Objective:To investigate the effect and mechanism of Grifola frondosa extract on inflammatory response of colon tissue in rats with ulcerative colitis(UC)by regulating interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods:Forty SD rats were randomly divided into blank control group,UC model group,Grifola frondosa treatment group,western medicine treatment group and combined treatment group,with 8 rats in each group.After UC rats were established by free drinking 3%DSS for 7 days,the treatment group were given Grifola frondosa extract 10 mg/(kg·d),sulfasalazine 0.3 g/(kg·d),and the same amount of two drugs,for 14 consecutive days.During the experiment,general state of rats were observed,and the disease activity index(DAI)score was calculated;pathological changes of rats colon tissue were observed by HE staining;protein expression levels of IL-6,JAK2,STAT3 and p-STAT3 in rats colon tissue were detected by Western blot;content of IL-6 in rats serum was detected by ELISA;protein contents and expressions of IL-6R and MPO in rats colon tissue were determined by immunohistochemistry.Results:Compared with blank control group,general state of rats in UC model group was poor,DAI score was increased,obvious tissue mucosal defects and inflammatory cell infiltration were observed by HE staining;protein expression levels of IL-6,JAK2,STAT3 and p-STAT3 in rats colon tissue and contents of IL-6R and MPO were significantly increased(P<0.01);content of IL-6 in rats serum was significantly increased(P<0.01),the difference was statistically significant.Compared with UC model group,general condition of rats in each treatment group was improved,DAI score was decreased,HE staining showed that mucosal defects were improved to varying degrees,and occasionally inflammatory cell infiltration was observed;protein expression levels of IL-6,JAK2,STAT3 and p-STAT3 in colon tissue were significantly decreased(P<0.01),contents of IL-6R and MPO in colon tissue and content of IL-6 in serum were significantly decreased(P<0.01 or P<0.05),the differences were statistically significant.Conclusion:Grifola frondosa extract can reduce the inflammatory response in colon tissue of UC rats by regulating expressions of IL-6/JAK2/STAT3 signaling pathway related factors.

Objective:To investigate the etiological distribution of hydronephrosis caused by upper uri-nary tract obstruction in adult patients and to improve the diagnostic accuracy for this condition.Me-thods:The clinical information of adult patients with newly diagnosed hydronephrosis in Upper Urinary Tract Repair Outpatient Clinic of Peking University First Hospital from May 2020 to May 2021 were pro-spectively and continuously collected.Patients with ureteral calculi or upper urinary tract tumor were ex-cluded.A total of 767 patients were involved.The underlying causes of upper urinary tract obstruction were identified by senior urological surgeons according to symptoms,medical history,physical examina-tion,and a range of diagnostic imaging techniques including ultrasound,computed tomography(CT),magnetic resonance imaging(MRI),retrograde pyelography,antegrade pyelography,radionuclide reno-gram and ureteroscopy.Results:Among the 767 patients,359(46.8％)were male and 408(53.2％)were female.The median age of these patients was 37 years(range,14-84 years).Hydronephrosis was observed at left-sided in 357 cases(46.6％),right-sided in 251 cases(32.7％),and bilateral in 159 cases(20.7％).The causes of hydronephrosis were classified as follows:(1)Non-iatrogenic factors were found in 464 cases(60.5％).These included urinary malformations in 355 cases(76.5％),infec-tion in 29 cases(6.3％),pelvic lipomatosis and/or cystitis glandularis in 23 cases(5.0％),ureteral en-dometriosis in 18 cases(3.9％),retroperitoneal fibrosis in 15 cases(3.2％),trauma in 7 cases(1.5％)and other non-iatrogenic factors in 12 cases(2.6％).Some of these patients had multiple non-iatrogenic causes.Among the 355 cases with urinary system malformations,252 cases(71.0％)had ureteropelvic junction obstruction.(2)Iatrogenic ureteral injuries accounted for 210 cases(27.4％),including 112 cases(53.3％)of urological surgical injuries,51 cases(24.3％)of radiotherapy for malignant tumor re-lated injuries,34 cases(16.2％)of gynecological and obstetrical surgical injuries,and 13 cases(6.2％)of general surgical injuries.(3)The cause of hydronephrosis remained unknown in 93 cases(12.1％).Conclusion:Hydronephrosis in adults due to upper urinary tract obstruction has a diverse range of cau-ses,with urinary malformations and iatrogenic ureteral injuries being significant contributors.Urological surgeon involved in upper urinary tract reconstruction should be familiar with these potential causes to fa-cilitate accurate diagnosis and effective treatment.

The blood-brain barrier (BBB) plays a crucial role in maintaining the homeostasis of the brain's internal environment, which poses challenges to the treatment of central nervous system diseases. Drug carriers can aid in the delivery of therapeutic agents across the BBB to exert their pharmacological effects. The article reviewed the pathways for drug delivery across the BBB, the intracerebral fate and the classification of drug carriers and focuses on the functions and characteristics of liposomes, exosomes, apoptotic bodies, cell-penetrating peptides, and cell-targeting peptides. The review will provide an outlook on the future and challenge of research in the field of drug delivery across the BBB.

Metastasis is the main risk factor for poor prognosis of laryngeal squamous cell carcinoma (LSCC) .Chemokines are closely related to metastasis in the tumor microenvironment.CXCL8 is a cyto-kine-like secreted protein that plays key roles in the malignant development of a variety of tumors,but has not been elucidated in LSCC.In this paper,we elucidated the role of CXCL8 in LSCC cells and found miRNAs that targeted CXCL8,which may become new targets for the diagnosis and treatment of LSCC.Firstly,the GEPIA showed that CXCL8 was highly expressed in head and neck cancer (P<0.05).The real-time fluorescence quantification (qRT-PCR) found that CXCL8 was highly expressed in LSCC cells.The enzyme-linked immunoassay also found that CXCL8 was highly secreted in the superna-tant of LSCC cells (P<0.001) .Then,the CCK8 assay confirmed that knockdown of CXCL8 significant-ly inhibited the proliferation of FD-LSC-1 and AMC-HN8 cells (the average inhibition rate was 34.0％and 19.5％,respectively);The EdU assay also confirmed that knockdown of CXCL8 significantly inhibi-ted the proliferation of LSCC cells (P<0.05) .The transwell assay confirmed that knockdown of CXCL8 also significantly inhibited the migration and invasion of FD-LSC-1 cell (average inhibition rate was 40.0％,38.5％,respectively);Knockdown of CXCL8 also significantly inhibited the migration and inva-sion of AMC-HN8 cell (average inhibition rate was 37.5％,53.5％,respectively ) .The analysis of bioinformatics predicted that CXCL8 may be a target of miR-513b-5p.The dual luciferase reporter assay confirmed that miR-513b-5p could bind to the CXCL8-3'UTR.QRT-PCR assay also confirmed that over-expression of miR-513b-5p could decrease the 60％ of the CXCL8 expression (P<0.01) .Cell function rescue assays found that overexpressed of CXCL8 could effectively reversed proliferation,migration and invasion of LSCC cells weakened by miR-513b-5p (P<0.05) .In summary,miR-513b-5p inhibited the proliferation,migration and invasion of LSCC cells by targeting CXCL8.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ² test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ²=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ²=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.
Male ; Female ; Humans ; Retrospective Studies ; Pancreatitis, Acute Necrotizing/complications* ; Acute Disease ; Intraabdominal Infections/complications* ; Necrosis/complications* ; Treatment Outcome

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

Harmaline and harmine are β-carboline alkaloids with effective pharmacological effects. Harmaline can be transformed into harmine after oral administration. However, enzymes involved in the metabolic pathway remain unclear. In this study, harmaline was incubated with rat liver microsomes (RLM), rat brain microsomes (RBM), blood, plasma, broken blood cells, and heme peroxidases including horseradish peroxidase (HRP), lactoperoxidase (LPO), and myeloperoxidase (MPO). The production of harmine was determined by a validated UPLC-ESI-MS/MS method. Results showed that heme peroxidases catalyzed the oxidative dehydrogenation of harmaline. All the reactions were in accordance with the Hill equation. The reaction was inhibited by ascorbic acid and excess H₂O₂. The transformation of harmaline to harmine was confirmed after incubation with blood, plasma, and broken blood cells, rather than RLM and RBM. Harmaline was incubated with blood, plasma, and broken cells liquid for 3 h, and the formation of harmine became stable. Results indicated an integrated metabolic pathway of harmaline, which will lay foundation for the oxidation reaction of dihydro-β-carboline. Moreover, the metabolic stability of harmaline in blood should not be ignored when the pharmacokinetics study of harmaline is carried out.
Animals ; Harmaline/metabolism* ; Harmine/metabolism* ; Heme ; Hydrogen Peroxide ; Rats ; Tandem Mass Spectrometry

Objective:To evaluate the efficacy and side effects of PD-1 monoclonal antibody in the treatment of advanced metastatic renal cell carcinoma in China.Methods:The clinical data of 117 patients with advanced metastatic renal cell carcinoma (mRCC) treated with PD-1 monoclonal antibody from October 2016 to February 2022 were retrospectively analyzed. There were 87 males (74.4%) and 30 females (25.6%), with an average age of (57.9±10.9) years old, BMI of (23.6±3.4) kg/m 2and smoking history of 79 (67.5%). There were 44 cases (37.6%) with hypertension, 19 (16.2%) cases of diabetes. The ECOG score of 59.8% (70/117) patients was 0, 33.3% (39/117) was 1, 4.3% (5/117) was 2, and 2.5% (3/117) was 3. The pathological type of 104 cases were renal clear cell carcinoma (ccRCC), 8 cases of papillary renal cell carcinoma, 2 cases of chromophobe cell carcinoma, 2 cases of collecting duct carcinoma and 1 case of eosinophilic cell carcinoma. The general condition of the overall population and the overall survival (OS) of relevant subgroups were analyzed. Secondary goals included progression free survival (PFS), objective response rate (ORR), adverse reactions, overall survival (OS), and progression free survival (PFS). Results:65.8% (77 / 117) of the patients chose targeted combined with PD-1 monoclonal antibody in the first-line treatment. The main targeted drugs were acitinib (81.8%, 63 / 77), tirelizumab (37.6%, 29 / 77) and cindilimab (25.9%, 20 / 77). After first-line treatment, 19.6.1% (23 / 117) patients needed to be converted to second-line treatment, and 15 patients changed the type of PD-1 antibody during treatment. In addition, the targeted drug of combined therapy was replaced by acitinib in 8 patients. The main causes of drug withdrawal were disease progression (70.7%, 29 / 41) and death (29.2%, 12 / 41). The median OS of the overall population was 35.6 (19-60) months and PFS was 12.1 (1-60) months. The ORR of the overall population was 47.8% (56 / 117). 4.2% (5/117) patients had complete remission, another 17.0% (20/117) patients were in stable condition, and 43.5% (51 / 117) patients were in partial remission. In the first-line treatment, the median PFS time of targeted combined with PD-1 monoclonal antibody was 12.6 (1-30) months, the median PFS time of PD-1 single drug immunotherapy was 10.5 (1-60) months. In the second-line treatment, the PFS of patients treated with PD-1 monoclonal antibody was 10.1 (4-19) months, and that of patients treated with PD-1 monoclonal antibody combined with targeted therapy was 11.7 (1-25) months. The most common adverse reactions were elevated blood pressure (18.5%, 23 / 124), followed by hypothyroidism (15.3%%, 19/124), rash (14.5%, 18 / 124), elevated transaminase (10.5%, 13 / 124) and bone marrow suppression (9.7%, 12/124). 9.4% (11 / 117) patients needed to reduce the related adverse reactions by interrupting the treatment control of PD-1 monoclonal antibody.Conclusions:The safety and efficacy of PD-1 monoclonal antibody in domestic patients are better, and the side effects are less. The efficacy and safety of PD-1 monoclonal antibody combined with targeted therapy in the real world population are consistent with many key clinical trials abroad. PD-1 monoclonal antibody combined with targeted drugs can be popularized in the domestic MRCC population.

OBJECTIVE: To investigate the correlation between drinking habits and pathological characteristics of patients with upper tract urothelial carcinoma (UTUC). METHODS: A preoperative questionnaire survey was conducted to understand the drinking habits of UTUC patients who were admitted to the Department of Urology, Peking University First Hospital for radical nephroureterectomy within one year from August 2020 to July 2021, and statistical analysis was performed in combination with their postoperative pathological characteristics. The statistical procedure was performed using SPSS 22.0 software, and firstly, the preliminary analysis was performed one by one using the columnar χ² test on the pathological characteristics of UTUC tumors as the dependent variable and the factors related to patients' general information, past history and drinking habits as the independent variables, and the independent variables that met P < 0.2 between the case and control groups for each dependent variable were specified for screening. The screened variables were included in the binary Logistic regression analysis. A difference of P < 0.05 was used to indicate a statistically significant difference. RESULTS: A total of 239 patients, 134 males and 105 females, with a mean age of (68.1±9.98)years and a median disease duration of 4.8 months, were included in this study. Multifactorial Logistic regression results suggested that after adjusting for the effects of other variables, UTUC patients who had the habit of drinking at least once every hour during the daytime had a significantly increased risk of high grade (G3) tumors(OR=1.941, 95%CI: 0.352-1.029, P < 0.01); these patients also had a significantly decreased risk of multifocal UTUC tumors (OR=0.344, 95% CI: 1.18-5.582, P=0.004). The patients who had the habit of drinking over 100 mL water each time had a significantly decreased risk of mutifocal UTUC incidence (OR=0.477, 95%CI: 0.225-1.012, P=0.046). Patients who pay attention to daily water intakes had a significantly increased risk of renipelvic carcinoma (OR=2.530, 95%CI: 1.434-4.463, P=0.001) and a significantly decreased risk of ureteral carcinoma (OR=0.314, 95%CI: 0.172-0.573, P < 0.01). Other variables included in the regression model did not differ significantly in their effects on the occurrence of tumor pathological characteristics. CONCLUSION Having the awareness of drinking water every 1 h during the day, drinking over 100 mL water each time, having the awareness of daily drinking habits correlated significantly with pathological characteristics of UTUC such as the presence of G3 tumor, multifocal tumors and location of the tumor. This conclusion still needs to be verified by subsequent trials with higher levels of evidence.
Carcinoma, Transitional Cell/surgery* ; Female ; Habits ; Humans ; Male ; Neoplasm Recurrence, Local/epidemiology* ; Retrospective Studies ; Ureteral Neoplasms/surgery* ; Urinary Bladder Neoplasms/surgery* ; Water