OBJECTIVETo investigate the clinical features of thyroid disease occurring in response to antiviral therapy in patients with chronic hepatitis C (CHC).

METHODSEighty-two patients diagnosed with CHC were recruited for study from our hospital between 2009 and 2010. All patients were given a 48-week course of antiviral combination therapy with pegylated-interferon (Peg-IFN; 180 mug qw ih) and ribavirin (RBV; 15 mg/kg bw). Patient sera was collected prior to treatment (baseline), at treatment weeks 24 and 48, and post-treatment week 24, and used to detect changes in levels of thyroid function markers, thyroid-specific and other autoantibodies, complement factors, and immunoglobulins (Igs). Differential expression of biomarkers was assessed between patients who developed thyroid disorder and those who did not.

RESULTSAt treatment week 48, 13.4% (11/82) of cases developed hypothyroidism, 3.7% (3/82) developed hyperthyroidism, 20.7% (17/82) tested positive for thyroglobulin antibody, and 22.0% (18/82) tested positive for thyroid peroxidase antibody. The patients who did not develop thyroid disease had significantly higher post-treatment levels (vs. baseline) of IgG (14.84 +/- 2.61 vs. 12.95 +/- 3.32 g/L, F = 10.458, P = 0.002) and C4 (0.26 +/- 0.09 vs. 0.22 +/- 0.08 g/L, F = 6.835, P = 0.011) and significantly lower IgM (0.86 +/- 0.48 vs. 1.00 +/- 0.42 g/L, F = 9.106, P = 0.003). The patients who developed thyroid disease showed no significant differences in the baseline and post-treatment levels of IgG, C4, or IgM. When the two groups of patients who did or did not develop thyroid disease were compared, there was no difference in the amount of patients who achieved sustained virological response.

CONCLUSIONAntiviral-induced thyroid disease in patients with refractory hepatitis C manifests as clinically-detectable abnormalities in serum levels of thyroid autoantibody and markers of hypothyroidism. Levels of other autoantibodies and Igs do not correlate with the development of thyroid disease in these patients, and thyroid disease does not appear to affect the efficacy of Peg-IFN + RBV antiviral therapy.

Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Polyethylene Glycols ; therapeutic use ; Ribavirin ; therapeutic use ; Thyroid Diseases ; chemically induced

OBJECTIVETo investigate whether the -344T/C polymorphism of aldosterone synthase gene is associated with early renal damage in Han nationality with essential hypertension in Shandong province.

METHODSPlasma aldosterone concentration and urinary albumin excretion were measured with radioimmunoassays in 225 patients with essential hypertension, and hypertensives were classified as hypertension with normal albuminuria or hypertension with microalbuminuria according to urinary albumin excretion during 24 hours. -344T/C polymorphism of aldosterone synthase gene was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in controls and hypertensives.

RESULTSNo significant differences were found in genotype distribution among groups of control, primary hypertension with normal albuminuria and hypertension with microalbuminuria. The C allele frequency in hypertension with microal buminuria group was significantly higher than that in control and hypertension with normal albuminuria group (P < 0.05). In hypertensive patients, plasma aldosterone concentration and urinary albumin excretion of TC+CC genotypes were significantly higher than that of TT genotype ( P< 0.05).

CONCLUSIONThese results suggest that -344T/C polymorphism of aldosterone synthase gene may be associated with early renal damage in Han nationality with essential hypertension, C allele may be a genetic factor susceptible to renal damage in hypertensives.

Adult ; Albumins ; metabolism ; Albuminuria ; blood ; genetics ; Aldosterone ; blood ; Asian Continental Ancestry Group ; genetics ; China ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Genotype ; Humans ; Hypertension ; blood ; complications ; Kidney Diseases ; complications ; ethnology ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; genetics ; Radioimmunoassay

Objective To explore the effects of magnesium sulfate in combination with astragalus membranaceus injection on the birth outcomes and expression of placenta tissue related gene of patients with gestational hypertension. Methods Seventy-six gestational hypertension patients were selected and randomly assigned to control group (n = 38) and treatment group (n = 38). The control group was given intravenous injection of 25％ magnesium sulfate (60 mL) once daily for 7 days,while the treatment group was give intravenous injection of astragalus (60 mL) on the basis of the control group once daily for 7 days. The changes of blood pressure,mean arterial pressure (MAP) and 24 h urine protein content of the two groups were compared. The placenta tissue of the two groups were collected after childbirth. Results After treatment,the total effective rates of the control group and the treatment group were86. 84％ (33/38) and 97. 37％ (37/38) ,respectively; the difference was statistically significant (P < 0. 05). There were significant differences between the control group and the treatment group in systolic blood pressure [(147. 21 ± 20. 01) mmHg vs (128. 46 ± 18. 43) mmHg],diastolic blood pressure [(90. 25 ± 15. 46) mmHg vs (73. 14 ± 14. 53) mmHg],MAP [(126. 76 ± 9. 65) mmHg vs (108. 15 ± 9. 57) mmHg] and the 24 h urine protein content [(2. 65 ±0. 87) g vs (1. 34 ±0. 79) g](P < 0. 05). Conclusion Magnesium sulfate combined with astragalus membranaceus injection can reduce the blood pressure of gestational hypertension patients,improve the pregnancy outcome; the action mechanism maybe related to the up-regulation of PLGF and MMP-9 protein expression of placenta tissue.

Objective To investigate the effect of puerarin on oxidative stress and immune status in placenta of preeclampsia (PE) rats. Methods Forty-five pregnant female SD rats were randomly divided into control group,model group and test group,15 rats in each group. The rats in model group and test group were subcutaneously injected with 100 mg·kg-1 of L-arginine methyl ester (L-NAME) once daily from Day 13-21 of gestation,the rats in control group were injected with the same amount of saline; and the rats in test group were intraperitoneally injected with 80 mg·kg-1 of puerarin solution once daily from Day 17-21 of gestation,control group and model group were injected with the same amount of 0. 9％ NaCl. The caudal arterial pressure and 24 h urinary protein content were measured at Day 10,16 and 21 of gestation,the oxidative stress indexes in rat placenta was detected by thibabituric acid method and Xanthine oxidase method,the cellular immune function was detected by flow cytometry,and the X-linked inhibitor of apoptosis protein (XIAP) expressionin of rat placenta trophoblasts was detected by Western blot. Results On Day 21 of gestation,there were significant differences between the model group and the control/test group in caudal arterial pressure [(136. 25 ± 5. 48) mm- Hg vs (119. 25 ± 4. 21) mmHg or (123. 52 ± 6. 45) mmHg],24 h-urinary protein contents [((11. 83 ± 0. 12) mg vs 6. 42 ± 0. 08) mg or (8. 58 ± 0. 12) mg],the content of MDA in placenta tissue [(4. 75 ± 0. 08) mmol·mg-1 vs(10. 69 ± 0. 07) mmol·mg-1,(8. 37 ± 0. 08) mmol·mg-1 ],the content of SOD [(93. 26 ± 4. 29) U·mg-1 vs(168. 97 ± 3. 42) U·mg-1 or (112. 63 ± 3. 48) U·mg-1 ],the ratio of CD4 +/CD8 + [(2. 61 ± 0. 56) vs(1. 46 ± 0. 05) or (1. 48 ± 0. 12) ] and the relative expression of XIAP protein in trophoblast [(0. 89 ± 0. 05) vs(0. 36 ± 0. 09) or (0. 41 ± 0. 11) ](all P < 0. 05). Conclusion Puerarin can inhibit the oxidative stress reaction and enhance the cellular immune function in the placenta of PE rats,and reduce the expression of XIAP protein in the placenta tissue trophoblasts to reduce the apoptosis of placenta trophoblasts.

In acute lung injury, two subsets of lung macrophages exist in the alveoli: tissue-resident alveolar macrophages (AMs) and monocyte-derived alveolar macrophages (MDMs).However, it is unclear whether these 2 subsets of macrophages have different functions and characteristics during the recovery phase. RNA-sequencing of AMs and MDMs from the recovery period of LPS-induced lung injury mice revealed their differences in proliferation, cell death, phagocytosis, inflammation and tissue repair. Using flow cytometry, we found that AMs showed a higher ability to proliferate, whereas MDMs expressed a larger amount of cell death. We also compared the ability of phagocytosing apoptotic cells and activating adaptive immunity and found that AMs have a stronger ability to phagocytose, while MDMs are the cells that activate lymphocytes during the resolving phase. By testing surface markers, we found that MDMs were more prone to the M1 phenotype, but expressed a higher level of pro-repairing genes. Finally, analysis of a publicly available set of single-cell RNA-sequencing data on bronchoalveolar lavage cells from patients with SARS-CoV-2 infection validated the double-sided role of MDMs. Blockade of inflammatory MDM recruitment using CCR2 −/− mice effectively attenuates lung injury. Therefore, AMs and MDMs exhibited large differences during recovery. AMs are long-lived M2-like tissue-resident macrophages that have a strong ability to proliferate and phagocytose. MDMs are a paradoxical group of macrophages that promote the repair of tissue damage despite being strongly pro-inflammatory early in infection, and they may undergo cell death as inflammation fades. Preventing the massive recruitment of inflammatory MDMs or promoting their transition to pro-repairing phenotype may be a new direction for the treatment of acute lung injury.

Objective: To observe the treatment response of a two-dose regimen of inotuzumab ozogamicin (inotuzumab), a monoclonal antibody targeting CD22, for patients with heavily treated relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), including those failed or relapsed after chimeric antigen receptor (CAR) -T-cell therapy. Methods: Pediatric and adult patients who received two doses of inotuzumab and who were evaluated after inotuzumab treatment were included. Antibody infusions were performed between March 2020 and September 2022. All patients expressed CD22 antigen as detected by flow cytometry (>80% leukemic cells displaying CD22) before treatment. For adults, the maximum dosage per administration was 1 mg (with a total of two administrations). For children, the maximum dosage per administration was 0.85 mg/m(2) (no more than 1 mg/dose; total of two administrations). The total dosage administered to each patient was less than the standard dosage of 1.8 mg/m(2). Results: Twenty-one patients with R/R B-ALL were included, including five children (<18 years old) and sixteen adults. Seventeen patients presented with 5.0% -99.0% leukemic blasts in the bone marrow/peripheral blood or with extramedullary disease, and four patients were minimal residual disease (MRD) -positive. Fourteen patients underwent both CD19 and CD22 CAR-T-cell therapy, four underwent CD19 CAR-T-cell therapy, and three underwent blinatumomab therapy. Eleven patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). After inotuzumab treatment, 14 of 21 patients (66.7% ) achieved a complete response (CR, one was MRD-positive CR), and all four MRD-positive patients turned MRD-negative. Four of six patients who failed recent CD22 CAR-T-cell therapy achieved a CR after subsequent inotuzumab treatment. Seven patients (33.3% ) demonstrated no response. Grade 1-3 hepatotoxicity occurred in five patients (23.8% ), one child with no response experienced hepatic veno-occlusive disease (HVOD) during salvage transplantation and recovered completely. Conclusion: For patients with heavily treated R/R B-ALL, including those who had undergone allo-HSCT and CD19/CD22 CAR-T-cell therapy, the two-dose regimen of inotuzumab resulted in a CR rate of 66.7%, and the frequency of hepatotoxicity and HVOD was low.
Adult ; Humans ; Child ; Adolescent ; Inotuzumab Ozogamicin ; Receptors, Chimeric Antigen ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Antibodies, Monoclonal ; Adaptor Proteins, Signal Transducing ; Antigens, CD19 ; Chemical and Drug Induced Liver Injury

Objective: To evaluate the efficiency of internal carotid artery (ICA) embolization technology in endoscopic salvage surgery for recurrent nasopharyngeal carcinoma (rNPC) invading the ICA. Methods: From January 2016 to March 2021, 83 patients with rNPC who invaded the ICA and underwent endoscopic extended nasopharyngectomy were retrospectively collected from the Eye & ENT Hospital in Fudan University, including 60 males and 23 females. The age of the patients ranged from 27 to 77 years. The standard of ICA invasion was that the distance from the lesion to the ICA on enhanced MRI was ≤ 1.8 mm. The clinical characteristics, ICA management strategy and survival prognosis of patients were analyzed, and the effectiveness of ICA embolization was evaluated. Kaplan-Meier method was used to calculate the survival rate and Log-rank test was used to compare the difference. Results: In 83 patients with rNPC, there were 13 patients with rT2, 38 patients with rT3, 32 patients with rT4, and 16 patients had lymph node metastasis. A total of 37 patients (44.6%) underwent ICA coil embolization before surgery, of which 2 cases underwent external carotid-middle cerebral artery artery bypass grafting and ICA embolization due to positive balloon occlusion test (BOT). Patients with positive surgical margin accounted for 24.1% (20/83). Among them, patients with rT4 and patients without ICA embolization had a higher positive rate of surgical margin (P value was 0.001, 0.043, respectively). The 3-year overall survival (OS) and progression free survival (PFS) rate of all patients was 46.5% and 26.7%, respectively. In addition, the 3-year OS and PFS of patients with ICA embolization was significantly higher than those without ICA embolization, respectively (69.1% vs 27.8%, P=0.003; 33.9% vs 18.9%, P=0.018). Only 2 patients (2/37, 5.4%) had cerebral infarction complications after coil embolization of the affected ICA due to negative BOT. Conclusion: Preoperative ICA embolization can be used to treat patients with rNPC invading the ICA, improve the total removal rate and survival rate of patients, which is an effective salvage treatment.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Nasopharyngeal Carcinoma ; Salvage Therapy ; Retrospective Studies ; Carotid Artery, Internal ; Neoplasm Recurrence, Local/surgery* ; Nasopharyngeal Neoplasms/pathology*

Objective: To evaluate the feasibility of the endoscopic transnasal approach (ETA) and to analyze the outcomes and factors of this surgical technique in the management of the tumor invading the anterior skull base. Methods: A retrospective analysis was performed on 42 patients (31 males and 11 females, with mean age of 49 years) with sinonasal tumor invading the anterior skull base, who underwent ETA from June 2015 to April 2019 in Eye, Ear, Nose and Throat Hospital of Fudan University. Pathologically, there were 15 cases of squamous carcinoma (14 patients with T4bN0M0 and 1 patient with T4bN1M0) and 27 of olfactory neuroblastomas with Kadish stage C. Anterior skull base reconstruction was performed using the vascular pedicled nasoseptal mucoperiosteal flap and fascia lata. Brain non-contrast-enhanced CT was performed on the first postoperative day to exclude massive pneumocephalus, relevant brain edema and subarachnoid hemorrhage. Sinonasal contrast-enhanced MR was performed to assess the extent of the tumor removal. Kaplan-Meier analysis was used to calculate the overall survival (OS) and Cox multivariate regression analysis was used to determine the prognostic factors. Results: The mean duration of the surgery was 452 minutes. Total resection was performed in 36 patients (85.7%), subtotal resection in 2 patients (4.8%) with orbital involvement, partial resection in one patient (2.4%) with injury of the internal carotid artery. One patient (2.4%) underwent the second resection because of the tumor residual, two patients (4.8%) with unsure tumor residual. Mean follow-up was 20 months, with 17 months of median follow-up. One-, two-and three-year overall survival was 86.5%, 76.9% and 64.5%, respectively. For squamous carcinoma, one-, two-and three-year overall survival was 86.2%, 86.2% and 57.4%, respectively. For olfactory neuroblastomas, One-, two-and three-year overall survival was 86.9%, 75.3% and 67.8%, respectively. Multivariate analysis showed that tumor residual (P=0.001) and recurrence (P<0.01) were independent prognostic factors for survival. Conclusions: The ETA is safe and feasible in selected patients with sinonasal tumor invading the anterior skull base. Tumor residual and recurrence are independent prognostic factors for survival.
Female ; Humans ; Male ; Middle Aged ; Nasal Cavity ; Neoplasm Recurrence, Local ; Nose Neoplasms/surgery* ; Retrospective Studies ; Skull Base/surgery* ; Skull Base Neoplasms/surgery*

Quality marker(Q-marker) is a new concept and pattern for quality control of traditional Chinese medicine(TCM),which will lead the development direction for quality control of TCM.Among them,how to characterize the overall quality attribute of TCM and its biological effect,is a critical scientific problem in the study of Q-marker.In this paper,integrated pharmacology is utilized to screen out and confirm the Q-marker from the complex system of TCM,so as to solve the critical scientific problem.System biology in vivo is firstly applied to establish the correlation of chemical fingerprints of TCM,their metabolic fingerprints,network targets,biological effects and efficacy of TCM,which is used to preliminary screen out Q-marker of TCM.Following that,a pharmacological method in vitro,including intestinal absorption in vitro coupled with bioactivity assessment,is employed to simultaneously determine the absorbed doses of TCM and evaluate their biological activity.Furthermore,data mining is utilized to establish the exact quantitative mathematic model between Q-marker of TCM and bioactivity.Meanwhile,two representative examples,including Yuanhu Zhitong tablets,Xinsuning capsules,are introduced to identify Q-marker of TCM and establish their quality standards related with bioactivity,which will be beneficial to improve the level of quality control of TCM and ensure the effectiveness and safety of clinical applications.