Objective To establish high performance liquid chromatography(HPLC)characteristic chromatograms of Xinqingduyin Granules(composed of Taraxaci Herba,Lonicerae Japonicae Flos,Chrysanthemi Indici Flos,etc.)and content determination of chicory acid and glycyrrhizic acid,and to optimize the preparation process of Xinqingduyin Granules.Methods Using the characteristic chromatograms of Xinqingduyin and the retention rate of chicory acid and glycyrrhizic acid as indexes,we carried out orthogonal experiment to optimize the extraction process of Xinqingduyin,and studied the concentration process.The molding process of Xinqingduyin Granules was conducted by screening the types and dosage of auxiliary materials,then three batches of pilot experiments were carried out.Results HPLC characteristic chromatograms of Xinqingshuyin Granules and the determination methods of chicory acid and glycyrrhizic acid were established.The optimal preparation technology was as follows:8 times amount of water was added,the drug was decocted for 3 times,with 1 hour per time.After the extract was concentrated under reduced pressure at 80℃,the appropriate amount of steviol glycoside and lactose was added into the extract and mixed.One-step granulation and packaging were adopted.The retention rates of chicoric acid and glycyrrhizic acid in the 3 batches of Xinqingduyin Granules,which were prepared on the pilot scale,were(54.56±1.63)%and(54.96±1.08)%,and the rate of finished product was(87.47±0.49)%,respectively.The quality is uniform,and the characteristic map of Xinqingduyin Granules showed high similarity with that of decoction prepared from the same batch of slices.Conclusion The optimized preparation technology is reasonable,feasible and reproducible.This preparation can be used to obtain the granule with similar materials of Xinqingduyin decoction.

Objective To establish a HPLC method for the simultaneous determination of artemisinin,arteannuin B,chrysosplenetin and chrysosplenol-D in the water extract of Artemisia annua L.Methods The analysis was performed on Agilent ZORBAX SB-C18(250 mm×4.6 mm,5 μm)column with a mobile phase of acetonitrile(A)-water(B)and the flow rate of 0.8 mL·min-1 in a gradient elution manner.The column temperature was 30℃.The injection volume was 10 μL,and the detection wavelength was 210 nm.Results Artemisinin,arteannuin B,chrysosplenetin and chrysosplenol-D were correlated well linearly with peak area in their respective ranges 1.608 8-16.088 μg(r=0.999 9),0.014 1-0.141 4 μg(r=1),0.185 1-1.850 9 μg(r=0.999 9),0.144 1-1.441 4 μg(r=0.999 9),the average recovery rate(n=6)were 102.44%,97.82%,95.07%,95.55%,and the RSD values were 1.12%,1.44%,1.29%,1.53%.Conclusion This method is convenient and accurate.It has good stability and repeatability,and can be used to simultaneously determine the content of artemisinin,arteannuin B,chrysosplenetin and chrysosplenol-D in the water extract of Artemisia annua L.

Extracellular vesicles (EVs) are phospholipid bilayer vesicles actively secreted by cells, that contain a variety of functional nucleic acids, proteins, and lipids, and are important mediums of intercellular communication. Based on their natural properties, EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers. Among them, plant-derived nanovesicles (PNVs) are characterized as natural disease therapeutics with many advantages such as simplicity, safety, eco-friendliness, low cost, and low toxicity due to their abundant resources, large yield, and low risk of immunogenicity in vivo. This review systematically introduces the biogenesis, isolation methods, physical characterization, and components of PNVs, and describes their administration and cellular uptake as therapeutic agents. We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, wound healing, regeneration, and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19. Finally, the toxicity and immunogenicity, the current clinical application, and the possible challenges in the future development of PNVs were analyzed. We expect the functions of PNVs to be further explored to promote clinical translation, thereby facilitating the development of a new framework for the treatment of human diseases.

Objective:To explore the categories and influencing factors of family caregivers′benefit finding in patients with esophageal cancer based on latent profile analysis.Methods:From May 2020 to February 2021, 255 primary family caregivers of patients with esophageal cancer in the First People′s Hospital of Changzhou and Affiliated Hospital of Jiangnan University were selected for the study using a cross-sectional survey method. Surveys were conducted by the General Information Questionnaire, the Benefit finding Scale, the Hospital Anxiety and Depression Scale, and the Event Related Rumination Inventory.Results:The benefit finding among family caregivers of patients with esophageal cancer was divided into 2 latent profile classifications, low benefit rumination group 33.3% (85/255) and high growth adaptation group 66.7% (170/255), and the results of binary Logistic regression analysis showed that caregivers with high school education or above ( OR=0.053, P<0.05) and higher deliberate rumination scores ( OR=0.778, P<0.01) had a higher degree of benefit finding; caregivers with higher intrusive rumination scores ( OR=1.163, P<0.05) and higher anxiety ( OR=1.323, P<0.01) and depression scores ( OR=1.128, P<0.05) had a lower benefit finding. Conclusions:There is heterogeneity in the caregiver′s benefit finding of patients with esophageal cancer. Health professionals and nursing staff should develop targeted psychological support and interventions to improve the caregiver ′s benefit finding according to the different sub-types of caregivers.

Objective To prepare berberine hydrochloride nanoemulsion, optimize its formulation composition and preparation process, and investigate its in vitro characteristics. Methods BBR-NE was prepared by water drop addition and pseudo-ternary phase diagram was drawn. The formulation of NE was optimized by central composite design-response surface methodology to choose the optimal formulation composition. The particle size, potential and appearance of the prepared BBR-NE were characterized. Results The optimal prescription of BBR-NE was determined as the oil phase Capryol 90 accounted for 32.84% of the system, the surfactant Tween-80 accounted for 33.90%, the co-surfactant 1,2-propylene glycol accounted for 16.95%, and water relative system accounted for 15.25%. The prepared NE was clear and transparent in appearance, regular in shape and uniform in size, with an average particle diameter of (68.85±8) nm, polydiseperse index of (0.245±0.03) and drug loading of 0.83 mg/g. The in vitro drug release results of NE showed that the in vitro drug release behavior was passive diffusion, which had a certain slow releasing effect and met the first-order release equation. Conclusion The BBR-NE can provide a new dosage form for the clinical use of berberine.

Objective Colon-targeting capsules based on gastric pellets and enteric pellets were prepared from Baizhu Huanglian prescription. The formulation composition and preparation process were optimized and the in-vitro release characteristics were investigated. Methods Optimum formulation composition and process parameters of Baizhu Huanglian pellets were screened out by single factor experiment and orthogonal design. The pellets core were prepared by extrusion-spheronization technique and coated in the fluid bed using bottom spray coating technique. To investigate the effect of coating level of the isolation layer, the proportion of polymer, the amount of plasticizer and weight gain of enteric coating on the release behavior of the enteric pellets. The pellets release behavior was fitted by model as well. Results The prescription of gastric pellets was drug loading 50%, PVPP 5%, MCC to lactose 1∶2 and wetting agent 40%. The process parameters were extrusion frequency 20 Hz, rounding speed 500 r/min and rounding time 5 min. The prescription of enteric pellets was drug loading 27%, PVPP 5%, MCC to lactose 5∶2, wetting agent 30% and adhesive 20%. The process parameters were extrusion frequency 20 Hz, rounding speed 700 r/min and rounding time 7 min. For enteric coating layer, the coating mixture of EUDRAGIT®L30D-55 to EUDRAGIT® FS30D was 1∶2. The amount of plasticizer was 10%. The increased weight of coating layer was 15%. The release time of enteric pellets in-vitro was up to 24 hours. The release behavior of the pellets conforms to the Higuchi model. Conclusion The colon targeting capsule of Baizhu Huanglian pellets were successfully prepared and showed the characteristics of sustained release and colon targeting.

This article reported a case of malignant pheochromocytoma and paraganglioma with cranial metastasis. The patient was a 25-year-old man. At the age of 10, he was diagnosed with retroperitoneal paraganglioma. He received radiotherapy after partial resection of the tumor. At the age of 15, when he consulted for headache and hypertension, a space occupying lesion was found on the right adrenal without further diagnosis and treatment. His headache and hypertension were aggravated at the age of 25. Then he visited our medical center and diagnosed with right adrenal pheochromocytoma. He undertook an operation to remove the right adrenal lesion, and his blood pressured could be controlled in the normal range with oral antihypertensive medication. One year after the surgery, a cranial lesion with positive 131I-metaiodobenzylguanidine imaging was found following the increase of norepinephrine and dopamine in both blood and urine. The diagnosis of malignant pheochromocytoma with cranial metastasis was confirmed. The cranial lesion was treated with cyberknife therapy for 4 times, and the lesion was slightly reduced. Four year after the removal of right adrenal tumor, he developed multiple bone metastasis in the right ribs and left ilium, and then he received 131I-metaiodobenzylguanidine radiotherapy. Additionally, the results of gene test indicated a pathogenic mutation of SDHB. During the follow-up period of one year after the treatment, his blood pressure fluctuated to about 140/90mmHg with 10mg of phenoxybenzamine once a day. The case is a malignant pheochromocytoma with multiple bone metastasis characterized by a long course with an ideal prognosis in a way. Consequently, we suggested the diagnostic pathway with genetic testing based on clinical phenotype to approach more timely diagnosis and reasonable evaluation of the prognosis in pheochromocytoma and paraganglioma. Furthermore, clinicians should pay more attention to the long-term surveillance.

Objective To explore the potential influence of gender on screening value of aldosterone-renin ratio (ARR) for primary aldosteronism (PA).Methods The biochemical parameters were collected of 451 PA patients and 300 essential hypertension (EH) patients who were diagnosed in the General Hospital of PLA from 1992 to 2014. Each group was then divided into two groups by gender. The clinical characteristics were compared and then the receiver operating characteristic curve (ROC) was conducted to evaluate the best cut-off value.Results The plasma aldosterone concentration (PAC), serum sodium and ARR were much higher, but the plasma rennin activity (PRA), serum potassium and BMI were much lower in PA patients than in EH patients (P<0.01), and no significant difference existed between the two groups in age, duration of hypertension and blood pressure. The PRA was obviously lower in males than in females either in PA or in EH patients, but no signicantcant difference existed between males and females in PAC (P>0.05). The best cut-off value of ARR in male PA patients was 19.11, the relevant area under the curve (AUC) was 0.968, the sensitivity and specicantcity was 92.44% and 93.08%, and the Youden index (YI) was 0.86. The best cut-off value of ARR in female PA patients was 27.26, with AUC 0.956, sensitivity 92.07%, specicantcity 90.00% and YI 0.82, respectively. If the cut-off value was set at 27.26 in males, the specicantcity would rise a little, but the sensitivity and YI would sharply decrease. Similarly, the sensitivity would increase a little but the specicantcity and YI would fall substantially if the cut-off value in females was set at 19.11. The best cut-off value of ARR in men was smaller than the ocantcial value recommended by guidelines.Conclusion Gender is an important factor should be considered while ARR is used in PA screening, and the cut-off value of ARR in screening female PA patients should be setting higher.

Objective To investigate the correlation between body mass index (BMI) and the occurence of papillary thyroid carcinoma (PTC) among the patients with thyroid nodules. Methods This cross-sectional study collected the data of 4 350 patients with thyroid nodules who underwent thyroidectomy in our hospital from January 1994 to December 2013. The patients were divided into normal weight (BMI 18.50~23.9 kg/m 2), overweight (BMI 24.0~27.9 kg/m 2), and obese (BMI≥28.0 kg/m 2) groups according to BMI, as well as benign nodules and papillary thyroid carcinoma groups based on their pathological finding. The differences of age-sex composition, nodule diameter, TSH level, overweight and obese constituent ratio between two groups were also analyzed. Logistic regression method was used to evaluate the risk factors of PTC. Results (1) Compared with the benign nodule group, there was a higher proportion of patients under the age of 40 years (34.1% vs 19.5%, P<0.01) in PTC group, with smaller tumour diameters [ 1.0 (0.7-2.0) cm vs 3.0 (2.0-4.0) cm, P<0.01]and higher TSH levels [ 1.9 (1.2-3.0) mU/L vs 1.6 (0.9-2.5) mU/L, P<0.01]. (2) The proportion of obese patients was higher in PTC group than that in the benign nodule group (28.7% vs 20.7%, P<0.01) among male patients. While the difference was not found among female patients. (3) Stratification analysis according to gender and age showed that the proportion of overweight (49.4% vs 44.1%, P<0.05) or obese (26.5% vs 15.3%, P<0.01) in PTC group was higher than that of benign nodule group among male patients aged≤40 years and the proportion of obese patients in PTC group was higher than that of benign nodule group (30.8% vs 22.2%, P<0.01) among male patient aged 41 to 65 years. (4) A multivariate analysis indicated that overweight (OR=4.947) and obesity (OR=7.648) were all independent risk factors for PTC (P<0.01) among male patients aged≤40 years. Conclusion Overweight and obesity are associated with higher PTC risk for male patients aged 40 years or less.

Objective To investigate the trends in the clinicopathological characteristics of thyroid cancer patients undergoing surgery from 1994 to 2013. Methods A retrospective analysis was conducted on the clinical data of inpatients with thyroid nodular diasease undergoing thyroidectomy with pathology results from January 1994 to December 2013. The trends in the pathogenic constituent of thyroid nodule and the clinicopathological characteristics of 3 399 patients with thyroid cancer were analyzed. Results (1) Over the past 20 years, the proportion of patients diagnosed as thyroid cancer was gradually increased, especially those with papillary thyroid cancer (PTC). Whereas the proportions of benign nodule and other rare thyroid cancer were gradually decreased(P<0.01). (2) The average age of patients with thyroid cancer was (44.30±11.72) years, with the peak incidence at 30~59 years. The incidence of thyroid cancer was increasing in both males and females, especially more evident in the absolute increase in women(P<0.05). (3) Among 3 399 patients with thyroid cancer, 56.20%(1 910/3 399)underwent subtotal lobectomy. 20.74%(705/3 399)underwent total/near total thyroidectomy, showing an increase trend (P<0.01). Ultrasound-guided aspiration biopsy for thyroid nodule were performed in 48.87% (1 661/3 399)patients before operation. The proportion of aspiration biopsy was gradually increased since 2004. (4) An increase in thyroid cancer of tumor sizes less than 2.0 cm was observed, especially those size≤1.0 cm(P<0.01). 83.96%(2 854/3 399)patients revealed TNM Ⅰ~Ⅱ stage, and the proportion of patients with TNM Ⅲ~Ⅳ stage was gradually decreased since 2006(P<0.01). Conclusion Over the past 20 years, the proportion of thyroid cancer, especially papillary thyroid microcarcinoma reveals an ascending tendency. The percentages of patients undertaking total/near total thyroidectomy and ultrasound-guided aspiration biopsy before operation are on the rising.