1.Sesquiterpene ZH-13 from Aquilariae Lignum Resinatum Improves Neuroinflammation by Regulating JNK Phosphorylation
Ziyu YIN ; Yun GAO ; Junjiao WANG ; Weigang XUE ; Xueping PANG ; Huiting LIU ; Yunfang ZHAO ; Huixia HUO ; Jun LI ; Jiao ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):139-145
ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide (LPS) to induce neuroinflammation. The cells were divided into the normal group, the model group, and the ZH-13 low- and high-dose treatment groups (10, 20 μmol·L-1). The model group was treated with 1 μmol·L-1 LPS. Cell viability was assessed using the cell proliferation and activity assay (CCK-8 kit). Nitric oxide (NO) release in the cell supernatant was measured using a nitric oxide kit (Griess method). The mRNA expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and interleukin-6 (IL-6) were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The phosphorylation of mitogen-activated protein kinase (MAPK) pathway proteins was assessed by Western blot. ResultsCompared with the model group, ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation (P<0.05, P<0.01). In the 20 μmol·L-1 ZH-13 treatment group, the mRNA expression levels of IL-1β, TNF-α, iNOS, and IL-6 were significantly reduced compared to the model group (P<0.05, P<0.01). In both the low- and high-dose ZH-13 groups, the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase (JNK) in the upstream MAPK pathway were significantly reduced (P<0.05). After stimulation with the JNK agonist anisomycin (Ani), both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group (P<0.01). ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.
2.Trend of Cervical Cancer Incidence and Age Change in Cancer Registration Areas of Jiangsu Province from 2009 to 2019
Lingling WU ; Fudong LIU ; Weigang MIAO ; Renqiang HAN ; Jinyi ZHOU ; Pengfei LUO
Cancer Research on Prevention and Treatment 2024;51(11):945-950
Objective To analyze the changing trends of the incidence and onset age of cervical cancer in Jiangsu Province by using cancer registration data from 2009 to 2019. Methods The information of national cancer registries with continuous data from 2009 to 2019 was selected, and the quality control indices of cancer registration must be up to standards. A total of 16 registries were included in this study. Statistical analysis indicators include the crude incidence rate of cervical cancer, age-standardized incidence rate, actual average onset age, age-standardized average onset age, and average annual percentage change (AAPC). A birth cohort model was constructed to analyze the incidence of cervical cancer among women born from 2009 to 2019 and its incidence trend. Results From 2009 to 2019, the crude and age-standardized incidence rates of cervical cancer among women in Jiangsu Province showed upward trends, with AAPCs of 5.62% (95%CI: 3.47−7.82) and 4.14% (95%CI: 2.06−6.27), respectively. The incidence rate of cervical cancer in rural areas (AAPC=4.46, 95%CI: 1.13−7.91) increased more than that in urban areas (AAPC=3.83, 95%CI: 2.81−4.86). The actual average onset age of cervical cancer increased from 51.53 years in 2009 to 55.07 years in 2019 (β=0.36, P<0.05). The age-standardized average onset age increased from 48.89 years in 2009 to 50.43 years in 2019 (β=0.21, P<0.05). The age composition ratios of cervical cancer in the age group of 60 years and older were 31.90% in 2019 and 22.40% in 2009 (β=3.66, P<0.05). The incidence of cervical cancer in the same age group of people with different birth years showed an upward trend with the increase in birth year. Conclusion From 2009 to 2019, the incidence rate of cervical cancer in Jiangsu Province showed an upward trend, and this trend was more obvious in rural areas than in urban areas. In addition, the average onset age of cervical cancer showed an upward trend.
3.Effect of nasal microbial diversity on postoperative prognosis of patients with chronic sinusitis and nasal polyp
Weigang GAN ; Xingchen LIU ; Feng LIU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(8):828-836
Objective:To investigate the nasal microbial diversity in patients with chronic sinusitis with nasal polyps (CRSwNP), as well as the nasal microbiome characteristics, inflammatory cells and factors in postoperative relapses, in order to understand the effects of microbiome factors on the postoperative prognosis of CRSwNP.Methods:The nasal secretions and nasal polyp tissues from 77 patients with CRSwNP were collected in Department of Otorhinolaryngology Head and Neck Surgery, West China Hospital, Sichuan University from December 2017 to December 2018. The cohort consisted of 34 males and 43 females, aged from 29 to 76 years. Microbial DNA was extracted from cotton swabs for high-throughput sequencing based on 16SrRNA to detect bacterial community composition, and Luminex was used to analyze cytokines such as IL-5, IL-8, IL-17a, IL-17e, IL-18, IL-27, and IFN-γ in polyp tissue. Eosinophils and neutrophils in peripheral blood and polyp tissue were counted. Patients with CRSwNP were followed up for 1 year after surgery, and the recurrence of nasal polyps was recorded. The correlation between the recurrence of nasal polyps and inflammatory cytokines, inflammatory cell counts and nasal microbial diversity was analyzed. Chi-square test was used for bicategorical variables, Mann-Whitney U test was used for continuous variables, and Wilcoxon rank sum test was used to compare the difference in average relative abundance between the two groups.Results:At the one year follow-up, 12 patients experienced a recurrence, including 5 males and 7 females. There was no significant difference in age, sex, asthma, allergic rhinitis and eczema between the relapsing group and the non-relapsing group. The total nasal symptoms score (TNSS) in the recurrent group [42.3 (30.2, 67.1), M ( Q1, Q3)] was significantly higher than that in the non-recurrent group [37.8 (29.4, 50.3)]. In nasal polyp tissue, the number of eosinophils [40.83 (22.33, 102.00)/HP] and neutrophils [30.83 (20.33, 56.44)/HP] in the recurrent group were significantly higher than those in the non-recurrent group [13.72 (13.50, 48.33)/HP] and [18.50 (12.00, 26.08)/HP], Z-values were -6.997 and -8.243, respectively, all P<0.001. The expression levels of IFN-γ, IL-17A, IL-17E and IL-18 in relapsed group were significantly higher than those in non-relapsed group, but there was no significant difference in positive rates. At the generic level, the mean relative abundance of Corynebacterium in the nasal passage of CRSwNP patients in the non-relapses group was (11.90±20.31)%, higher than that in the relapses group (0.15±0.20)%, but the difference was not statistically significant after correction (FDR P=0.638). The mean relative abundance of staphylococcus in the non-relapsed group was (8.17±27.70)%, significantly lower than that in the relapsed group (8.99±15.89)%, but the difference was not statistically significant (FDR P=0.638). Conclusions:Neutrophil-mediated inflammatory responses are associated with recurrent nasal polyps. The recurrence of nasal polyps after endoscopic surgery may be related to the decrease in the abundance of protective microorganisms and the increase in the number of pathogenic microorganisms.
4.Efficacy and safety of whole-brain low-dose radiotherapy combined with ICI and intrathecal chemotherapy for leptomeningeal metastases from lung cancer
Xiang LISHA ; Zhang XUANWEI ; Yu MIN ; Xiu WEIGANG ; Zou BINGWEN ; Xu YONG ; Liu YONGMEI ; Zhou LIN ; Xue JIANXIN ; Lu YOU
Chinese Journal of Clinical Oncology 2024;51(18):943-949
Objective:To explore the efficacy and safety of whole-brain low-dose radiotherapy(LDRT)combined with PD-1 inhibitor sin-tilimab and intrathecal pemetrexed(IP)for the treatment of refractory non-small cell lung cancer(NSCLC)with leptomeningeal metastases(LM).Methods:Retrospective analysies were was performed on eight NSCLC patients with LM at the West China Hospital of Sichuan Uni-versity from December 2022 to May 2024.Among the eight patients,there were four were males and four were females,with a median age of 49 years(rangeing,between 34 to 58 years).All patients were treated with whole-brain LDRT combined with immune checkpoint inhibit-or(ICI)and intrathecal chemotherapy regimens,and the therapeutic efficacy was evaluated according to the Response Assessment in Neuro-Oncology(RANO)criteria and the Karnofsky physical status(KPS)score.Adverse reactions were assessed according to the Common Criteria for the Evaluation of Adverse Events(CTCAE version 5.0).Survival analysis was performed using the Kaplan-Meier method.The classification proportion of cerebrospinal fluid subsets before and after treatment was analyzed using by single-cell sequencing,and the differential ana-lysis of gene expression in parallel cells was performed.Results:The best clinical treatment effects in eight patients were were evaluated us-ing the RANO criteria:five patients(62.5%)were evaluated as improved and three(37.5%)as stable.The median KPS score of the eight pa-tients was 30(20-50)before treatment,which was significantly improved to 60(40-90)after treatment(P=0.000 9).The remission rate of neurological symptoms was 100%(8/8)in eight patients.The median neurological progression-free survival(NPFS)was 12 months.The res-ults of single-cell sequencing in CSF of patientss(P1)showed that the proportion of T cells in the patient samples after whole-brain LDRT treatment was significantly higher than that before treatment(6.08%vs.68.87%),and the proportion of tumor cells was significantly lower(12.92%vs.0.6%).The differential analysis of gene expression showed that CCL5 and CXCL13 were significantly upregulated in T cells of CSF after WB-LDRT treatment.Conclusions:The combination of whole-brain LDRT with ICI and IP in the treatment of NSCLC with LM can signific-antly alleviate neurological symptoms,improve quality of life and prolong the NPFS of patients,which is a safe and effective treatment.
5.Effect of Probiotics on Bile Acid Metabolism via FXR-FGF19 Pathway in Patients With Choledocholithiasis
Lüwang YE ; Cong WANG ; Junwei FAN ; Ting JIANG ; Mengyan DU ; Weigang CHEN ; Fang LIU
Chinese Journal of Gastroenterology 2024;29(1):10-14
Background:Recurrence after stone removal is common in patients with choledocholithiasis.Recent studies have indicated that dysbiosis in gut microbiota plays an important role in the formation of cholesterol gallstones.Aims:To explore the effect of probiotics supplementation on serum lipopolysaccharide(LPS)and the indicators of bile acid metabolism in patients with a high risk of cholesterol gallstone formation.Methods:Sixty choledocholithiasis patients undergoing ERCP lithotomy were recruited at the First Affiliated Hospital of Shihezi University from June 2021 to June 2023.Bile and stool samples were collected for bacterial culture.Then the patients were randomly allocated into two groups:patients in control group received conventional supportive therapy after calculus removal,while those in probiotics intervention group were given oral bifid triple viable enteric capsule 420 mg,twice a day for 6 months based on conventional therapy.Changes in serum levels of LPS,the cell wall component of Gram-negative bacteria,fibroblast growth factor 19(FGF19),the key molecule in bile acid metabolism,and cholesterol 7α-hydroxylase(CYP7A1),the rate-limiting enzyme of bile acid synthesis,were determined and compared between the two groups.Results:Escherichia coli and Klebsiella pneumoniae were the main pathogens in bile and stool of patients with choledocholithiasis.Six months after ERCP lithotomy,the serum levels of LPS and FGF19 were decreased,and the serum level of CYP7A1 was increased in both groups(all P<0.05),especially in probiotics intervention group(all P<0.05).Conclusions:Oral probiotics supplementation can reduce the serum LPS level and modulate the canonical pathway of enterohepatic circulation of bile acids--farnesoid X receptor(FXR)-FGF19 pathway in high-risk patients of cholesterol gallstone formation.These alterations reduce the cholesterol supersaturation in bile and inhibit the probability of cholesterol gallstone formation.
6.The characteristics of gut microbiota in patients with type 2 diabetes mellitus and concurrent nonalcoholic fatty liver disease
Yuting GAO ; Tianyi ZHAO ; Shixuan LIU ; Na LV ; Tao YUAN ; Junxiang GAO ; Baoli ZHU ; Weigang ZHAO
Chinese Journal of Clinical Nutrition 2024;32(2):80-89
Objective:To investigate the characteristics of gut microbiota in patients with type 2 diabetes (T2DM) complicated by nonalcoholic fatty liver disease (NAFLD).Methods:A total of 74 patients first diagnosed with T2DM at the Endocrinology Department of Peking Union Medical College Hospital from April 2021 to October 2023 were included. Among them, 28 patients had concurrent NAFLD while 46 patients did not. Additionally, 51 healthy controls were matched (HC group). Clinical laboratory parameters were collected, and 16S rRNA sequencing with fecal samples was conducted to compare the differences in gut microbiota across the groups.Results:Compared to the group with T2DM, patients with concurrent T2DM and NAFLD were younger, had higher level of insulin resistance as assessed by the homeostatic model assessment of insulin resistance, higher body mass index (BMI), and higher triglyceride levels. There was no difference in α-diversity across the three groups ( P>0.05), while there was a significant difference in β-diversity ( P=0.03). The Eubacterium coprostanoligenes, Fusicatenibacter, Parasutterella and Tyzzerella 3 were enriched in the group with concurrent T2DM and NAFLD as shown by the relative abundance, while the relative abundance of Flavonifractor was decreased in this group. Tyzzerella 3 abundance was positively correlated with triglyceride and albumin levels and negatively correlated with high-density lipoprotein cholesterol (HDL-C) levels. Conclusion:Patients with T2DM complicated by NAFLD exhibit dysbiosis in gut microbiota composition and specific genera abundance, with Flavonifractor identified as a potential protective factor for T2DM complicated by NAFLD.
7.Analysis of anxiety and depressive status and influencing factors in patients with colorectal polyps in part of Xinjiang area
Xuejiao TAN ; Yaqiong PENG ; Xin PENG ; Miaomiao LUO ; Jian QIN ; Jiaxue LI ; Lina YE ; Ronghui PU ; Li LAI ; Jiajing MA ; Qinglin ZHANG ; Fang LIU ; Weigang CHEN
Chinese Journal of Digestion 2023;43(7):472-480
Objective:To investigated the prevalence of anxiety and depression symptoms in patients with colorectal polyps in part of Xinjiang area and to explore the associated influencing factors related to psychological status, and to provide evidence and clues to promote the diagnosis and treatment of psychosomatic diseases in digestive system.Methods:From December 2021 to June 2022, at the First Affiliated Hospital of Shihezi University, the Fourth Division Hospital of Xinjiang Production and Construction Corps, the Third Division Hospital of Xinjiang Production and Construction Corps (Kashgar Hospital), the Thirteenth Division Red Star Hospital of Xinjiang Production and Construction Corps, the Tenth Division Beitun Hospital of Xinjiang Production and Construction Corps, the Seventh Division Hospital of Xinjiang Production and Construction Corps, the Fifth Division Hospital of Xinjiang Production and Construction Corps, patients who underwent colonoscopy and colorectal polyps detected were enrolled. The generalized anxiety disorder scale-7 (GAD-7) was used to screen anxiety symptoms, and the patient health questionaire-8 (PHQ-8) was performed to screen depression symptoms, and the general situation questionnaire was used to collect clinical information of patients. The questionnairs were completed via the Questionnaire Star platform or paper questionnaire, and a database was established. The patients were divided into groups according to whether with anxiety and depression symptoms. Multivariable logistic regression models was performed to analyze the factors related to anxiety and depression.Results:A total of 516 questionnaires were distributed and collected, among which 9 questionnaires were incomplete and 507 questionnaires were valid, the effective rate of questionnaires was 98.26%. The detection rates of anxiety and depression symptoms in 507 patients with colorectal polyps were 21.50%(109/507) and 19.33%(98/507), respectively. The results of multivariable logistic analysis revealed that female ( OR=3.87, 95% confidence interval (95% CI) 2.30 to 6.51, P<0.001), maximum diameter of polyp ( OR=1.74, 95% CI 1.14 to 2.67, P=0.011), perception of polyps as cancer ( OR=13.96, 95% CI 1.48 to 132.07, P=0.022), and the occurrence of gastrointestinal symptoms after polyp detection ( OR=5.43, 95% CI 1.74 to 16.92, P=0.004) were independent risk factors of anxiety in patients with colorectal polyps. Female ( OR=2.42, 95% CI 1.47 to 4.00, P=0.001), the number of polyps ( OR=1.07, 95% CI 1.01 to 1.13, P=0.028) and the count of gastrointestinal symptoms ( OR=2.04, 95% CI 1.34 to 3.10, P=0.001) were independent risk factors of depression in patients with colorectal polyps. Conclusion:Gender, polyp size, number of polyps, disease perception, and concomitant gastrointestinal symptoms are associated with anxiety and depression in patients with colorectal polyps.
8.Association between visibility of deep medullary vein and pathogenesis of recent small subcortical infarct
Yuanyuan YIN ; Weigang LUO ; Wanhu LIU ; Yuzhu XU ; Xiaoyun CAO ; Huiling REN
Chinese Journal of Neuromedicine 2022;21(11):1090-1096
Objective:To evaluate the visibility of intracranial deep medullary vein (DMV) by sensitivity weighted imaging (SWI), and explore its correlation with recent small subcortical infarct (RSSI).Methods:From March 2021 to May 2022, 277 patients with cerebral small vascular disease (CSVD) confirmed by cranial MRI in Department of Neurology, Third Hospital of Hebei Medical University, were consecutively enrolled. These patients were divided into RSSI group ( n=128) and non-RSSI group ( n=149) according to RSSI presence or not within one week of onset. According to the DMV scores, these patients were divided into mild-moderate DMV group (0-12 scores, n=199) and severe DMV group (13-18 scores, n=78). The clinical and imaging data of these groups were analyzed retrospectively and compared. Multivariate Logistic regression analysis was used to determine the correlation between DMV and RSSI, as well as the independent influencing factors for DMV grading. Results:The cerebral microbleed (CMB), periventricular white matter hyperintensity (WMH) scores, deep WMH scores, total WMH scores, total CSVD burden scores, and DMV scores in patients of the RSSI group were significantly higher than those in the non-RSSI group ( P<0.05); and patients in the RSSI group had significantly younger age and significantly lower high density lipoprotein cholesterol (HDL-C) level than those in the non-RSSI group ( P<0.05). Multivariate Logistic regression analysis showed that DMV score ( OR=1.142, 95%CI: 1.026-1.271, P=0.016) was an independent influencing factor for RSSI after adjusting for HDL-C and deep WMH scores. The severe DMV group had significantly older age, statistically higher percentages of patients having history of hypertension, CMB, lacuna and moderate to severe EPVS in basal ganglia, and significantly higher periventricular WMH scores, deep WMH scores, total WMH scores, and total CSVD burden scores as compared with the mild-moderate DMV group ( P<0.05). Multivariate Logistic regression analysis showed that age ( OR=1.101, 95%CI: 1.060-1.143, P<0.001) and total CSVD burden scores ( OR=3.589, 95%CI: 2.506-5.141, P<0.001) were independent influencing factors for DMV scores. Conclusion:DMV is involved in the mechanism of RSSI, and DMV visibility can be used as an indicator to diagnose RSSI and evaluate RSSI progression.
9.Application of the pedicled pericranial flap in the treatment of chronic cerebrospinal fluid leakage
Tingting XIANG ; Weimin WU ; Lixia WEN ; Yapeng LIU ; Weigang HU ; Ming XIA
Chinese Journal of Plastic Surgery 2022;38(7):787-791
Objective:To investigate the effect of the pedicled pericranial flap in the treatment of chronic cerebrospinal fluid leakage.Methods:A retrospective analysis was conducted based on the clinical data of patients with cerebrospinal fluid leakage after craniocerebral surgery who were admitted to the First People’s Hospital of Yichang from April 2016 to October 2020. The necrotic tissues were thoroughly removed. The dural defects were repaired with pedicled pericranial flaps, and soft tissue defects were repaired with local flaps. The incision was covered with negative pressure closed drainage dressing, and negative pressure was maintained at -50 to -80 mmHg (1 mmHg=0.133 kPa). Cerebrospinal fluid leakage, defect repair, and related complications were observed in postoperative follow-up.Results:A total of five patients (three males and two females, aged 49-65 years) were included. All patients had postoperative composite tissue defects with local infection after craniocerebral surgery, lasting two months to 12 years. The size of the postoperative dural defect ranged from 1.5 cm × 2.0 cm to 2.5 cm × 3.0 cm. The size of the scalp soft tissue defect ranged from 2.0 cm × 2.0 cm to 3.0 cm × 6.0 cm. The size of the pericranial flap ranged from 2.0 cm × 3.0 cm to 3.0 cm × 3.5 cm, and the local flap ranged from 8.0 cm × 13.0 cm to 12.0 cm × 16.0 cm. The cerebrospinal fluid leakage was still observed in one patient at 5 d after the surgery and was treated with continuous lumbar pool puncture for cerebrospinal fluid drainage, which healed one week later. One patient suffered from poor healing of the flap incision, which healed after two weeks of outpatient dressing changing. At the postoperative follow-up of 3 to 17 months, none had any further cerebrospinal fluid leakage, and no other complications such as intracranial infection, loss of frontal lines, scalp numbness, and necrosis occurred.Conclusions:Repair of dural defects by pedicled pericranial flaps can treat chronic cerebrospinal fluid leakage with less damage to the donor site and fewer complications.
10.Application of the pedicled pericranial flap in the treatment of chronic cerebrospinal fluid leakage
Tingting XIANG ; Weimin WU ; Lixia WEN ; Yapeng LIU ; Weigang HU ; Ming XIA
Chinese Journal of Plastic Surgery 2022;38(7):787-791
Objective:To investigate the effect of the pedicled pericranial flap in the treatment of chronic cerebrospinal fluid leakage.Methods:A retrospective analysis was conducted based on the clinical data of patients with cerebrospinal fluid leakage after craniocerebral surgery who were admitted to the First People’s Hospital of Yichang from April 2016 to October 2020. The necrotic tissues were thoroughly removed. The dural defects were repaired with pedicled pericranial flaps, and soft tissue defects were repaired with local flaps. The incision was covered with negative pressure closed drainage dressing, and negative pressure was maintained at -50 to -80 mmHg (1 mmHg=0.133 kPa). Cerebrospinal fluid leakage, defect repair, and related complications were observed in postoperative follow-up.Results:A total of five patients (three males and two females, aged 49-65 years) were included. All patients had postoperative composite tissue defects with local infection after craniocerebral surgery, lasting two months to 12 years. The size of the postoperative dural defect ranged from 1.5 cm × 2.0 cm to 2.5 cm × 3.0 cm. The size of the scalp soft tissue defect ranged from 2.0 cm × 2.0 cm to 3.0 cm × 6.0 cm. The size of the pericranial flap ranged from 2.0 cm × 3.0 cm to 3.0 cm × 3.5 cm, and the local flap ranged from 8.0 cm × 13.0 cm to 12.0 cm × 16.0 cm. The cerebrospinal fluid leakage was still observed in one patient at 5 d after the surgery and was treated with continuous lumbar pool puncture for cerebrospinal fluid drainage, which healed one week later. One patient suffered from poor healing of the flap incision, which healed after two weeks of outpatient dressing changing. At the postoperative follow-up of 3 to 17 months, none had any further cerebrospinal fluid leakage, and no other complications such as intracranial infection, loss of frontal lines, scalp numbness, and necrosis occurred.Conclusions:Repair of dural defects by pedicled pericranial flaps can treat chronic cerebrospinal fluid leakage with less damage to the donor site and fewer complications.

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