Objective:To discuss the regulatory effect of berberine(BBR)on fatty acids in the human glioma T98G cells and its effect on the cell proliferation,migration,and invasion,and to clarify its potential mechanism.Methods:The T98G cells at logarithmic growth phase were divided into control group and different concentrations(25,50,and 100 mg·L-1)of BBR groups.Cell wound healing assay was used to detect the migration rates of the cells in various groups;Transwell chamber assay was used to detect the invasion rates of the cells in various groups.The T98G cells at logarithmic growth phase were divided into control group and 100 mg·L-1 BBR group,and Mass spectrometry was used to detect the fatty acid contents in the cells in two groups.The T98G cells at logarithmic growth phase were divided into control group and different concentrations(50,100,and 150 mg·L-1)of BBR groups;Western blotting method was used to detect the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(AKT),phosphorylated AKT(p-AKT),sterol regulatory element-binding protein 1(SREBP-1),and fatty acid synthase(FASN)in the cells in various groups.The expression of FASN was suppressed by gene silencing technology,and the T98G cells at logarithmic growth phase were divided into control group,shFASN1 group,and shFASN2 group.Western blotting method was used to detect the expression levels of FASN protein in the cells in various groups;clone formation assay was used to detect the clone formation of the cells in various groups;cell wound healing assay was used to detect the migration rates of the cells in various groups.Results:Compared with control group,the migration rates and invasion rates of the cells in different concentrations of BBR groups were decreased in a concentration-dependent manner(P<0.01),and the fatty acid content in the cells in 100 mg·L-1 BBR group was significantly decreased(P<0.01).Compared with control group,the expression levels of p-PI3K,p-AKT,SREBP-1,and FASN proteins in the cells in 150 mg·L-1 BBR group were significantly decreased(P<0.05 or P<0.01),and the expression level of SREBP-1 protein in the cells in 100 and 150 mg·L-1 BBR groups were significantly decreased(P<0.01).After suppression of FASN expression,compared with control group,the expression levels of FASN protein in the cells in shFASN1 and shFASN2 groups were significantly decreased(P<0.01),and the expression level of FASN protein in the cells in shFASN2 group was lower than that in shFASN1 group(P<0.05);compared with control group,the numbers of clone formation and migration rates of the cells in shFASN1 and shFASN2 groups were significantly decreased(P<0.01),and the migration rate of the cells in shFASN2 group was significantly lower than that in shFASN1 group(P<0.05).Conclusion:BBR interferes with fatty acid synthesis in the glioma T98G cells by reducing the expression of the PI3K/AKT/SREBP-1/FASN pathway related proteins,and decrease their migration and invasion capabilities.

There are a total of 16 couplet medicines of Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma in the book FU Qingzhu Nüke, covering a wide range of diseases such as leukorrheal diseases, menopathy, pregnancy, and puerperal diseases, and there is a fine sense of the dosage, processing, and proportion of the couplet medicines. Through analyzing the cases of Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma couplet medicines and the characteristics of dosage, processing, and proportion, we conclude that Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma couplet medicines are mainly as followed: smoothing liver and strengthening spleen in treating leukorrheal diseases to remove dampness and stop leucorrhoea; regulating liver and tonifying spleen in menopathy to regulate menstruation and relieve pain; nourishing blood and benefiting qi in pregnancy to lower adverse qi and tranquilize fetus to prevent miscarriage; regulating and tonifying qi and blood in puerperal diseases to eliminate pathogenic factors and promote lactation; suppressing hyperactive liver for descending adverse qi, and relieving spasm and pain in cases of miscarriage due to rage. In terms of dosage, Paeoniae Radix Alba is mainly used for three to five qian, and Glycyrrhizae Radix et Rhizoma is primarily used for one qian, and the dosage of the two medicinals is adjusted according to the degree of primary and secondary liver stagnation and spleen deficiency. In terms of processing, wine Paeoniae Radix Alba and raw Glycyrrhizae Radix et Rhizoma are primarily used. Stir-frying with wine can help Paeoniae Radix Alba nourish blood and promote blood circulation, tonifying without stagnation, and it is used in most of the diseases caused by liver qi stagnation or qi and blood deficiency. Glycyrrhizae Radix et Rhizoma used in raw is tonifying without causing stagnation, and it can also have the effect of purging fire. In terms of proportion, the ratio of Paeoniae Radix Alba to Glycyrrhizae Radix et Rhizoma is 5∶1 for liver stagnation restraining spleen, 3∶1 for qi and blood deficiency, and 1∶1 for obvious fire-heat. This paper analyses the application of Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma couplet medicines in FU Qingzhu Nüke, aiming to deeply study and inherit the academic thought of FU Qingzhu, and to provide new ideas and method for the precise application of Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma couplet medicines in clinical practice and researches.

Objective To summarize the best evidence of nutritional support therapy with food for special medi-cal purpose for patients undergoing adjuvant chemotherapy after oncology surgery,and to provide a reference basis for standardizing the application of food for special medical purpose and guiding clinical nutritional therapy practice for oncology patients.Methods Computer search was conducted on UpToDate,Guidelines International Network(GIN),National Guideline Clearinghouse,National Comprehensive Cancer Network,National Institute for Health and Clinical Excellence,Oncology Nursing Society,American Society for Parenteral Enteral Nutrition,European Society for Clinical Nutrition and Metabolism,Chinese Society for Parenteral and Enteral Nutrition,Joanna Briggs Institute Evidence-Based Health Care Centre database,Cochrane Library,PubMed,CINAHL,Scopus,Web of Science,Em-base,CBM,Wanfang,and China Knowledge Network on the nutritional support treatment of food for special medical purpose for postoperative adjuvant chemotherapy patients.The retrieval period was from January 2012 to August 2022.Quality evaluation of the literature was completed independently by 2 evidence-based trained researchers and combined with expert advice to extract and summarise evidence for the literature that met quality standards.Results A total of 14 articles were included,including 4 guidelines,1 clinical decision,2 systematic re views,4 expert consen-suses,and 3 randomized controlled trials.The 14 pieces of best evidence were compiled,covering 6 aspects of nu-tritional screening and assessment,nutritional education,recommended dose,formulation selection,nutritional treat-ment,and management of adverse effects.Conclusion This study summarises the best evidence on the nutritional management of food for special medical purpose in postoperative adjuvant chemotherapy patients with cancer,which is scientific and systematic.When administering nutritional therapy to patients,healthcare professionals should fully assess the nutritional status of patients,make clear and prudent choices on the dosage and type of food for special medical puipose to be used by patients,and guide patients to improve their nutritional status safely and effectively to improve their quality of life.To improve the quality of life.

【Objective】 The thermal effects of super-pulsed thulium fiber laser (TFL) at different powers,lithotripsy modes and irrigation rates were studied using a 3D kidney model to simulate ureteral lithotripsy in vivo. 【Methods】 A thermal effect model was established in vitro. Under the same conditions of laboratory temperature and equipment,the temperature around the optical fiber was measured and compared when different optical fiber diameters,powers,lithotripsy modes and irrigation rates were used to simulate lithotripsy by TFL. 【Results】 There was significant difference in the temperature around the optical fiber caused by two fibers with different diameters under the same conditions (P<0.05). Under the same conditions,different lithotripsic modes produced different temperatures,and the temperature of "high energy and low frequency" was lower than that of "low energy and high frequency" (P<0.05). When the power was 10 W and the minimum irrigation rate was 10 mL/min,the plateau temperature did not reach the safety threshold (43 ℃). When the power was 20 W and the minimum irrigation rate was 10 mL/min,the platform temperature exceeded the safety threshold. When the irrigation rate was 20 mL/min,the platform temperature did not reach the safety threshold. 【Conclusion】 In the study of ureteral lithotripsy in vitro,the power,mode,irrigation rate and optical fiber diameter are factors affecting the thermal effects of TFL. No matter what kind of lithotripsy mode and fiber diameter,the temperature around the fiber is safe when the lithotripsy power is ≤10 W and the irrigation rate is ≥10 mL/min;when the lithotripsy power is ≤20 W and the irrigation rate is ≥20 mL/min,the temperature around the fiber is safe.

Purpose/Significance To explore the characteristics and clinical significance of differentially expressed genes closely re-lated to HPV E6/E7 by using bioinformatics.Method/Process The cervical tissue and clinical information of cervical cancer in TCGA and GTEx of UCSC are used as the training set.The expression profile chip GSE63514 related to cervical cancer in GEO is used as the validation set.Firstly,the limma package of R software is used to screen DEGs of tumor and normal samples,and Venn map of genes re-lated to E6/E7 protein in MigDB is made.Survival analysis is performed by survival kit and verified by ROC and protein expression lev-els.Secondly,key genes are obtained by copy number variation and methylation correlation.Finally,the specific co-expression network is constructed and enrichment analysis and immune infiltration analysis are performed.Result/Conclusion There are 101 differentially expressed genes related to HPV E6/E7 protein,and three genes are found to have significance after screening,namely E2F1,MCM4 and PCNA.At the same time,it is found that the genes in the specific coexpression network are significantly enriched in the DNA replication and chromosome organization pathways.Immune correlation analysis shows that key genes are significantly associated with CD4 T cells,B cells and neutrophils.DNA replication,chromosome organization,etc.,are the molecular mechanisms and key genes significantly related to the development of cervical squamous cell carcinoma and HPV E6/E7 encoded proteins.

Objective:To retrospectively summarize disease characteristics and the clinical experience of minimally invasive endoscopy in the treatment of upper urinary tract obstruction caused by ureteropelvic encrusted inflammatory disease.Methods:Three patients with bilateral ureteropelvic encrusted inflammatory disease admitted to our hospital from March 2018 to July 2021 were involved. Case 1, male, 45 years old, admitted due to bilateral hydronephrosis for 5 months. The preoperative diagnosis were bilateral ureteropelvic stones (encrustation), right ureteral atresia, left ureteral stenosis, and systemic vasculitis. Left double J tube insertion and right nephrostomy were performed in another hospital. We conducted antegrade percutaneous nephroscopy combined with retrograde ureteroscopy surgery and assisted balloon dilation to treat bilateral lesions stage by stage. Case 2, Male, 12 years old, admitted due to bilateral abdominal pain for 6 weeks. The preoperative diagnosis were bilateral ureteral stones, bilateral hydronephrosis, and dermatomyositis. After the failure of double J tube insertion in another hospital, double nephrostomy was performed instead. We performed left percutaneous nephroscopy and right percutaneous nephroscopy combined with ureteroscopy for the treatment of bilateral lesions. Case 3, female, 32 years old, was admitted because of pain in the left lower back and abdomen for over 6 months. The preoperative diagnosis were bilateral ureteral stones, bilateral ureteral stenosis, and dermatomyositis. She underwent three times of ESWL and once URS before. We performed ureteroscopic surgery for bilateral lesions. During the surgery, various degrees of crusting in the renal pelvis or ureter were observed in all 3 cases, and the lesions were removed using pneumatic lithotripsy combined with forceps or baskets. After surgery, oral antibiotics were continuously used for 1-3 months. The efficacy and prognosis were evaluated based on the follow-up of urine, imaging, and endoscopic examinations at 3, 6, and 12 months after surgery.Results:All 3 surgeries were successfully completed. At 3, 6, and 12 months after surgery, follow-up CT showed no crusting in the left ureter, and endoscopy showed good mucosal wound healing and unobstructed lumen in case 1. There were still some crusting lesions and lumen stenosis in the right renal pelvis, and the right ureter reconstruction surgery was ultimately performed. There were no crusting on both sides and the urinary tract was unobstructed after 3, 6, and 12 months of follow-up in case 2 and case 3. Postoperative pathological examination showed chronic inflammation of urothelial mucosal tissue, small pieces of proliferative fibrous tissue with peripheral calcification. Calcification layer composition analysis showed magnesium ammonium phosphate and carbonate apatite. No related complications occurred in case 2 and case 3.Conclusions:Urothelial crusted inflammatory disease is rare clinically, and the diagnosis and treatment strategies are rarely reported domestically and internationally. Preoperative imaging examination, intraoperative findings and postoperative pathology or calcification composition analysis are of instruction for the diagnosis and treatment of this disease. Minimally invasive endoscopy treatment for upper urinary tract obstruction caused by ureteropelvic encrusted inflammatory disease has a good effect. Long-term efficacy and other adjuvant treatment need long-term follow-up and clinical practice.

Engineered probiotics can serve as therapeutics based on their ability of produce recombinant immune-stimulating properties. In this study, we built the recombinant Bacillus subtilis WB800 expressing antimicrobial peptide KR32 (WB800-KR32) using genetic engineering methods and investigated its protective effects of nuclear factor-E2-related factor 2 (Nrf2)‍-Kelch-like ECH-associated protein 1 (Keap1) pathway activation in intestinal oxidative disturbance induced by enterotoxigenic Escherichia coli (ETEC) K88 in weaned piglets. Twenty-eight weaned piglets were randomly distributed into four treatment groups with seven replicates fed with a basal diet. The feed of the control group (CON) was infused with normal sterilized saline; meanwhile, the ETEC, ETEC+WB800, and ETEC+WB800-KR32 groups were orally administered normal sterilized saline, 5×10¹⁰ CFU (CFU: colony forming units) WB800, and 5×10¹⁰ CFU WB800-KR32, respectively, on Days 1‍‒‍14 and all infused with ETEC K88 1×10¹⁰ CFU on Days 15‍‒‍17. The results showed that pretreatment with WB800-KR32 attenuated ETEC-induced intestinal disturbance, improved the mucosal activity of antioxidant enzyme (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)) and decreased the content of malondialdehyde (MDA). More importantly, WB800-KR32 downregulated genes involved in antioxidant defense (GPx and SOD1). Interestingly, WB800-KR32 upregulated the protein expression of Nrf2 and downregulated the protein expression of Keap1 in the ileum. WB800-KR32 markedly changed the richness estimators (Ace and Chao) of gut microbiota and increased the abundance of Eubacterium_rectale_ATCC_33656 in the feces. The results suggested that WB800-KR32 may alleviate ETEC-induced intestinal oxidative injury through the Nrf2-Keap1 pathway, providing a new perspective for WB800-KR32 as potential therapeutics to regulate intestinal oxidative disturbance in ETEC K88 infection.
Animals ; Swine ; Enterotoxigenic Escherichia coli ; Kelch-Like ECH-Associated Protein 1 ; Bacillus subtilis ; NF-E2-Related Factor 2 ; Antioxidants ; Oxidative Stress

Objective:To summarize the preliminary clinical experience of utilizing ureteral balloon dilation catheter in the treatment of "difficult ureter" during ureteroscopic lithotripsy, and to discuss the efficacy and safety of the technique.Methods:Clinical data of 28 patients (30 sides) with upper urinary tract calculi admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University from April 2021 to July 2022 were retrospectively analyzed. There were 23 males (82.1%) and 5 females (17.9%), with age of (51.5±13.6) years. Among the 30 sides, 20 (66.7%) on the left and 10(33.3%) were on the right. Calculi were either located in the renal pelvis or calyxes in 7 sides (23.3%), upper ureter in 17 sides (56.7%), and lower ureter in 6 sides (20.0%). The maximum diameter of the stones was (9.4±4.2)mm, and 23 sides (76.7%) were combined with hydronephrosis before surgery. When "difficult ureter" was encountered during the procedure, that is, it was difficult to insert ureteroscope or ureteral access sheath (UAS) due to small ureteral lumen, balloon catheter was used for dilation in the first stage, in which the balloon diameter was 4 mm on 22 sides and 5mm on 8 sides. The instrument was retrogradely inserted through the working channel of F8 semi-rigid ureteroscope, and the small site of the ureteral lumen was dilated under direct endoscopic view. After a single dilation, the balloon catheter was withdrawn, and the effect of dilation was evaluated by semi-rigid ureteroscopy to determine whether to proceed with the following procedures. The intraoperative data were recorded, including surgical method, stage of "difficult ureter" occurred, site of the small part of the ureter, related data of utilizing ureteral dilatation balloon catheter, grade of ureteral injury after dilatation (according to the 0-4 grading classification of endoscopic ureteral injuries), total operation time, balloon catheter-related adverse events, stone-free rate, and time of removing ureteral stents.Results:Among the 30 sides, 29 (96.7%) had difficulty in the stage of ureteroscope insertion, and 1(3.3%) had difficulty in the stage of UAS insertion. A total of 37 small sites of ureter were involved, including 18 in the intramural segment, 10 in the lower part, 2 in the middle part, and 7 in the upper part. Each site was dilated once with a median time of 3 (0.5, 5.0) minutes and a median maximum balloon pressure of 1 215.9(1 215.9, 1 443.9)kPa[12.0(12.0, 14.3)atm]. There were 28 sites of grade Ⅰ injury, 8 sites of grade Ⅱinjury, and 1 site of grade Ⅲinjury. The total duration of unilateral procedure was (73.4±30.3) min. Ureteroscope or UAS insertion was successful in 28 sides(93.3%) after balloon dilation, and failed in 2 sides(6.7%), both of which were in the stage of inserting ureteroscope and ureteral stent was indwelled for the second-stage procedures. On the first day after surgery, the hemoglobin level was (134.1±12.9)g/L, which was significantly different from the preoperative parameters ( P<0.01), and serum creatinine level was (86.7±23.2)μmol/L, which showed no significant difference from the preoperative one ( P=0.263). The primary stone-free rate was 92.9% (26/28), and the total postoperative complication rate was 13.3% (4/30), including 3 of grade Ⅰ (lateral lower abdominal pain requiring additional analgesic drugs) and 1 of grade Ⅱ (postoperative hematuria requiring intravenous hemostatic drugs). Follow-up was conducted for 3 months. All of the 28 successful sides had their ureteral stents removed before the last follow-up, and the time of removal was (36.9±11.5) days. No hydronephrosis was found in the ipsilateral kidney by ultrasound 3 months after operation. Conclusions:Balloon dilation technique showed good efficacy and safety in the treatment of "difficult ureter" during ureteroscopic lithotripsy.

Objective:To compare the temperature rise curve and steady-state temperature of thulium and holmium laser in lithotripsy.Methods:This study was conducted from November to December 2021. Firstly, we designed an experimental water tank(10 cm×10 cm×10 cm) that can carry out constant temperature water bath, with a 8ml simulated renal pelvis, and can carry out constant velocity perfusion in the simulated renal pelvis. A 1 cm×1 cm×1 cm cubic artificial stone was placed in the simulated renal pelvis to perform 36.5℃-37.5 ℃ water bath. The simulated renal pelvis was closed with an oak plug, the temperature measuring probe and flexible ureteroscope were placed through the hole on the oak plug and entered into the simulated renal pelvis. Flexible ureteroscope was carried out by urologists. The lithotripsy lasted a total of 180 seconds for thulium and holmium laser respectively under different parameter settings (10 Hz×1.0 J, 10 Hz×2.0 J, 10 Hz×3.0 J, 20 Hz×0.5 J, 20 Hz×1.0 J, 20 Hz×1.5 J, the corresponding gravel power is 10 W, 20 W and 30 W respectively), the constant speed water pump flow rate was separate as the high flow rate group (35 ml/min) and low flow rate group (15ml/min), and leave a temperature probe 5mm around the optical fiber. Water temperature change during the lithotripsy was recorded by probes, the average of 10 temperature values of two probes measured every 5 seconds was taken as the water temperature value of this period, with a total of 216 time points in 6 parameter settings. Under the same parameter settings, the temperature of two lasers at each time point was plotted and compared to form the corresponding temperature rise curve. The average temperature in the last 30 seconds during lithotripsy in the record was used as the steady-state temperature, which of thulium and holmium laser lithotripsy was compared under the same parameter setting and the same water flow velocity. Finally, 43℃ was taken as the safety threshold temperature to evaluate whether the temperature of the two lasers during lithotripsy exceeds the safety threshold.Results:According to the temperature rise curve, the water temperature of thulium laser during lithotripsy was higher than that of holmium laser at 77.7% (168/216)of time points. At the flow rate of 15 ml/min, thulium laser was significantly higher than that of holmium laser at 10 Hz×1.0 J[(32.43±2.19℃)vs. (30.99±0.90)℃, P<0.01], 10 Hz×2.0 J[(41.21±3.30℃) vs. (38.13±1.26)℃, P<0.01], 10 Hz×3.0 J[(49.54±2.44)℃vs. (44.91±0.65)℃, P<0.01], 20 Hz×0.5 J[(32.75±1.41)℃vs. (30.84±1.16)℃, P<0.01], 20 Hz×1.0 J[(41.67±1.76)℃vs. (37.51±1.25)℃, P<0.01], 20 Hz×1.5 J [(47.54 ± 3.48)℃vs. (46.12±1.04)℃, P<0.01]. At the flow rate of 35 ml/min, the thulium laser was significantly higher than that of holmium laser at 10 Hz×1.0 J[(28.01±0.57)℃ vs. (26.84±0.97)℃, P<0.01], 10 Hz×2.0 J[(31.31±1.07)℃vs.(30.41±1.39)℃, P<0.01], 10 Hz×3.0 J[(33.29±0.70)℃vs.(32.25±2.55)℃, P<0.01], 20 Hz×0.5 J[(28.36±0.99)℃vs.(26.22±0.66)℃, P<0.01], 20 Hz×1.0 J [(30.80±2.06)℃vs.(30.08±0.78)℃, P=0.012], and the steady-state temperature was not significant different between two laser at 20 Hz×1.5 J [(34.54±3.08)℃ and(33.93±1.49)℃, P=0.163]. In the low flow rate group, thulium laser at 10 Hz×1.0 J, 10 Hz×2.0 J, 20 Hz×0.5 J and 20 Hz×1.0 J does not exceed the safety threshold temperature, while in the high flow rate group, any combination of laser parameters of the two lasers does not exceed the safety threshold temperature. Conclusion:Under the same laser parameter setting and flow rate, the thermal eff of thulium laser is more obvious. When using thulium laser for lithotripsy, the flow rate in the process of lithotripsy being faster than that of holmium laser with the same laser setting should be ensured to avoid tissue damage.

Volatile oil microemulsion gel of traditional Chinese medicine has the dual characteristics of microemulsion and gel， which can improve the solubility and stability of drugs， promote drug absorption and achieve long-term sustained release effect. In recent years， it has been widely used in clinical diseases such as internal medicine， gynecology and pediatrics. In this paper， the characteristics， prescription design， molding process and quality evaluation of volatile oil microemulsion gel of traditional Chinese medicine were reviewed by searching relevant literature. The results showed that the volatile oil microemulsion gel had the characteristics of improving the stability of the drug， increasing the transdermal penetration of the drug， strong adhesion， easy to wash， convenient preparation， etc. The prescription design consists of oil phase， surfactant， cosurfactant and gel matrix. The molding process includes the molding process of microemulsion and the molding process of gel， and the formation of microemulsion mainly uses the pseudo-ternary phase diagram method. The quality evaluation can be divided into 2 parts： volatile oil of traditional Chinese medicine and microemulsion gel. The quality evaluation of volatile oil can be studied qualitatively and quantitatively. Microemulsion gel should meet the relevant requirements and be tested for in vitro release and transdermal absorption.