Aim To study the effect of emetine on in-sulin secretion through glucagon-like peptide-1 receptor(GLP-1R).Methods Isolating rat islets were used to carry out insulin secretion experiment.Islets were incubated with different concentrations of emetine(2,10,50 μmol·L-1),different concentrations of glu-cose solution(2.8,11.1,16.7 mmol·L-1)or spe-cific GLP-1R antagonist Exendin(9-39).The amount of insulin secretion in the supernatant of each group was determined by an enzyme-linked radioimmunoas-say.Small molecule compounds were docked to GLP-1R(PDB code:5NX2)using SYBYL-X2.0 software.Results Emetine could promote insulin secretion in high glucose(11.1 mmol·L-1)in a dose-dependent manner.In low glucose(2.8 mmol·L-1),insulin secretion did not change after intervention of emetine.But in high glucose(11.1,16.7 mmol·L-1),insu-lin secretion significantly increased under the treatment of emetine in a glucose-dependent manner.The doc-king score of emetine and GLP-1R was Total Score=6.82,C Score=5,indicating that emetine had a good binding affinity with GLP-1R.Using Exendin(9-39)to block GLP-1R,the insulinotropic effect of emetine was reduced.Conclusion Emetine could promote in-sulin secretion,which is related to the activation of GLP-1R.

Objective To explore the effects of preoperative anxiety on intraoperative body temperature,adverse reactions during recovery and incision healing in elderly patients undergoing radical mastectomy under general anesthesia.Methods A total of 139 elderly patients who underwent radical mastectomy under general anesthesia in the Fourth Affiliated Hospital of Nanjing Medical University from January 2020 to December 2022 were selected as the study objects,and they were divided into the non-anxiety group(87 cases)and the anxiety group(52 cases)according to whether they were complicated with anxiety before surgery.The nasopharyngeal temperature before surgery,after 30 minutes,60 minutes,90 minutes of surgery and at the end of surgery,the ratio of intraoperative nasopharyngeal temperature<36.0℃,the ratio of perioperative blood loss>300 mL,the occurrence of adverse reactions during the recovery period and the incision healing of patients in the two groups were compared.Results There was no statistically significant difference in the nasopharyngeal temperature before surgery and after 30 minutes of surgery of patients between the two groups(P>0.05).After 60 minutes,90 minutes of surgery and the end of surgery,the nasopharyngeal temperatures of patients in the anxiety group were lower than those in the non-anxietey group,and the differences were statistically significant(P<0.05).There were statistically significant differences in the nasopharyngeal temperature at different times of patients in the two groups(P<0.05).The ratios of patients with intraoperative nasopharyngeal temperature<36.0℃and perioperative blood loss>300 mL in the anxiety group were higher than those in the non-anxiety group,and the differences were statistically significant(P<0.05).The incidence of delayed awakening,shivering reaction,and poor postoperative incision healing in the anxiety group were higher than those in the non-anxiety group,with statistically significant differences(P<0.05).Conclusion Elderly patients undergoing radical mastectomy under general anesthesia combined with anxiety show obvious temperature drop after 60 minutes of surgery,and perioperative blood loss has significantly increased,with a higher incidence of intraoperative hypothermia,adverse reactions during recovery and poor postoperative incision healing,which should arouse clinical attention.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the clinical efficacy of Bushen Yijing Decoction for the treatment of xerophthalmia of kidney yang deficiency type and to observe its effect on serum Th1/Th17 cytokines.Methods From January 2021 to January 2023,a total of 96 patients with xerophthalmia of kidney yang deficiency type were selected as the study objects.According to the treatment methods,the patients were divided into observation group and control group,with 48 cases in each group.The control group was treated with Sodium Hyaluronate Eye Drops externally,and the observation group was given oral use of Bushen Yijing Decoction together with Sodium Hyaluronate Eye Drops externally.The course of treatment for the two groups covered 21 days.The changes of tear film break-up time(BUT),corneal fluorescein staining(FL)score,SchirmerⅠtest(SIT)value,serum Th1/Th17 cytokines,Ocular Surface Disease Index(OSDI)questionnaire scores,and 25-Item National Eye Institute Visual Function Questionnaire(NEI-VFQ-25)score in the two groups were observed before and after treatment.Moreover,the clinical efficacy and incidence of adverse reactions were compared between the two groups.Results(1)After 21 days of treatment,the total effective rate of the observation group was 95.83%(46/48),and that of the control group was 70.83%(34/48).The intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the ocular surface function indicators of BUT and SIT values in the two groups were higher and the FL values were lower than those before treatment(P＜0.05).The increase of BUT and SIT values and the decrease of FL values in the observation group were significantly superior to those in the control group(P＜0.01).(3)After treatment,the levels of serum cytokines of interleukin 17(IL-17),tumor necrosis factor alpha(TNF-α)and interferon gamma(IFN-γ)in the two groups were lower than those before treatment(P＜0.05),and the decrease of serum IL-17,TNF-α and IFN-γ levels in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the questionnaire scores of OSDI in the two groups were lower and the NEI-VFQ-25 scores were higher than those before treatment(P＜0.05).The decrease of OSDI scores and the increase of NEI-VFQ-25 scores in the observation group were significantly superior to those in the control group(P＜0.01).(5)The incidence of adverse reactions in the observation group was 4.17%(2/48),and that in the control group was 8.33%(4/48).There was no significant difference between the two groups(P＞0.05).Conclusion Bushen Yijing Decoction can enhance the clinical efficacy of xerophthalmia of kidney yang deficiency type,and the decoction is effective on alleviating the eye discomforts,improving the ocular surface function of patients,regulating the levels of Th1/Th17 cytokines,and relieving the inflammatory response without inducing severe adverse reactions while with high safety.

Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Objective: To forecast mortality, age-standardized mortality, and probability of premature mortality from diabetes, and to simulate the impact of controlling risk factors by 2030 in China. Methods: We simulated the burden of disease from diabetes in six scenarios according to the development goals of risk factors control by the WHO and Chinese government. Based on the theory of comparative risk assessment and the estimates of the burden of disease for China from the Global Burden of Disease Study 2015, we used the proportional change model to project the number of deaths, age-standardized mortality, and probability of premature mortality from diabetes under different scenarios of risk factors control in 2030. Results: If the trends in exposures to risk factors from 1990 to 2015 continued. Mortality, age-standardized mortality, and probability of premature mortality from diabetes would increase to 32.57/100 000, 17.32/100 000, and 0.84% by 2030, respectively. During that time, mortality, age-standardized mortality and probability of premature mortality for males would all be higher than for females. If the goals of controlling risk factors were all achieved, the number of deaths from diabetes in 2030 would decrease by 62.10% compared to the predicted numbers based on the historical trends in exposure to risk factors, and the probability of premature mortality would drop to 0.29%. If only the exposure to a single risk factor were achieved by 2030, high fasting plasma glucose control would have the greatest impact on diabetes, resulting in a 56.00% reduction in deaths compared to the predicted numbers based on the historical trends, followed by high BMI (4.92%), smoking (0.65%), and low physical activity (0.53%). Conclusions: Risk factors control plays an important role in reducing the number of deaths, age-standardized mortality rate, and probability of premature mortality from diabetes. We suggest taking comprehensive measures to control relevant risk factors for certain populations and regions, to achieve the goal of reducing the burden of disease from diabetes as expected.
Male ; Female ; Humans ; Risk Factors ; Diabetes Mellitus/epidemiology* ; Mortality, Premature ; Smoking ; Cost of Illness ; China/epidemiology* ; Global Burden of Disease

Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ² analysis, and a paired χ² test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ²=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ²=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ²=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ²=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ²=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Antiviral Agents/adverse effects* ; Esophageal and Gastric Varices/complications* ; Liver Cirrhosis/complications* ; Treatment Outcome ; Gastrointestinal Hemorrhage/complications* ; Hepatitis B/drug therapy*

Rheumatoid arthritis (RA) is an autoimmune disease driven by antigens and mediated by T cells. Collagen II (CII) and fibrinogen (Fib) are the two main antigens in the pathogenesis of RA. The antigen produced after citrulline modification (Cit) is also one of the inducements to induce the body to produce a pathogenic anti-citrulline protein antibody (ACPA). To provide a reference for RA-related research, this study intends to establish an RA animal model by using CII, Cit-CII, Fib, and Cit-Fib antigens, emulsification with complete Freund's adjuvant and immunization with DBA/1 mice, respectively, to compare the pathological characteristics of RA models induced by different antigens from the aspects of pathology, imaging and serum biochemistry. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of the China Academy of Chinese Medical Sciences. The results showed that the CII, Cit-CII, and Cit-Fib induced mice all had symptoms such as joint redness and swelling, and toe deformation and the clinical score and incidence rate were higher than those of the normal group. The CII group had the most serious lesions, with a incidence rate of 100%, and the Cit-CII and Cit-Fib groups had mild symptoms, with a incidence rate of 25% and 37.5%, respectively; pathological and imaging examination results showed that the joints of mice in CII-induced group showed severe synovial inflammation, cartilage and bone destruction, while those in Cit-CII and Cit-Fib group showed only slight inflammatory infiltration, joint cavity stenosis and bone destruction; the results of serum antibody detection showed that CII, Cit-CII and Cit-Fib groups all produced high levels of anti-cyclic citrullinated peptide (CCP) antibodies, among which, Cit-Fib group > Cit-CII group > CII group > Fib group, and both Cit-CII and Cit-Fib groups produced high levels of citrullinated epitope-specific antibodies, while the total IgG level was the highest in CII group; serum ELISA and RT-PCR analysis of joint tissue showed that the expression of pro-inflammatory factors and bone destruction-related molecules increased most significantly in the CII-induced group, followed by Cit-Fib and Cit-CII. The above results showed that among the four different antigens, the symptoms and conditions of arthritis in RA mice induced by CII were the most serious, and IgG instead of anti-CCP antibody was its typical immunological feature, and CII could be the first choice for the model of RA mice; Cit-Fib has certain immunogenicity, can partially induce the symptoms and conditions of RA arthritis in mice, and produce high-level anti-CCP antibody and anti-Cit-Fib antibody, which is more suitable for the study of citrulline-related RA; although Cit-CII has certain immunogenicity, the incidence, and severity of RA arthritis induced by Cit-CII in mice are low.

As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response. Consequently, adverse effects occur, such as autoimmunity, from the non-specific immune activation and non-specific inflammation in off-target organs. Nanocarriers that improve drug solubility, permeability, stability, bioavailability, as well as sustained, controlled, and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects. In particular, nanomedicine-based immunotherapy can be utilized to target tumor metastasis, presenting a promising therapeutic strategy for lung cancer. Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment; the breaking away of primary tumors, circulating tumor cell dissemination, and premetastatic niche formation cause distant secondary site colonization. In this review, we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer. We also discuss prospects for the emerging field and the clinical translation potential of these techniques.
Humans ; Lung Neoplasms/therapy* ; Tumor Microenvironment ; Neoplasms/drug therapy* ; Immunotherapy/methods*