OBJECTIVE To prepare polyethylene glycol （PEG）-modified flower lactose （FL） loaded Curcumin （Cur） solid lipid nanoparticle （SLN） inhalable micropowder （referred to as “PEG-Cur-FL”）. METHODS PEG-Cur-FL was prepared by the solvent emulsification diffusion low-temperature solidification method， and its encapsulation efficiency， drug loading capacity， powder properties， aerodynamic particle size， in vitro deposition properties， and in vitro release characteristics were characterized. The mice were divided into Cur-SLN-FL （unmodified with PEG） group and PEG-Cur-FL group， with 55 mice in each group. Both groups of mice were given a single inhalation of 5 mg/kg （calculated as Cur） of the corresponding drug micropowder through an air tube. At 0.25， 0.5， 1， 2， 4， 6， 8， 12， 24， 48 and 72 hours after administration， eyeballs were removed to collect blood and tracheal， lung， liver and kidney tissues were separated. The mass concentration of Cur in mouse plasma and various tissue samples was measured， and the tissue distribution and retention of the drug were analyzed. RESULTS The encapsulation efficiency and drug loading capacity of PEG-Cur-FL were （86.2±1.8）% and （4.2±0.2）%， respectively； the bulk density and tap density were （0.24±0.01） g/cm3 and （0.30±0.01） g/cm3， respectively； the aerodynamic particle size was （2.74±0.64） μm； the in vitro effective site deposition rate （secondary drug deposition rate） was （45.07±2.79）%. Compared with Cur raw materials， Cur-SLN- FL and PEG-Cur-FL had sustained release effects under both leakage and non-leakage conditions， and PEG-Cur-FL had a smoother sustained release in artificial lung fluid， with release characteristics consistent with the Weibull model. The results of in vivo distribution showed that the drug concentration in the lung tissue of PEG-Cur-FL group was significantly lower than that of Cur- SLN-FL group during the same period after 1 hour of administration， while the drug concentration in the lung tissue at 4 to 48 hours was significantly higher than that of Cur-SLN-FL group during the same period （P＜0.05）； the plasma drug concentrations of the PEG-Cur-FL group at all time points from 0.25 to 12 hours were significantly lower than those of the Cur-SLN-FL group during the same period （P＜0.05）， and the drug concentrations in liver and kidney tissues were also lower than those of the Cur-SLN-FL group during the same period （P＜0.05）. CONCLUSIONS PEG-Cur-FL is prepared successfully； the inhalable micropowder has good inhalability and release performance； after administration through the trachea， the effective concentration of Cur in lung tissue can be increased， while reducing its plasma drug concentration and drug distribution concentration in non-target organs.

The rare-earth-elements-doped upconversion nanoparticles NaYF4:Yb3+,Er3+were synthesized by solvothermal method,and NaYF4:Yb3+,Er3+@SiO2 were prepared by coating SiO2 on the surface of NaYF4:Yb3+,Er3+by inverse microemulsion method in this work.Based on the fluorescence quenching principle between NaYF4∶Yb3+,Er3+@SiO2 and SQA-Fe3+,a NaYF4∶Yb3+,Er3+@SiO2-SQA-Fe3+fluorescence nanosensor was constructed for detection of trace hydrogen peroxide(H2O2).Under optimal conditions,the linear range of this method for detecting H2O2 was 1.8?84.0 μmol/L,with detection limit(3σ)of 0.47 μmol/L.The recoveries of H2O2 spiked in milk were 98.4%?99.7%.This method could be used for detection of H2O2 residue in milk samples,with advantages such as low detection limit,good stability and strong anti-interference ability.

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.
Humans ; Male ; Female ; Adult ; Aged, 80 and over ; Antiviral Agents/therapeutic use* ; Hepatitis B, Chronic/epidemiology* ; Hepatitis B e Antigens ; Hepatitis B/drug therapy* ; Hepatitis B Surface Antigens ; Hepatitis A ; Liver Cirrhosis/drug therapy* ; China/epidemiology* ; Registries ; Hepatitis B virus/genetics* ; DNA, Viral

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
Mice ; Male ; Animals ; Lactic Acid/pharmacology* ; Intestinal Mucosa ; Colon/pathology* ; Dexamethasone/pharmacology* ; Diet, High-Protein ; Pneumonia/pathology*

Objective: To investigate the application effect of augmented reality and mixed reality navigation technology in three-dimensional(3D) laparoscopic narrow right hepatectomy(LRH). Methods: A retrospective analysis was performed on the clinical data of 5 patients with hepatic malignancy admitted to the First Department of Hepatobiliary Surgery,Zhujiang Hospital,Southern Medical University from September 2020 to June 2021,all of whom were males,aged from 42 to 74 years.Preoperative evaluation was performed using the self-developed 3D abdominal medical image visualization system; if all the 5 patients were to receive right hemihepatectomy,the remnant liver volume would be insufficient,so LRH were planned.During the operation,the independently developed 3D laparoscopic augmented reality and mixed reality surgical navigation system was used to perform real-time multi-modal image fusion and interaction between the preoperative 3D model and 3D laparoscopic scene.Meanwhile,intraoperative ultrasound assisted indocyanine green fluorescence was used to determine the surgical path.In this way,the LRH under the guidance of augmented reality and mixed reality navigation was completed.The predicted liver resection volume was evaluated before surgery,actual resected liver volume,surgical indicators and postoperative complications were analyzed. Results: All the 5 patients completed LRH under the guidance of augmented reality and mixed reality navigation technology,with no conversion to laparotomy.The median operative time was 300 minutes(range:270 to 360 minutes),no intraoperative blood transfusion was performed,and the median postoperative hospital stay was 8 days(range:7 to 9 days).There were no perioperative deaths,or postoperative complications such as liver failure,bleeding,or biliary fistula. Conclusion: For patients who need to undergo LRH,the use of augmented and mixed reality navigation technology can safely and effectively guide the implementation of surgery,retain more functional liver volume,improve surgical safety,and reduce postoperative complications.
Adult ; Aged ; Augmented Reality ; Hepatectomy/methods* ; Humans ; Imaging, Three-Dimensional ; Laparoscopy/methods* ; Liver Neoplasms/surgery* ; Male ; Middle Aged ; Retrospective Studies ; Technology

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

Objective:To compare the effects of phenoxybenzamine and doxazosin on intraoperative hemodynamics in patients with normotensive pheochromocytoma.Methods:Perioperative data of patients who underwent surgery for normotensive pheochromocytoma in Peking University First Hospital from January 1, 2004 to December 31, 2017 were collected.Patients were divided into phenoxybenzamine group and doxazosin group according to the type of preoperative α-blockade.The primary endpoint was intraoperative hemodynamic fluctuations.Secondary endpoints included postoperative circulatory support, complications, mortality, and etc.Results:Sixty-one patients were included in the study, with 24 cases in phenoxybenzamine group and 37 cases in doxazosin group.There was no significant difference in the area under the curve of intraoperative blood pressure fluctuation between the two groups ( P>0.05). The area under the curve of intraoperative heart rate >110 bpm was significantly greater in phenoxybenzamine group than in doxazosin group ( P<0.05). There was no significant difference in the secondary endpoints between the two groups ( P>0.05). Conclusion:The effect of preoperative administration of doxazosin or phenoxybenzamine on blood pressure fluctuation has no significantly statistical difference in patients with normotensive pheochromocytoma, and the patients took phenoxybenzamine preoperatively have an increased risk of intraoperative tachycardia.

Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.

Objective To evaluate the risk factors for intraoperative hemodynamic instability (HI) in patients with adrenal incident pheochromocytoma.Methods Perioperative clinical parameters of patients undergoing surgery for adrenal incident pheochromocytoma at the First Hospital of Peking University from January 2001 to July 2018 were analyzed.There were 39 males and 41 females,with mean age of 45.1 years (13-76 years old).The median tumor length was 5.1 cm (1.5-14.0 cm),with 25 cases (31.3％) on the left side,55 cases (68.8％) on the right side.There were 37 cases combined with coronary heart disease or diabetes or BMI≥24 kg/m2.Patients were divided into hemodynamic instability (HI group) and hemodynamic stability group (HS group) by whether intraoperative hemodynamic instability occurred.The differences of demographic characteristics and clinical parameters between the two groups were compared.Logistic regression analysis was done for seeking the risk factors for hemodynamic instability during surgery.Results There were 54 cases (67.5％) in the HS group and 26 cases (32.5％) in the HI group.Univariate analysis showed that there was no significant difference in age [(44.06 ± 13.58) years old vs.(47.35 ± 16.11) years old],combined with coronary heart disease or diabetes or BMI≥24 kg/m2 [50.0％(27/54) vs.38.5％ (10/26)],tumor long diameter [median 5.0 cm(1.5-14.0 cm) vs.6.0cm(1.5-13.5 cm)],tumor location [left:29.6％ (16/54) vs.34.6％ (9/26)],preoperative catecholamine test positive [44.4％ (20/45) vs.50.0％ (10/20)],open surgery [27.8％ (15/54) vs.34.6％ (9/26)]and preoperative non-alpha blockers[13.0％ (7/54) vs.30.8％ (8/26)] between HS group and HI group (P ＞ 0.05).Further logistic regression analysis was used to analyze the risk factors of intraoperative hemodynamic instability.Multivariate analysis found that patients who preoperative non-alpha blockers before surgery were independent risk factor for HI (OR =4.574,95 ％ CI 1.273-16.432,P =0.020).Conclusions Preoperative non-alpha blocker in patients with adrenal incidental pheochromocytoma could be independent risk factor for intraoperative hemodynamic instability.Therefore,it is recommended that patients with adrenal incidental tumors,especially those who fail to rule out pheochromocytoma,take preoperative alpha blockers.