ObjectiveTo investigate the features and mechanism of action of intestinal flora in patients with nonalcoholic fatty liver disease （NAFLD） and Helicobacter pylori （HP） infection by comparing the changes in intestinal flora between the healthy population， the patients with HP infection， the patients with NAFLD， and the patients with NAFLD and HP infection. MethodsThis study was conducted among the 19 patients with NAFLD （NAFLD group）， 19 patients with HP infection （HP group）， and 19 patients with NAFLD and HP infection （NAFLD+HP group） who were admitted to The Second Affiliated Hospital of Henan University of Science and Technology from March 1， 2023 to April 30， 2024， and 20 individuals undergoing physical examination were enrolled as control group. Fecal samples were collected， total DNA was extracted for PCR amplification， and 16S rDNA sequencing was performed to compare the features of intestinal flora between the four groups. An analysis of variance was used for comparison of continuous data between multiple groups， and the chi-square test was used for comparison of categorical data between multiple groups. The Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of the species in intestinal flora. ResultsThe NAFLD+HP group showed a tendency of reduction in flora abundance compared with the other three groups. There was a significant difference in flora distribution between the NAFLD+HP group and the NAFLD group and between the NAFLD group and the control group （P<0.05）. At the phylum level， the top three species in the NAFLD+HP group were Firmicutes （59.94%）， Proteobacteria （17.00%）， and Actinobacteria （14.75%）， with an increase in the proportion of Proteobacteria and a reduction in the proportion of Actinobacteria compared with the other three groups. At the genus level， the top five dominant bacteria in the NAFLD+HP group were Bifidobacterium， Streptococcus， Escherichia-Shigella， Agathobacter， and Ruminococcus gnavus_group. Compared with the NAFLD group， the NAFLD+HP group had increases in the abundance of Streptococcus， Veillonella， and Rothia and reductions in the abundance of Dialister and Ruminococcus toraues_group. Compared with the HP group， the NAFLD+HP group had reductions in the abundance of Collinsella， Subdoligranulum， Catenibacterium， and Porphyromonas and increases in the abundance of Citrobacter and Olsenella （all P<0.05）. ConclusionPatients with NAFLD and HP infection have changed in intestinal flora. These flora may be the intestinal microecological factors for HP infection in promoting the development and progression of NAFLD.

Objective: To analyze the epidemiological characteristics and incidence trends of pulmonary tuberculosis (TB) in children aged 0-14 years in Shaanxi Province from 2010 to 2024, so as to provide a reference for optimizing child TB prevention and control strategies. Methods: Data on pulmonary TB cases in children aged 0-14 years and demographic information in Shaanxi Province from 2010 to 2024 were collected from Surveillance and Reporting Management System with Disease Prevention and Control Information Management System under the National Health Security Informatization Project Disease Prevention and Control Information System. A Joinpoint regression model was established to analyze the temporal, spatial, and population distribution trends of child pulmonary TB incidence. Results: A total of 2 954 cases of pulmonary TB in children aged 0-14 years were reported in Shaanxi Province from 2010 to 2024, accounting for 0.97% of all TB cases in the general population. The average annual reported incidence rate in children was 3.32 per 100 000. Among these cases, 804 were pathogenetically positive, showing a increasing trend ( χ 2 trend =420.94, P < 0.01 ). The overall reported incidence rate of pulmonary TB in children aged 0-14 years in Shaanxi Province showed a decreasing trend, dropping from 5.35 per 100 000 in 2010 to 2.41 per 100 000 in 2024. Joinpoint regression analysis identified three distinct phases for the reported incidence rate of TB:a rapid decline from 2010 to 2013 (APC=-20.02%, 95% CI = -33.64% to -10.42%), a slight increase from 2013 to 2017 (APC=11.18%, 95% CI =3.07%-24.17%) and a slight decline again from 2017 to 2024 (APC= -7.27 %, 95% CI =-12.73% to -4.30%) (all P <0.01). Among children aged 0-14 years, the age group with the highest average annual reported incidence rate was 10-14 years (8.02 per 100 000), followed by 5-9 years (1.44 per 100 000), and 0-4 years had the lowest rate (0.95 per 100 000). The difference in reported incidence rates among the three age groups was statistically significant ( χ 2= 51.91, P <0.01). The average annual reported incidence rate of TB was 3.25 per 100 000 in boys and 3.39 per 100 000 in girls, with no statistically significant difference ( χ 2=2.01, P >0.05). There was no obvious periodic variation in the annual case reporting. Among all cities in Shaanxi Province, Ankang City had the highest average annual reported incidence rate (5.16 per 100 000). Conclusions From 2010 to 2024, the reported incidence rate of pulmonary TB in children aged 0-14 years in Shaanxi Province showed an overall decreasing trend. However, it is still necessary to strengthen active surveillance, implement targeted measures in high incidence areas such as Ankang City, and maintain continuous attention to child TB prevention and control.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

PURPOSE: Traumatic brain injury (TBI) is a significant public health issue that impacts individuals all over the world and is one of the main causes of mortality and morbidity. Decompressive craniectomy is the usual course of treatment. Basal cisternostomy has been shown to be highly effective as an alternative procedure to decompressive craniectomy. METHODS: We conducted a retrospective cohort of patients who received surgery for severe TBI between January 2019 and March 2023. Inclusion criterias were patients between the ages of 18 and 70 years who met the diagnostic criteria for severe TBI at first presentation and who underwent surgical intervention. The exclusion criteria were patients who have severe multiple injuries at the time of admission; preoperative intracranial pressure > 60 mmHg; cognitive impairment before the onset of the disease; hematologic disorders; or impaired functioning of the heart, liver, kidneys, or other visceral organs. Depending on the surgical approach, the patients were categorized into decompressive craniectomy group as well as basal cisternostomy group. General data and postoperative indicators, including Glasgow coma scale, intracranial pressure, etc., were recorded for both groups of patients. Among them, the Glasgow outcome scale extended assessment at 6 months served as the primary outcome. After that, the data were statistically analyzed using SPSS software. RESULTS: The trial enrolled 41 patients (32 men and 9 women) who met the inclusion criteria. Among them, 25 patients received decompressive decompressive craniectomy, and 16 patients received basal cisternostomy. Three days postoperative intracranial pressure levels were 10.07 ± 2.94 mmHg and 17.15 ± 14.65 mmHg (p = 0.013), respectively. The 6 months following discharge Glasgow outcome scale extended of patients was 4.73 ± 2.28 and 3.14 ± 2.15 (p = 0.027), respectively. CONCLUSION Our study reveals that basal cisternostomy in patients with surgically treated severe TBI has demonstrated significant efficacy in reducing intracranial pressure as well as patient prognosis follow-up and avoids removal of the bone flap. The efficacy of cisternostomy has to be studied in larger, multi-clinical center randomized trials.
Humans ; Brain Injuries, Traumatic/surgery* ; Retrospective Studies ; Male ; Female ; Adult ; Middle Aged ; Decompressive Craniectomy/methods* ; Aged ; Young Adult ; Adolescent ; Glasgow Coma Scale ; Treatment Outcome

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

OBJECTIVE: To explore the correlation between mechanical power normalized to dynamic lung compliance (Cdyn-MP) and weaning outcomes and prognosis in mechanically ventilated patients. METHODS: A prospective, observational cohort study was conducted. Patients who underwent invasive mechanical ventilation (IMV) for more than 24 hours and used a T-tube ventilation strategy for extubation in the intensive care unit (ICU) of Lianyungang First People's Hospital and Lianyungang Second People's Hospital between January 2022 and December 2023 were enrolled. The collected data encompassed patients' baseline characteristics, primary causes of ICU admission, vital signs and laboratory indicators during the initial spontaneous breathing trial (SBT), respiratory mechanics parameters within the 4-hour period prior to the SBT, weaning outcomes and prognostic indicators. Mechanical power (MP) and Cdyn-MP were calculated using a simplified MP equation. Univariate and multivariate Logistic regression analyses were utilized to determine the independent risk factors associated with weaning failure in patients undergoing mechanical ventilation. Restricted cubic spline (RCS) analysis and Spearman rank-sum test were employed to investigate the correlation between Cdyn-MP and weaning outcomes as well as prognosis. Receiver operator characteristic curve (ROC curve) was constructed, and the area under the ROC curve (AUC) was computed to evaluate the predictive accuracy of Cdyn-MP for weaning outcomes in mechanically ventilated patients. RESULTS: A total of 366 patients undergoing IMV were enrolled in this study, with 243 cases classified as successful weaning and 123 cases classified as failed weaning. Among them, 23 patients underwent re-intubation within 48 hours after the successful withdrawal of the first SBT, non-invasive ventilation, or died. Compared with the successful weaning group, the patients in the failed weaning group had significantly increased levels of sequential organ failure assessment (SOFA) score, body temperature and respiratory rate (RR) during SBT, and respiratory mechanical parameters within the 4-hour period prior to the SBT [ventilation frequency, positive end-expiratory pressure (PEEP), platform pressure (Pplat), peak inspiratory pressure (Ppeak), dynamic driving pressure (ΔPaw), fraction of inspired oxygen (FiO₂), MP, and Cdyn-MP], dynamic lung compliance (Cdyn) was significantly reduced, and duration of IMV, ICU length of stay, and total length of hospital stay were significantly prolonged. However, there were no statistically significant differences in age, gender, body mass index (BMI), smoking history, main causes of ICU admission, other vital signs [heart rate (HR), mean arterial pressure (MAP), saturation of peripheral oxygen (SpO₂)] and laboratory indicators [white blood cell count (WBC), albumin (Alb), serum creatinine (SCr)] during SBT of patients between the two groups. Univariate Logistic regression analysis was conducted, and variables with P < 0.05 and no multicollinearity with Cdyn-MP were selected for inclusion in the multivariate Logistic regression model. The results demonstrated that SOFA score [odds ratio (OR) = 1.081, 95% confidence interval (95%CI) was 1.008-1.160, P = 0.030], and PEEP (OR = 1.191, 95%CI was 1.075-1.329, P = 0.001), FiO₂ (OR = 1.035, 95%CI was 1.006-1.068, P = 0.021) and Cdyn-MP (OR = 1.190, 95%CI was 1.086-1.309, P < 0.001) within the 4-hour period prior to the SBT were independent risk factors for weaning failure in patients undergoing IMV. The RCS analysis after adjusting for confounding factors showed that as Cdyn-MP within the 4-hour period prior to the SBT increased, the risk of weaning failure in patients undergoing IMV significantly increased (P < 0.001). The Spearman rank correlation test showed that Cdyn-MP within the 4-hour period prior to the SBT was positively correlated with respiratory mechanical parameters including ΔPaw and MP (r values were 0.773 and 0.865, both P < 0.01), and negatively correlated with Cdyn (r = -0.587, P < 0.01). Cdyn-MP within the 4-hour period prior to the SBT was positively correlated with prognostic indicators such as duration of IMV, length of ICU stay, and total length of hospital stay (r values were 0.295, 0.196, and 0.120, all P < 0.05). ROC curve analysis demonstrated that, within the 4-hour period preceding the SBT, Cdyn-MP, MP, Cdyn, and ΔPaw possessed predictive value for weaning failure in patients undergoing IMV. Notably, Cdyn-MP exhibited superior predictive capability, evidenced by an AUC of 0.761, with a 95%CI ranging from 0.712 to 0.810 (P < 0.001). At the optimal cut-off value of 408.5 J/min×cmH₂O/mL×10^-3, the sensitivity was 68.29%, and the specificity was 71.19%. CONCLUSION Cdyn-MP is related to weaning outcomes and prognosis in mechanically ventilated patients, and has good predictive ability in assessing the risk of weaning failure.
Humans ; Prospective Studies ; Ventilator Weaning ; Prognosis ; Respiration, Artificial ; Intensive Care Units ; Lung Compliance ; Female ; Male ; Middle Aged ; Aged

Objective To investigate the liver disease phenotypes and clinical features of patients with different genotypes of Wilson's disease(WD).Methods A retrospective analysis was performed for 163 patients with WD who were diagnosed and underwent genetic testing in The Fifth Medical Center of Chinese PLA General Hospital from August 2008 to June 2023,and clinical manifestations,laboratory examination,pathological examination,imaging examination,and ATP7B genetic testing results were collected.According to ATP7B gene mutation,the patients were divided into groups as follows:R778L mutation group and non-R778L mutation group;P992L mutation group and non-P992L mutation group;truncation mutation group and non-truncation mutation group.Liver disease phenotypes and clinical features were analyzed for the patients with c.2333G>T/p.R778L mutation(R778L mutation),c.2975C>T/p.P992L mutation(P992L mutation),and truncation mutation of the ATP7B gene.The Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of continuous data between groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results The 163 patients with WD had varying severities of liver disease phenotypes,among whom 121(74.23%)were diagnosed with chronic liver disease,36(22.09%)were diagnosed with decompensated cirrhosis,and 6(3.68%)were diagnosed with fulminant WD,and in addition,there were 5 patients(2 with chronic liver disease and 3 with decompensated cirrhosis)with neurological abnormalities.For the 163 patients with WD,R778L mutation(with an allele frequency of 28.2%)was the most common mutation in the ATP7B gene,followed by P992L mutation(with an allele frequency of 12.6%),and truncation mutation showed an allele frequency of 11.0%.There was no significant difference in the distribution of the three mutations across different liver disease phenotypes(P>0.05).The R778L mutation group had a significantly lower level of ceruloplasmin(CP)than the non-R778L mutation group[0.04(0.02-0.08)g/L vs 0.08(0.03-0.13)g/L,Z=-2.889,P=0.004].Compared with the non-P992L mutation group,the P992L mutation group had significantly higher levels of alanine aminotransferase[135.0(80.5-237.0)U/L vs 80.5(36.0-173.3)U/L,Z=2.684,P=0.007]and aspartate aminotransferase[121.4(77.0-195.0)U/L vs 84.0(39.0-123.3)U/L,Z=3.388,P<0.001].Compared with the non-truncation mutation group,the truncation mutation group had significantly lower levels of CP[0.03(0.02-0.08)g/L vs 0.06(0.03-0.11)g/L,Z=-3.136,P=0.002]and serum copper[3.20(2.15-5.00)mg/L vs 4.20(2.60-7.50)mg/L,Z=-2.296,P=0.025].Conclusion R778L mutation,P992L mutation and truncation mutation are not associated with liver disease phenotype in WD patients;however,R778L mutation is associated with a lower level of CP,P992L mutation is associated with higher levels of ALT and AST,and truncation mutation is associated with lower levels of CP and serum copper.

Objective:To determine the karyotype of a patient with mosaicism complex structural aberration of chromosome 18.Methods:A male patient with a 2-year history of infertility presented at the Center of Reproductive Medicine of the Third Hospital of Peking University in October 2019 was selected as the study subject. Clinical data of the patient was collected. Peripheral blood sample was taken for chromosomal karyotyping, copy number variation (CNV) analysis and fluorescence in situ hybridization (FISH) assay. Semen sample was taken for single sperm CNV analysis. Results:The patient was found to have a karyotype of mos 47, XY, del(18)(q21q23), + r(18)(q21q23)[84]/46, XY, del(18)(q21q23)[9]/48, XY, del(18)(q21q23), + r(18)(q21q23)×2[6]/47, XY, del(18)(q21q23), + r(18)(q21q23×2)[1]. ish 47, XY, del(18)(q21q23), + r(18)(q21q23)[84]/46, XY, del(18)(q21q23)[9]/48, XY, del(18)(q21q23), + r(18)(q21q23)×2[6]/47, XY, del(18)(q21q23), + r(18)(q21q23×2)[1]del(18)(q21q23)( D18Z1+, 18p+, 18q+, WCP18+ ), r(18)(q21q23)(WCP18+ ), r(18)(q21q23×2)(WCP18+ ). No pathogenic CNV was identified. Sequencing of 20 single sperms showed that 1 sperm was normal, 1 had yielded no result, 9 had harbored del(18q), 7 had harbored dup(18q)×2, and 2 had harbored dup(18q)×3. The dup/del fragments had both spanned approximately 33 Mb. Conclusion:It is rare for carriers of complex structural and numerical abnormalities of chromosome 18 to have a normal phenotype. Based on the accurate cytogenetic and molecular analyses and the single sperm CNV analysis, the influence of the aberrant karyotype on the gametogenesis may be evaluated.

OBJECTIVE To establish a method for determining the content of 11 antioxidants and their degradation products in recombinant Exendin-4-FC fusion protein injection by HPLC. METHODS The protein was precipitated with saturated ammonium sulfate. After centrifugation, the supernatant was transferred to a C18 solid phase extraction cartridge activated by methanol. Then the cartridge was eluted with 4 mL of methanol and 5 mL of ethyl acetate respectively, and the eluent was diluted with methanol-ethyl acetate(2∶3) mixed solvent and passed through a 0.22 µm PTFE hydrophobic filter. It was analyzed by HPLC and quantified by external standard method. Chromatographic conditions: Kinetex® XB-C18 100Å (100 mm×4.6 mm, 2.6 µm)column, the detection wavelength was 230 nm, the column oven was 30 ℃, the injection volume was 5 µL and the flow rate was 0.4 mL·min–1, mobile phase was 0.1% formic acid-methanol(A)-0.1% formic acid aqueous solution(B), the running time was 45 min. RESULTS The 11 target substances showed a good linear relationship in the range of 2.5−35 μg·mL–1 with R2 ≥0.99. At three different concentration(25, 10, 5 μg·mL–1) of spiked samples, the average recovery rates of 11 antioxidants ranged from 88.1% to 106.5%, with RSDs in the range of 0.10%–9.05%. The RSDs of 6 repeatable samples was 2.01%–4.77%, which of 12 intermediate precision samples was 2.58%–9.75%. The positive/inverted samples of three batches of recombinant Exendin-4-FC fusion protein injection were detected at 0 month, 3 months and 6 months(25 ℃), and the results showed that there was no antioxidant and its degradation leaching in all batches of samples at different detection points. CONCLUSION The method has good specificity, high accuracy and precision, good solution stability, high durability and can be used for the content detection of antioxidants in drugs.