression group and the S100A10 knockdown group, respectively. Untreated HaCaT cells were used as the control group. NF-κB and STAT3 pathway inhibitors were added to the cells in the S100A10 overexpression group to create two subgroups: the S100A10 overexpression+NF-κB inhibitor group and the S100A10 overexpression+STAT3 inhibitor group. The effect of S100A10 on HaCaT cell proliferation was determined by cell counting kit-8 assay. The effect of S100A10 on HaCaT cell apoptosis was detected by extracellular phosphatidylserine binding protein V-fluorescein isothiocyanate/ propidium iodide double staining. The expression of S100A10 in normal skin tissue and skin lesion tissues of psoriasis patients was detected by Western blotting. The relative expression of apoptosis-related protein cysteine aspartic acid specific protease-3 (Caspase-3) and NF-κB and STAT3 pathway-related proteins phosphorylated NF-κB p65 (p-NF-κB p65) and phosphorylated STAT3 (p-STAT3) was detected. The effects of S100A10 on the relative expression of interleukin (IL)-6, tumor necrosis factor-α ( TNF-α), IL-1β, and CXC chemokine ligand 8 ( CXCL8) mRNA were detected by real-time reverse transcription-PCR. The effects of S100A10 on the levels of IL-6, TNF-α, IL-1β and CXCL8 in cell supernatant were detected by enzyme-linked immunosorbent assay. One-way analysis of variance and independent t test were used for data analysis. Results:The expression of S100A10 protein in the skin lesion tissues of psoriasis patients was higher than that in normal skin tissues (1.58±0.13 vs 1.00±0.09, P<0.05). Compared with the control group, the cell survival rates of the S100A10 knockdown group [(99.89±1.03)% vs (82.24±6.03)%], the relative expression of p-NF-κB p65 (0.47±0.06 vs 0.21±0.03) and p-STAT3 protein (0.59±0.12 vs 0.17±0.03), the relative expression of IL-6 (0.98±0.12 vs 0.63±0.07), TNF-α (0.97±0.13 vs 0.71±0.09), IL-1β (1.02±0.14 vs 0.51±0.09) and CXCL8 mRNA (1.01±0.16 vs 0.59±0.11), the levels of IL-6 [(27.69±3.47) pg/ml vs (13.65±2.11) pg/ml], TNF-α [(19.21±2.16) pg/ml vs (10.06±1.44) pg/ml], IL-1β [(15.52±1.03) pg/ml vs (5.17±0.96) pg/ml] and CXCL8 [(62.87±8.48) pg/ml vs (47.11±6.35) pg/ml] in the cell supernatant were lower (all P<0.05), and the cell apoptosis rate [(15.41±2.37)% vs (26.38±4.16)%] and Caspase-3 protein relative expression (0.31±0.04 vs 0.74±0.12) were higher (both P<0.05). The cell survival rates [(145.24±6.03)%], the relative expression of p-NF-κB p65 and p-STAT3 protein (2.37±0.25, 3.98±0.47), the relative expression of IL-6, TNF-α, IL-1β and CXCL8 mRNA (2.27±0.64, 3.31±0.61, 2.74±0.43, 3.11±0.48), the levels of IL-6, TNF-α, IL-1β and CXCL8 in the cell supernatant [(51.17±7.95), (33.65±4.19), (29.95±4.07), (79.97±10.32) pg/ml] in the S100A10 overexpression group were higher than those in the control group (all P<0.05), and the cell apoptosis rate [(5.09±0.73)%] and Caspase-3 protein relative expression (0.09±0.01) were lower than those in the control group (both P<0.05). The cell survival rates [(123.65±9.42)%, (122.94±8.14)%], the relative expression of p-NF-κB p65 (1.51±0.19, 1.49±0.21) and p-STAT3 protein (1.67±0.29, 1.69±0.31), the relative expression of IL-6 (1.69±0.14, 1.73±0.15), TNF-α (1.92±0.27, 1.94±0.25), IL-1β (1.85±0.16, 1.87±0.21) and CXCL8 mRNA (2.02±0.34, 2.01±0.39), the levels of IL-6 [(35.55±5.12), (36.18±5.24) pg/ml], TNF-α [(25.17±3.08), (25.23±3.17) pg/ml], IL-1β [(22.08±3.11), (22.11±3.24) pg/ml] and CXCL8 [(70.04±9.31), (70.11±10.29) pg/ml] in the cell supernatant in the S100A10 overexpression+NF-κB inhibitor group and the S100A10 overexpression+STAT3 inhibitor group were higher than those in S100A10 knockdown group (all P<0.05), and the cell apoptosis rates [(20.13±4.62)%, (20.21±4.91)%] and Caspase-3 protein relative expression (0.15±0.03, 0.16±0.04) were lower than those in S100A10 knockdown group (all P<0.05).The cell survival rates, the relative expression of p-NF-κB p65 and p-STAT3 protein, the relative expression of IL-6, TNF-α, IL-1β and CXCL8 mRNA, the levels of IL-6, TNF-α, IL-1β and CXCL8 in the cell supernatant in the S100A10 overexpression+NF-κB inhibitor group and the S100A10 overexpression+STAT3 inhibitor group were lower than those in S100A10 overexpression group (all P<0.05), and the cell apoptosis rates and Caspase-3 protein relative expression were higher than those in S100A10 overexpression group (all P<0.05). Conclusions:S100A10 may regulate the proliferation and inflammation of keratinocytes in psoriasis by targeting NF-κB and STAT3.
4.Clinical application value of three-dimensional visualization technology in the precise diagnosis and treatment of locally advanced differentiated thyroid cancer
Hai YAN ; Jian ZHU ; Dan WANG ; Changrui LIU ; Yixin LIU ; Dongliang ZHAI ; Yuanyuan LIU ; Yuan LI ; Qingqing HE
International Journal of Surgery 2025;52(1):19-27
Objective:To investigate the feasibility and effectiveness of three-dimensional visualization technology in the precise diagnosis and treatment of locally advanced differentiated thyroid cancer(DTC).Methods:A retrospective analysis was conducted on the clinical data of 196 patients with locally advanced DTC treated at the 960th Hospital of the PLA from December 2021 to August 2023. The cohort included 71 male and 125 female patients, with a mean age of 43.7 years (rangd from 18 to 77 years). All patients underwent neck-enhanced CT scans and were divided into two groups: the study group( n=102), which underwent preoperative three-dimensional visualization of CT data, and the control group( n=94), which did not. Baseline data for both groups were matched using SPSS27.0 with 1∶1 propensity score matching (PSM) and the caliper value was 0.02. A total of 49 patients were included in each group, including 35 first-time surgeries and 14 reoperation. Among the 70 first-time surgeries, 29 patients underwent robotic surgery and 41 underwent open surgery. Among the 28 reoperations, 4 underwent robotic surgery and 24 underwent open surgery. In the study group, three-dimensional visual models were used to comprehensively evaluate the tumor and metastatic lesion size, spatial location, and adjacent relationship with surrounding organs, surgical treatments were guided by these models, whereas the control group relied on two-dimensional imaging for guidance. The clinical data were statistically analyzed using SPSS27.0. Results:All operations were successfully completed. There were no statistical differences in baseline data between the two groups( P>0.05). Among first-time surgeries, the study group showed shorter operation times [175(145, 200) min vs 205(182, 249) min, P<0.001], a lower incidence of postoperative chyle leak (0 vs 8.57%, P=0.027), a higher rate of robotic surgery (48.57% vs 34.28%, P=0.225), a greater number of harvested lymph nodes [46(40, 62) vs 37(28, 56), P=0.032], a greater number of cervical lymph node metastasis[15(7, 22) vs 5(1, 14), P=0.004] and a larger diameter of metastasis lymph nodes[12(10, 16) mm vs 4(1, 10) mm, P<0.001]. There were no significant differences in intraoperative blood loss, postoperative drainage days and incidence of hypoparathyroidism( P>0.05). During the reoperation, the study group had shorter operation times[103.5(95.0, 122.5) min vs 146.50(133.25, 172.25) min, P<0.001], less intraoperative blood loss[12.50(8.75, 22.50) mL vs 30.00(17.50, 35.00) mL, P=0.021], fewer postoperative drainage days[5.00(4.00, 6.00) d vs 6.00(5.00, 7.25) d, P=0.016] and a lower incidence of hypoparathyroidism(7.14% vs 42.86%, P=0.038).The robotic surgery rate was higher in the study group (21.42% vs 7.14%, P=0.596). There were no significant differences in lymph node dissection numbers, metastatic lymph node counts, or chyle leak incidences between the two groups ( P>0.05). No acute bleeding or incision infection occurred in any patient postoperatively. Conclusion:Three-dimensional visualization technology is an effective preoperative assessment method for evaluating the resectability of tumors and metastases lesions in locally advanced DTC. It enhances the accuracy and safety of surgery for locally advanced DTC.
5.Exploration of the application of vehicle-mounted 5G remote mobile robotic surgical system in thyroid surgery
Meng WANG ; Wen TIAN ; Qingqing HE ; Guolou LI ; Jian ZHU ; Xiaodong MA ; Wei WEI ; Qiongqiong TAN ; Jinzhi HU ; Yingying WANG ; Peng ZHOU ; Gang WANG ; Yixin LIU ; Hejun WANG ; Yu LIU ; Lihu LIU
International Journal of Surgery 2025;52(1):28-32
Objective:To investigate the feasibility and safety of implementing a domestic vehicle-mounted remote mobile robotic surgical system in thyroid surgery applications, integrated with 5G communication technology.Methods:Using the main system located on the vehicle-mounted mobile robot operating platform of the 960th Hospital of PLA Joint Logistics Support Force and the slave system of Weifang Traditional Chinese Hospital, the remote radical thyroidectomy 5G communication technology, and analyze the clinical and information transmission data of two female patients who underwent remote mobile robot thyroid cancer surgery on October 21, 2024 at Weifang Traditional Chinese Medicine Hospital.Results:The remote radical thyroidectomy was conducted by the robosurgeons utilizing a vehicle-mounted mobile robotic surgical system, and the procedure was successfully completed without necessitating intermediate open surgery. The operation durations for patient 1 and patient 2 were 135 minutes and 108 minutes, respectively, with 7 and 13 lymph nodes dissected, respectively. The average delay in surgical data transmission was recorded at 61.9 milliseconds, with no instances of signal interruption or frame loss. The procedure proceeded smoothly, without any jamming, and the audio and video transmissions were consistently clear. Follow up for 21 days after surgery showed no complications such as hoarseness, skin damage, or lymphatic fistula.Conclusion:The implementation of a vehicle-mounted remote mobile robotic surgery system for thyroid surgery has demonstrated safety and feasibility. Furthermore, the utilization of the 5G network offers rapid data transmission and minimal latency, closely approximating the therapeutic efficacy of traditional robotic thyroidectomy.
6.Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women
Claudia Ha-ting TAM ; Ying WANG ; Chi Chiu WANG ; Lai Yuk YUEN ; Cadmon King-poo LIM ; Junhong LENG ; Ling WU ; Alex Chi-wai NG ; Yong HOU ; Kit Ying TSOI ; Hui WANG ; Risa OZAKI ; Albert Martin LI ; Qingqing WANG ; Juliana Chung-ngor CHAN ; Yan Chou YE ; Wing Hung TAM ; Xilin YANG ; Ronald Ching-wan MA
Diabetes & Metabolism Journal 2025;49(1):128-143
Background:
The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.
Methods:
We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.
Results:
Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.
Conclusion
Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.
7.Zishen Tiaogan Prescription Treats Diminished Ovarian Reserve in Rats via Keap1/Nrf2/HO-1 Signaling Pathway
Zhongtong LI ; Yaping ZHANG ; Chen YOU ; Qingqing LI ; Yingjie WANG ; Siwen OU ; Taomei XUE ; Chuqi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):72-80
ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve (DOR) and explore the role of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group (n=12) and a modeling group (n=36). The rats in the modeling group received subcutaneous injection of galactose (350 mg·kg-1) combined with immobilization stress daily. After 28 days of modeling, 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model, estradiol valerate (0.09 mg·kg-1), and low-, medium-, and high-dose (6.39, 12.78, 25.56 g·kg-1, respectively) Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels, respectively, of Nrf2, Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 (SOD2) in the ovarian tissue was detected by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed reduced follicles in the ovary, loose arrangement of the follicle granule layer, declined levels of anti-Mullerian hormone (AMH) and estradiol (E2) in the serum, elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (P<0.01), lowered levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) (P<0.01), and increased accumulation of malondialdehyde (MDA) (P<0.01). In addition, the modeling led to up-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 and HO-1 protein was significantly decreased (P<0.01), the mRNA expression of Nrf2 was significantly decreased (P<0.05), the mRNA expression of HO-1 was significantly decreased (P<0.01), in the ovarian tissue. Compared with model group, the estradiol valerate and low-, medium-, and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index (P<0.01) and serum E2 and AMH levels (P<0.01), declined levels of FSH and LH (P<0.01), increased follicles in the ovary, elevated levels of SOD, CAT, and GSH, and reduced accumulation of MDA (P<0.05, P<0.01). Furthermore, these groups showcased down-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 protein was significantly increased (P<0.01), the expression level of HO-1 protein was increased (P<0.05,P<0.01), and increased positive expression of SOD2 (P<0.01). ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones, down-regulate the expression of Keap1, up-regulate the expression of Nrf2, HO-1, and SOD2, enhance the antioxidant capacity, and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.
8.Zishen Tiaogan Prescription Treats Diminished Ovarian Reserve in Rats via Keap1/Nrf2/HO-1 Signaling Pathway
Zhongtong LI ; Yaping ZHANG ; Chen YOU ; Qingqing LI ; Yingjie WANG ; Siwen OU ; Taomei XUE ; Chuqi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):72-80
ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve (DOR) and explore the role of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group (n=12) and a modeling group (n=36). The rats in the modeling group received subcutaneous injection of galactose (350 mg·kg-1) combined with immobilization stress daily. After 28 days of modeling, 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model, estradiol valerate (0.09 mg·kg-1), and low-, medium-, and high-dose (6.39, 12.78, 25.56 g·kg-1, respectively) Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels, respectively, of Nrf2, Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 (SOD2) in the ovarian tissue was detected by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed reduced follicles in the ovary, loose arrangement of the follicle granule layer, declined levels of anti-Mullerian hormone (AMH) and estradiol (E2) in the serum, elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (P<0.01), lowered levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) (P<0.01), and increased accumulation of malondialdehyde (MDA) (P<0.01). In addition, the modeling led to up-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 and HO-1 protein was significantly decreased (P<0.01), the mRNA expression of Nrf2 was significantly decreased (P<0.05), the mRNA expression of HO-1 was significantly decreased (P<0.01), in the ovarian tissue. Compared with model group, the estradiol valerate and low-, medium-, and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index (P<0.01) and serum E2 and AMH levels (P<0.01), declined levels of FSH and LH (P<0.01), increased follicles in the ovary, elevated levels of SOD, CAT, and GSH, and reduced accumulation of MDA (P<0.05, P<0.01). Furthermore, these groups showcased down-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 protein was significantly increased (P<0.01), the expression level of HO-1 protein was increased (P<0.05,P<0.01), and increased positive expression of SOD2 (P<0.01). ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones, down-regulate the expression of Keap1, up-regulate the expression of Nrf2, HO-1, and SOD2, enhance the antioxidant capacity, and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.
9.Treating immunoglobulin A nephropathy based on the " qi cycle in round" theory
Leying ZHAO ; Yaoxian WANG ; Zhen WANG ; Yaotan LI ; Boning CAO ; Jiayin TAO ; Danting LI ; Qingqing LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):223-228
Immunoglobulin A (IgA) nephropathy is a globally prevalent type of primary glomerulonephritis, characterized by complex symptoms and diverse clinical manifestations. The internationally recognized " multiple hit hypothesis" explains the systemic immune disease features of IgA nephropathy. However, current treatment strategies primarily focus on local pathological changes, inadequately addressing its complex systemic mechanisms. The " qi cycle in round" theory, an integral concept of the academic thought of HUANG Yuanyu, a prominent medical expert from the Qing Dynasty, offers a concise and insightful framework for understanding complex pathologies. For example, this theory provides valuable insights for elucidating the pathogenesis of IgA nephropathy and guiding its clinical management by simplifying intricate systemic processes. This study applies the " qi cycle in round" theory to postulate that patients with IgA nephropathy experience disrupted qi flow owing to spleen-stomach qi deficiency and dampness-heat accumulation. These imbalances manifest as internal symptoms, such as diarrhea; external vulnerability to illness; upper body symptoms, like sore throat; and lower body symptoms, such as hematuria and proteinuria. Pathologically, the condition is characterized by immune complex deposition. This article also emphasizes strategies that prioritize tonifying spleen-stomach qi to enhance the pivotal functions of transportation and transformation. Regulating qi and relieving stagnation are emphasized to harmonize ascending and descending dynamics. Additionally, eliminating turbidity and unblocking collaterals are highlighted to promote qi transformation. These approaches aim to restore the harmonious operation of organ qi dynamics and harmonious qi transformation functions. This study aims to provide a reference for syndrome differentiation and IgA nephropathy treatment using traditional Chinese medicine based on the " qi cycle in round" theory.
10.Effect of Dachaihu decoction on dextran sodium sulfate-induced ulcerative colitis and liver injury and its association with gut microbiota modulation in mice
Qingqing XIANG ; Feng LAI ; Hong XIAO ; Zhengjia PU ; Lingli MA ; Xiangyun LIU ; Shihui LI ; Shengmin MAO ; Jiarui FAN ; Yuchen LI ; Ankang LI ; Yang WANG ; Qunhua BAI
Journal of Chongqing Medical University 2025;50(8):1084-1095
Objective:To investigate the preventive and therapeutic effects and mechanisms of Dachaihu decoction(DCD)on dextran sodium sulfate(DSS)-induced ulcerative colitis(UC)and liver injury in mice,as well as the association between DCD benefits and gut microbiota modulation.Methods:Mice were treated with DCD(20.10 and 10.05 g/kg)for 2 weeks,with free access to drinking water containing 3%DSS in the second week to induce UC.Histopathological examination,RT-qPCR and 16S rRNA sequencing were used to investigate the effect of DCD on UC mice.Results:DCD pretreatment significantly alleviated weight loss,bloody diarrhea with mucus,histopathological abnormalities of the colon,and colon shortening in mice with DSS-induced UC.In addition,DCD pretreat-ment significantly upregulated the levels of Occludin,ZO-1,and MUC-2 in the colon and protected the intestinal barrier of mice.DCD pretreatment also alleviated inflammatory cell infiltration in the colon and the liver and significantly reduced the expression levels of the proinflammatory factors such as IL-1β,IL-6,TNF-α,iNOS,COX-2,and NLRP3,thereby exerting a protective effect against UC and liver injury.It should be noted that DCD corrected gut micro-biota imbalance in UC mice by enriching probiotic bacteria such as Lactobacillus and Bifidobacterium and reducing harmful bacteria such as Norank_f_Desulfovibrionaceae and Escherichia-Shigella.Conclusion:DCD can alleviate DSS-induced UC and exert a liver-protecting effect by protecting intestinal barrier,inhibiting inflam-mation,and regulating gut microbiota.


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