The abnormal accumulation of neutrophil extracellular traps （NETs） can promote the initiation and progression of pancreatic cancer， which is considered a potential therapeutic target for this disease. The Miraculous Pivot·Inquiry About Statement （《灵枢·口问》） have recorded the concept of "defensive qi stagnation". Based on the recognition that the function of defensive qi is similar to the immune function of neutrophils， and combining traditional Chinese medicine theory with clinical practice， it is proposed that the abnormal accumulation of NETs may be a pathological product of "defensive qi stagnation"， with the spleen being the critical site of pathology. Further exploring the application strategy of cleaning spleen and restoring defensive qi method in pancreatic cancer treatment， it is proposed to employ three approaches such as dredging method to eliminate spleen stagnation and inhibit pancreatic cancer proliferation， cleaning method to remove spleen dampness and suppress the inflammatory micro-environment， and tonifying method to strengthen Weiqi and to improve the immune microenvironment， which aims to provide new insights for the clinical treatment of pancreatic cancer with traditional Chinese medicine.

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

Objective To retrospectively analyze the ultra-fast track anesthesia(UFTA)methods and perioperative anesthesia management experiences of transcatheter mitral valve edge-to-edge repair(TEER)in the treatment of functional mitral regurgitant.Methods In this retrospective study,patients underwent the TEER procedure and received UFTA in Fuwai Yunnan Hospital,from May 2022 to September 2022 for heart failure combined with moderate to severe or severe functional mitral regurgitant were included.Baseline,preoperative complications,cardial function and anesthesia classification,amino-terminal probrain natriuretic peptide(NT-proBNP),ultrasound examination results,surgery time,extubation time,intraoperative anesthetic and vasoactive drug,complications related to TEER and UFTA,perioperative,and postoperative 30-day and one-year follow-up data were collected.All perioperative clinical data were recorded and analyzed.Results A total of 30 patients were enrolled,11 patients(36.7％)were female,mean age was(63.6±6.1)years,NYHA classification IV 14 patients(46.7％),left ventricular ejection fraction(LVEF)(36.0±8.1)％,the end-diastolic volume of the left ventricle(66.0±8.2)mm,mitral regurgitation 4+14 patients(56.7％),3+17 patients(43.3％),NT-proBNP(1 934.1±1 973.5)pg/ml,1 patient(3.3％)used high-dose vasoactive drugs during surgery.All patients did not experience nausea,vomiting,delirium,respiratory depression,perioperative transesophageal echocardiography-related gastrointestinal bleeding,pericardial effusion,cerebrovascular accidents,emergency surgery or secondary intervention,or other serious adverse events within 24 hours after surgery.No 30-day all-cause death occurred;the mean postoperative hospital stay was(7.4±2.8)days.All patients completed one-year follow-up,LVEF(37.6±11.1)％,the end-diastolic volume of the left ventricle(63.2±8.6)mm,mitral regurgitation 2+7 patients(23.3％),1+23 patients(76.7％),NT-proBNP(1 949.2±2 576.6)pg/ml.Conclusions Ultra-fast track anesthesia can be safely applied to TEER in treating functional mitral regurgitant patients.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

OBJECTIVE: Androgen deficiency is common in aging males and may have unfavourable health consequences. Large-scale studies suggested low testosterone level might increse mortality and morbidity in ageing males. However, young men with low testosterone level might be neglected. Recent studies reported young men with infertility may have reduced testosterone level. To investigate the incidence of androgen deficiency in males with infertility and possible factors affecting the low testosterone level. METHODS: Between January 2011 and December 2012, 407 men with infertility caused by varicocele (VC), obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) in our center were included. The number of men in each group of OA, NOA and VC was 141, 97 and 169, respectively. All the eligible patients underwent a serum testosterone assessment by a single morning blood draw (between 8:00 to noon) to test for concentration of the total testosterone. All serum samples were determined by radioimmunoassay in our andrology laboratory. Androgen deficiency was defined as having a total testosterone level less than 300 ng/dL. RESULTS: The mean age was (30.4±5.8) years. The mean testosterone level was (4.18±1.64) ng/dL (range 0.30 to 11.32 ng/dL). The overall incidence of androgen deficiency was 26.5% (108/407). The incidences of androgen deficiency in NOA, OA and VC groups were 40.2% (39/97), 19.1% (27/141) and 24.9% (42/169), respectively, which were significantly higher in the NOA than in the VC and OA groups (P < 0.001). The incidences had no difference between the VC and OA groups (P=0.229). Univariate analysis revealed the cause of infertility, FSH and the mean testis volume as possible affecting factors for androgen deficiency. However, on multivariate analysis the only cause of infertility was an independent predictor. The incidence of androgen deficiency was the highest in the NOA group [OR 0.492 (95% confidence interval 0.288-0.840)]. CONCLUSION NOA and varicocele might be risk factors of androgen deficiency. Young men with NOA may have a higher possibility of low testosterone level. Testosterone level should be followed up after NOA and varicocele treatment. Androgen deficiency should be assessed in males with infertility in clinical practice.
Adult ; Androgens ; Azoospermia/etiology* ; Female ; Humans ; Male ; Testis ; Testosterone ; Varicocele/complications* ; Young Adult

Objective: To compare and correlate the findings of intravoxel incoherent motion (IVIM) magnetic resonance (MR) imaging and arterial spin labeling (ASL) imaging in characterizing parotid gland tumors. Materials and Methods: We retrospectively reviewed 56 patients with parotid gland tumors evaluated by MR imaging. The true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and fraction of perfusion (f) values of IVIM imaging and tumor-to-parotid gland signal intensity ratio (SIR) on ASL imaging were calculated. Spearman rank correlation coefficient, chi-squared, Mann-Whitney U, and Kruskal-Wallis tests with the post-hoc Dunn-Bonferroni method and receiver operating characteristic curve assessments were used for statistical analysis. Results: Malignant parotid gland tumors showed significantly lower D than benign tumors (p = 0.019). Within subgroup analyses, pleomorphic adenomas (PAs) showed significantly higher D than malignant tumors (MTs) and Warthin’s tumors (WTs) (p < 0.001). The D* of WTs was significantly higher than that of PAs (p = 0.031). The f and SIR on ASL imaging of WTs were significantly higher than those of MTs and PAs (p < 0.05). Significantly positive correlation was found between SIR on ASL imaging and f (r = 0.446, p = 0.001). In comparison with f, SIR on ASL imaging showed a higher area under curve (0.853 vs. 0.891) in discriminating MTs from WTs, although the difference was not significant (p = 0.720). Conclusion IVIM and ASL imaging could help differentiate parotid gland tumors. SIR on ASL imaging showed a significantly positive correlation with f. ASL imaging might hold potential to improve the ability to discriminate MTs from WTs.

OBJECTIVE: To assess clinical value of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for differentiation of malignant from benign focal thyroid incidentaloma. MATERIALS AND METHODS: This retrospective study included 99 patients with focal thyroid incidentaloma of 5216 non-thyroid cancer patients that had undergone PET/CT. PET/CT semi-quantitative parameters, volume-based functional parameters, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of thyroid incidentaloma were assessed. Receiver-operating characteristic (ROC) analysis was conducted and areas under the curve (AUC) were compared by Hanley and McNeil test to evaluate usefulness of maximum standardized uptake value (SUVmax), MTV and TLG, as markers for differentiating malignant from benign thyroid incidentalomas. RESULTS: Of 99 thyroid incidentalomas, 64 (64.6%) were malignant and 35 (35.4%) were benign. Malignant thyroid incidentalomas were larger (1.8 cm vs. 1.3 cm, p = 0.006), and had higher SUVmax (11.3 vs. 4.8, p < 0.001), MTV (all p < 0.001) and TLG (all p < 0.001) than benign. TLG 4.0 had the highest performance for differentiation of malignant from benign thyroid incidentaloma in all semi-quantitative parameters with AUC 0.895 by ROC curve analysis. AUC (TLG 4.0) was significantly larger than AUC (SUVmean), AUC (MTV 2.5), AUC (MTV 3.0), AUC (MTV 3.5), AUC (TLG 2.5), and AUC (TLG 3.0), respectively (all, p < 0.05). There was no statistical difference between AUC (TLG 4.0) and AUC (SUVmax) (p > 0.05). A threshold TLG 4.0 of 2.475 had 81.3% sensitivity and 94.3% specificity for identifying malignant thyroid incidentalomas. CONCLUSION: Volume-based PET/CT parameters could potentially have clinical value in differential diagnosis of thyroid incidentaloma along with SUVmax.
Area Under Curve ; Diagnosis, Differential ; Electrons ; Fluorodeoxyglucose F18* ; Glycolysis ; Humans ; Positron-Emission Tomography and Computed Tomography* ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Thyroid Gland* ; Thyroid Neoplasms ; Tumor Burden

Objective To introduce an optimized practical method of making and detecting pipettes for microinjection.Methods Transfer pipette was made from hard glass capillary. We softened the hard glass capillary by rotating it in a spirit-lamp flame,then moved out from the flame and quickly pulled it into two transfer pipettes.After broken by a grinding wheel,the tip of the pipette was fire-polished by quickly touching the flame to make a fine opening.A hard glass capillary (1.0 mm,ouside diametre)was pulled into two holding pipettes by pipette Puller.The pipette shoulder was broken at desired position with a grinding wheel,then the fine pipette tip opening was heated by a microforge and shrinked into a diameter -15 μm.Injection pipette could be made directly from a capillary with filament by Puller.The solution loaded injection pipette and holding pipette were assembled into the micromanipulator and could be checked before use.We transfered both pipettes into the zygotes media drop,touched the holding pipette with the tip of the injection pipette to make a "suitable"opening.Then we switched injection pipette to the mineral oil and applied injection pressure through the injector to check whether the solution could come out of the tip smoothly and at a proper speed.It could be further verified by pronucleus microinjection of zygotes.Results The results showed that the method introduced in this paper could produce suitable pipettes for zygote microinjection.In particular,the method of detecting the opening of the injection pipette was helpful for achieving high efficiency of zygote microinjection.Conclusion The method introduced here to make and detect pipettes for microinjection is very helpful for establishing a standard microinjection manipulation procedure and improving the efficiency of zygote microinjection.

Tanreqing injection (TRQ), a well-known traditional Chinese medicine formula, is commonly used to treat respiratory diseases. In the present study, a rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determinate the plasma contents of 5 major constituents of TRQ, including chlorogenic acid (CHA), caffeic acid (CFA), baicalin (BA), ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in rats after intravenous administration of TRQ. Chromatographic separation was performed on an Agilent Zorbax SB-C column (3.5 μm, 100 mm × 2.1 mm), with acetonitrile and 0.1% aqueous formic acid as mobile phase at a flow rate of 0.3 mL·min. The calibration curves were linear over the ranges of 27.0-13 333.0 ng·mL for CFA, 30.0-14 933.0 ng·mL for CHA, 50.0-50 333.0 ng·mL for BA, 550.0-55 000.0 ng·mL for UDCA, and 480.0-48 000.0 ng·mL for CDCA, respectively. Intra- and inter-day precisions (relative standard deviations, RSDs) were from 3.11% to 14.08%. The extraction recoveries were greater than 71% and accuracy (relative recovery) was from 89% to 137% for all analytes, except endogenous bile acids. This validated method was successfully applied to the first pharmacokinetic study of CFA, CHA, BA, UDCA and CDCA in rat plasma after intravenous administration of TRQ.
Animals ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; pharmacokinetics ; Male ; Molecular Structure ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; methods

Objective To discuss the value of diffusion-weighted MRI (DWI) and 18F-FDG-PET/CT in assessing the early therapeutic effect of radiofrequency ablation (RFA) for VX2 sarcomas in experimental rabbits. Methods VX2 sarcoma was inoculated at bilateral hind limbs in 14 New Zealand white rabbits to establish the animal models. The implanted VX2 tumor on one hind leg was treated with ultrasound-guided percutaneous RFA (study group), while no RFA was given to the VX2 tumor on the contralateral hind leg (control group). DWI-MRI was performed at 2 days after RFA, and 18F-FDG-PET/CT examination was employed at 3 days after RFA. The mean apparent diffusion coefficient (ADC) values and standard uptake value (SUV) of the untreated tumor and the ablated tumor were separately calculated. Taking the pathologic result as the gold standard, the consistency of DWI-MRI, PET/CT as well as the combination of DWI-MRI and PET/CT with the clinical diagnosis was separately evaluated by Kappa test. Results Before RFA, DWI-MRI demonstrated that the VX2 tumor was characterized by hypo-intensity signal on T1 and hyper-intensity signal on T2 with ring-shaped enhancement on T1-weighted image; PET/CT showed that the tumor had nodular or ring-shaped 18F-FDG accumulation. After RFA, DWI-MRI revealed that the VX2 tumor was manifested as hyper-intensity signal on T1 and slight higher density on T1 with slight enhancement on contrast-enhanced T1-weighted image; PET/CT showed lowered accumulation of 18F-FDG. The mean ADC value of the ablated tumor was (1.52 ± 0.24) × 10-3 mm2/s, which was obviously higher than that of the un-ablated tumor, that was (1.09 ± 0.12) × 10-3 mm2/s, the difference was statistically significant(P<0.05). The mean SUV value of the ablated tumor was (0.6 ± 0.3), which was significantly lower than that of the ablated tumor (9.6 ± 3.2, P<0.05). No significant difference in sensitivity, specificity and accuracy existed between DWI-MRI and pathology as well as between PET/CT and pathology, the Kappa value being 0.357 and 0.428 respectively (P>0.05). The Kappa value of the consistency between combination of DWI-MRI with PET/CT and pathology was 0.786, which was significantly different from the result by simple DWI-MRI or simple PET/CT evaluation (P< 0.05). Conclusion Both ADC value of DWI-MRI and SUV value of PET/CT are useful indexes for evaluating the early therapeutic effect of RFA. Both DWI-MRI and PET/CT have their respective advantages, nevertheless, combination use of both can effectively improve the evaluation of curative effect for VX2 tumor after RFA in experimental rabbits.