The clinical data of 10 patients with pathologically confirmed primary hepatic neuroendocrine neoplasms (PHNENs) were retrospectively analyzed. The cohort included 8 males and 2 females, with a median age of 63 years. None presented with carcinoid syndrome. Three cases were detected incidentally during health check-ups, 2 presented with painless jaundice, and 5 reported abdominal distension or pain (1 with concurrent jaundice). Elevated tumor markers included carbohydrate antigen 19-9 in 4 cases, alpha-fetoprotein in 2 cases, and neuron-specific enolase in 1 case. All patients underwent surgical resection, including hepatectomy and hilar cholangiocarcinoma resection, combining with resection and reconstruction of right hepatic artery, resection of liver metastases and pancreaticoduodenectomy according to the extent of tumor invasion.Preoperative imaging failed to diagnose neuroendocrine neoplasms in all cases. Final pathological diagnoses were neuroendocrine tumor (NET) G2 in 5 cases, NET G3 in 1 case, and neuroendocrine carcinoma (NEC) in 4 cases. During the follow-up, 4 patients died and 6 survived. The study demonstrates that PHNENs lack specific clinical or imaging features, and the diagnosis relies on pathological examination after excluding metastatic disease. Radical resection remains the primary treatment, with prognosis varying significantly by tumor grade.
Humans ; Middle Aged ; Male ; Female ; Neuroendocrine Tumors/pathology* ; Liver Neoplasms/pathology* ; Retrospective Studies ; Aged ; Adult

Various therapeuti modailities have been engineered for lung cancer treatment, but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment. Herein, we fabricated a library of small molecule redox-labile nanoparticles (NPs) (i.e., diPTX-2C NPs, diPTX-2S NPs, and diPTX-2Se NPs) by the self-assembly of dimer paclitaxel (PTX) prodrug, and then utilized these NPs with the traditional Chinese medicine (TCM) Qi-Yu-San-Long-Fang (Q) for effective chemoimmunotherapy on Lewis lung carcinoma (LLC)-bearing mice models. Under the high concentration of glutathione (GSH) and H₂O₂, diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells. In LLC tumor-bearing mice, oral administration of Q not only effectively downregulated programmed death ligand-1 (PD-L1) expression, but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4⁺ T and CD8⁺ T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues, collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs. Besides, we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models. This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective:To evaluate the clinical efficacy and safety of Blinatumomab on the treatment of refractory or relapsed precursor B-cell acute lymphoblastic leukemia (R/R BCP-ALL) in children.Methods:Clinical data of children with R/R BCP-ALL treated with Blinatumomab in the Department of Hematology, Children′s Hospital of Soochow University, from August 2021 to June 2022 were retrospectively analyzed.Children were divided into<45 kg group and ≥45 kg group according to their weight at admission.They were treated with different dosages of Blinatumomab, and bone marrow remission was assessed at about 15 days.Clinical indicators and adverse events during the treatment period were recorded.The rank sum test of two independent samples were used to compare the differences between groups.The Fisher′ s test was used for comparing categorical variables. Results:Among the 16 children with R/R BCP-ALL, 12 cases (75%) achieved complete response (CR) and minimal residual lesion (MRD) turned negative at about 14 days.Among them, 5 out of 9 children with bone marrow primitive naive cell ratio≥0.5 achieved CR, and 7/7 children with bone marrow primitive naive cell ratio<0.5 achieved CR.The peak value of interleukin-6 (IL-6) in children with CR was significantly higher than those without CR ( Z=2.50, P=0.012). Twelve cases achieved CR on bone marrow assessment around day 15, and 3 cases who did not achieve CR remained in remission on day 28, with an efficacy prediction accuracy of 93.8%(15/16). Adverse events included fever, neutropenia, hypokalemia, abnormal liver function, hypocalcemia, edema, rash, hypertension, myocardial damage, abdominal pain, hypotension, and cytokine release syndrome, which were all grade 1.Neurotoxicity and death were not reported. Conclusions:The remission rate of R/R BCP-ALL in children treated with Blinatumomab was high, especially in patients with a low tumor load.The toxicity and adverse events of Blinatumomab treatment are minor and controllable.Day 15 is the optimal time point to evaluate the efficacy of Blinatumomab on children with R/R BCP-ALL, and a higher IL-6 peak can be served as a predictor of its efficacy.

Abstract OBJECTIVE To establish a detection method for fingerprints and content determination of free sugar and hydrolyzed monosaccharide of intracellular glycopeptides in Coriolus versicolor. METHODS PMP derivatization after ultrasonic extraction with water as solvent was determined for free sugars, and PMP derivatization after acid hydrolysis was determined for hydrolyzed monosaccharides. The free sugars and hydrolyzed monosaccharides of raw materials and intermediates of intracellular glycopeptides from different manufacturers were analyzed by HPLC qualitatively and quantitatively. The fingerprints were analyzed by chemometrics analysis, and the differences between intracellular glycopeptides produced by different manufacturers were discussed. RESULTS Both two methods were validated by methodology. The samples from different manufacturers were clustered separately, and three free sugars and two hydrolyzed monosaccharides contributed greatly to the quality difference of intracellular glycopeptides of Coriolus versicolor. CONCLUSION The established analytical method can be effectively used for the determination of free sugars and hydrolyzed monosaccharides in the intracellular glycopeptide of Coriolus versicolor and the study of fingerprints. The adopted chemometrics research method provides guidance for the quality control of the intracellular glycopeptide of Coriolus versicolor.

Objective:To explore the correlation between lean nonalcoholic fatty liver disease (NAFLD) and metabolic indicators in a young and middle-aged population undergoing physical examination.Methods:It was a cross-sectional study. A total of 8 250 individuals who underwent routine physical examinations at the Health Medical Center of the Second Affiliated Hospital of Chongqing Medical University from January to December 2021 and met the inclusion and exclusion criteria were selected as the research subbjects. The general examination, fasting blood glucose, blood lipids, liver function, renal function, and fasting color ultrasound examination results were analyzed retrospectively to assess the correlation between lean NAFLD and major metabolic indicators using independent sample t-test, chi-square test, and multivariable logistic regression. Results:The prevalence of lean NAFLD was higher in men than in women (50.7% vs. 49.3%, χ2=97.261, P<0.001). After stratifying the age of onset of lean NAFLD, the peak age of onset was found to be between 45 and 59 years, with the prevalence gradually increasing with age. When stratified by body mass index (BMI), the peak incidence of lean NAFLD was observed in individuals with a BMI of ≥20 and <23 kg/m 2, with the prevalence showing a significant upward trend as BMI increased. The systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, low-density lipoprotein, fasting blood glucose, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, and serum uric acid in lean NAFLD groupwere all significantly higher than those in lean non-NAFLD group (all P<0.01), and the level of high density lipoprotein was significantly lower than that of lean non-NAFLD group ( t=23.755, P<0.001). The logistic analysis showed that systolic blood pressure ( OR=1.258, 95% CI: 1.081-1.465), diastolic blood pressure ( OR=1.282, 95% CI: 1.056-1.557), total cholesterol ( OR=1.712, 95% CI: 1.525-1.923), triglyceride ( OR=4.115, 95% CI: 3.621-4.676), alanine aminotransferase ( OR=1.467, 95% CI: 1.104-1.950), γ-glutamyltransferase ( OR=1.482, 95% CI: 1.242-1.769), fasting blood glucose ( OR=2.479, 95% CI: 2.092-2.939) and serum uric acid ( OR=1.390, 95% CI: 1.236-1.563) were independent metabolic risk factors for lean NAFLD (all P<0.05). Conclusions:The levels of various metabolic markers in young and middle-aged patients with lean NAFLD increase, and the risk of lean NAFLD increases. Metabolic markers are helpful to screen people at risk of lean NAFLD.

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R² = 0.033; P = 0.018), followed by acute kidney injury (AKI; R² = 0.032; P = 0.011) and plasma MIP-1β level (R² = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
Acute Kidney Injury/complications* ; Bacteria/classification* ; Chemokine CCL4/blood* ; Community-Acquired Infections/microbiology* ; Humans ; Lung ; Microbiota/genetics* ; Pneumonia, Bacterial/diagnosis* ; Prognosis ; RNA, Ribosomal, 16S/genetics*

BACKGROUND:The Y-shaped mesh graft material weaved using lightweight polypropylen has the appropriate porosity, which not only can make the vaginal tissues grow and fuse rapidly on the mesh, but also can maintain good biological strength to ensure the fixed strength for the presacral suspension. OBJECTIVE:To retrospectively analyze the clinical effect of Y-shaped mesh for the biological function reconstruction of the female pelvic floor. METHODS:Ten female cases of pelvic floor dysfunction were enrol ed, aged 37-73 years, and al were given the treatment of sacral colposuspension under laparoscopy. Then perioperative complications were recorded;patients were fol owed up regularly to record the Pelvic Organ Prolapse Quantification (POP-Q) score at different time points;and the subjective satisfaction was investigated using the Pelvic Floor Impact Questionnaire (PFIQ-7). RESULTS AND CONCLUSION:After at least 6-month fol ow-up, no postoperative pelvic infection, nerve damage and complications appeared, the patients healed wel , and no mesh erosion, infection and other adverse reactions occurred. The POP-Q and PFIQ-7 scores at 1, 3 and 6 months after repair were significantly improved than those before repair (P<0.05). These results suggest that the Y-shaped biological mesh repairing female midpelvic floor dysfunction has good biocompatibility, and can restore the anatomy of the pelvic floor.

Objective To estabhsh a set of consummate evaluation methods of animal models which are with syndromes of Traditional Chinese Medicine.Methods By means of Streptococcus pneumoniae-induced pyretic pulmonary syndrome model for the entry point,in the base of the conventional evaluation methods,further attempt were made through metabonomies,through analyzing metabolic fingerprint data of rats'urine in the control group together with the model group and metabolome of rats'urine in model group at different times,in order to approach the evaluation methods of animal models.Results After rats were given Streptococctts pneumoniae through nose,compared with the control group,both the body temperature variance and lencocyte count in model group were statistically significant with P <0.01,pathological changes of lung was obvious;According to the metabolic results,metabolic profiles of rats'urine in model group changed and metabolome diverged obviously in scores plot,the research results of metabonomics were coincide with the results of macroscopy physical sign and pathological biochemistry of Pyrefic pulmonary syndrome.Conclusion Metabonomics can be used to evaluate the studies of animal models with syndromes of traditional Chinese medieine.