Autoimmune pancreatitis is a special type of chronic pancreatitis that can lead to abnormal pancreatic exocrine function in patients. Autoimmune pancreatitis comorbid with pancreatic exocrine insufficiency has a complex pathogenesis， and there is limited research on this topic， leading to the lack of understanding of such patients in clinical practice. This article introduces the epidemiology of autoimmune pancreatitis， briefly describes the pathogenesis of pancreatic exocrine insufficiency caused by autoimmune pancreatitis， and summarizes the various detection methods for pancreatic exocrine function， nutritional assessments， lifestyle management， and drug therapy， in order to strengthen the understanding of autoimmune pancreatitis comorbid with pancreatic exocrine insufficiency and improve the clinical diagnosis and treatment of pancreatic exocrine insufficiency.

Objective To construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.Methods Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022,5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses(221 variables).According to the inclusion and exclusion criteria,4 097 couples were finally included,and randomly assigned into a training set(n=2 867 spouses)and a validation set(n=1 230 spouses)at a ratio of 7∶3.Feature analysis and collinear screening were applied to select the potential exposure factors.In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions,feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set.Five algorithms,that is,Logistic Regression,Naive Bayes,Random Forest,Gradient Boosting Machine,and Support Vector Machine,were used to construct preconception outcome prediction models,and the parameters of each model were optimized using random search combined with grid search.The predictive performance of each model was compared using precision,recall,F1 score,area under the receiver operating characteristic curve(AUC),and calibration curve.The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.Results There were 24 variables screened out in feature Set 1,and 16 variables in feature Set 2.In feature Set 1,the gradient boosting machine performed better,with a relatively higher AUC value(0.651)and better F1 score(0.61).The logistic regression model performed stably(AUC value=0.647)and was suitable as the reference model.The random forest(AUC value=0.641),Naive Bayes(AUC value=0.641),and support vector machine(AUC value=0.634)performed second-best.By utilizing the gradient boosting machine,comparable results were found between the predictions from feature sets with or without semen parameters,as in feature Set 1,the AUC value of its validation set was 0.651(95%CI:0.629～0.681),the prediction accuracy was 0.63,the recall rate was 0.65,and the average precision value F1 was 0.61;and in feature Set 2,the AUC value of its validation set was 0.649(95%CI:0.624～0.663),and both the calibration curves were close to the ideal curve.The prediction results indicated that in feature Set 1,the features highly negatively correlated with preconception outcomes were female age,male age,and no pregnancy within 1 year without contraception,while the features highly positively correlated with preconception outcomes were female pregnancy history,total sperm vitality,and use of contraceptive measures before enrollment.Conclusion Among the 5 machine-learning algorithms performed in this cohort data,the gradient boosting machine shows slightly better performance.There are 24 factors being associated with preconception outcomes in both spouses,and the performance of the simplified model excluding semen parameters is not significantly declined.It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

PI3Kγ and PI3Kδ have important regulatory roles in the immune system, and targeting these two subtypes helps to reshape the tumor microenvironment. PI3Kγ and PI3Kδ are potential targets for tumor immunotherapy. In this study, a series of new pyrazolopyrimidine derivatives were designed and synthesized on the basis of our previously reported PI3K inhibitors, resulting in the discovery of compound 16l as a potent and selective PI3Kγ/δ dual inhibitor. Compound 16l demonstrated strong biochemical potencies against PI3Kγ and PI3Kδ with IC₅₀ values of 0.11 and 0.79 nmol·L^-1. In cell-based assays, it potently inhibited the PI3Kγ and PI3Kδ mediated Akt S473 phosphorylation with EC₅₀ values of 3 and 7 nmol·L^-1. In vivo, compound 16l exhibited acceptable pharmacokinetic properties in Sprague-Dawley (SD) rats and suppressed the tumor growth in a MC38 syngeneic mouse model. The animal experiments were approved by the Animal Ethics Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (approval number: DWLL-2000-06). In addition, no appreciable human ether-a-go-go-related gene (hERG) inhibition was observed for compound 16l even at 30 μmol·L^-1. These results suggested that compound 16l might be a potential research tool for studying the PI3Kγ/δ mediated signaling pathways.

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Objective To analyze the bed utilization efficiency of various clinical departments in a public hospital and provide reference for the rational allocation of departmental bed resources.Methods Based on the data from a tertiary specialized hospital in 2022,traditional bed efficiency indicators were used as the basis.The Case Mix Index(CMI)was introduced for ad-justment,and the reasonable range of beds for each department was calculated.Data Envelopment Analysis(DEA)was em-ployed to comprehensively evaluate the input-output efficiency of each clinical department and determine the direction for optimi-zing bed allocation.Results Among the 39 departments included in the study,10 departments had inappropriate bed settings.Among them,5 departments needed additional beds,while 5 departments needed to reduce the number of beds.Conclusion By adjusting the bed efficiency indicators using CMI and combining the DEA method,hospitals can obtain a scientific basis for dy-namically adjusting the number of beds in clinical departments.Hospitals should make rational use of bed resources and scientifi-cally plan departmental beds.

Objective To investigate the effect of chronic psychological stress on testicular cell senescence in rats and the role of glucocorticoid receptor(GR)in the process.Methods Thirty-two male SD rats(4～6 weeks old,weighing 120～140 g)were randomly assigned into dimethyl sulfoxide(DMSO)group,mifepristone(RU486)group,chronic unpredictable mild stress(CUMS)group,and CUMS+RU486 group.DMSO of 0.5 ml/(kg·d)was injected subcutaneously into the rats of DMSO group.After the rats of the CUMS group were exposed to CUMS,mifepristone of 1 mg/(kg·d)was given to the rats of the RU486 group and CUMS+RU486 group.All the above 4 groups were inflicted for 42 consecutive days.After modeling,the psychological stress status of rats was evaluated with animal behavioral experiments.Computer-aided sperm analysis(CASA)system was used to detect sperm density.ELISA was employed to measure the serum levels of corticosterone(CORT),sex hormones and inflammation factors.The contents of malondialdehyde(MDA),H2O2,NAD+/NADH and ATP in the testicular tissues were tested with corresponding reagent kits.Western blotting was utilized to detect protein levels of[3-gal,p16,and GR in testicular tissue,and transmission electron microscopy was used to observe mitochondrial structure of spermatogenic cells.Results Compared with the DMSO group,the sperm density,serum levels of testosterone(T),luteinizing hormone(LH)and follicle stimulating hormone(FSH)were decreased while those of CORT and estradiol(E2)were increased in the CUMS group(all P＜0.001).Serum pro-inflammatory factors IL-6 and TNF-α concentrations were increased while anti-inflammatory factor IL-10 concentration was decreased in the CUMS group than the DMSO group(all P＜0.05).And,ATP content and NAD+/NADH ratio were decreased while MDA and H2O2 levels were elevated in testicular tissues in the CUMS group(all P＜0.05).Moreover,the protein levels of testicular cell aging markers β-gal,p16 and GR were significantly enhanced in the CUMS group(all P＜0.01),accompanied by swelling and vacuolization of mitochondrial structures in spermatogenic cells.RU486 treatment effectively improved sperm density and increased CORT level and down-regulated the testicularβ-gal,p16 and GR protein level(all P＜0.05).Conclusion Chronic psychological stress induces testicular damage in rats,presenting declines in sperm density and CORT level,which is possibly associated with GR-mediated cell senescence.

The intestinal absorption properties of the main effective components (glycyrrhizic acid, isoliquiritigenin, 6-gingerol, ginsenoside Rb1, atractylode-I) in Lizhong decoction (LZD) extracts were investigated with an in situ single-pass intestinal perfusion model in rats. UPLC-TQ-MS was used to determine the concentration of the five components in the intestinal perfusion. Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Nanjing University of Chinese Medicine. As evaluation indexes for the intestinal absorption characteristics, the absorption rate constant (K_a) and the apparent permeability coefficient (P_eff) of the five main ingredients were analyzed. Results showed that the best absorption sites for glycyrrhizic acid, isoliquiritin and 6-gingerol were the ileum, colon and duodenum, respectively, and the differences between different intestinal segments were statistically significant (P <0.05). There was no notable difference in K_a and P_eff between ginsenoside Rb1 and atractylode-I in the different intestinal segments (P > 0.05), suggesting that they were absorbed throughout. The five components were well-absorbed in the whole intestine (P_eff > 1.0×10^-3 cm·min^-1), indicating that LZD is suitable for preparing sustained, controlled release and enteric-coated preparations.

OBJECTIVES: This study aimed to investigate the common types and directions of root fractures of the maxillary first molar and the influence of root canal treatment on the prevalent sites of root fractures. METHODS: A total of 274 maxillary first molars with root fractures diagnosed via cone beam computed tomography were included. The root fractures of nonendodontically and endodontically treated teeth were identified to be spontaneous and secondary root fractures, respectively. The sites, types, and directions of spontaneous and secondary root fractures were determined. RESULTS: Among the spontaneous root fractures, the proportion of palatal root fractures (56.1%) was higher than those of mesial buccal root fractures (36.1%) and distal buccal root fractures (7.8%). Among the secondary root fractures, the proportion of mesial buccal root fractures (52.7%) was higher than those of palatal root fractures (36.5%) and distal buccal root fractures (10.8%). The distribution of predominant fracture sites was statistically significant ( CONCLUSIONS This study provided an epidemiological basis for the clinical features of root fractures of the maxillary first molar. During the dia-gnosis and treatment of the maxillary first molar, the possibility of palatal root fractures should be considered. The occurrence of mesial buccal root fractures may be related to root canal treatment. Therefore, the risk of mesial buccal root fractures caused by iatrogenic factors should be minimized.
Cone-Beam Computed Tomography ; Humans ; Molar ; Root Canal Therapy ; Tooth Root ; Tooth, Nonvital

OBJECTIVE: To observe the changes of functional connectivity of brain pain-emotion regulation region in patients with cervical spondylosis of cervical type by functional magnetic resonance imaging (fMRI). METHODS: Thirty-two subjects were selected. Of them, 16 patients with cervical spondylosis of cervical type were divided into an observation group and 16 healthy subjects into a control group. The patients in the observation group were treated with acupuncture at Tianzhu (BL 10), Jingbailao (EX-HN 15), Jianzhongshu (SI 15) and RESULTS: In the observation group, the VAS score was (1.94±1.12) after the treatment, which was lower than (5.62±1.20) before treatment ( CONCLUSION Pain involves the formation and expression of "pain-emotion-cognition". Acupuncture can systematically regulate the brain functional connections between cognitive regions such as dorsal prefrontal lobe and anterior cingulate gyrus and emotional regions such as insula and VTA in patients with cervical spondylosis of cervical type, suggesting that acupuncture has a multi-dimensional and comprehensive regulation effect on pain.
Acupuncture Therapy ; Brain/diagnostic imaging* ; Emotions ; Humans ; Magnetic Resonance Imaging ; Pain ; Spondylosis/therapy*

OBJECTIVE: To study the association of platelet level at diagnosis with prognosis in children with acute lymphoblastic leukemia (ALL). METHODS: A total of 892 children with ALL who underwent chemotherapy with the CCLG-ALL 2008 regimen were enrolled. According to the platelet count at diagnosis, these children were divided into normal platelet count group (platelet count ≥100×109/L; n=263) and thrombocytopenia group (platelet count <100×10/L; n=629). The thrombocytopenia group was further divided into (50- <100)×10/L (n=243), (20- <50)×10/L (n=263), and <20×10/L (n=123) subgroups. The association of clinical features (sex, age, immunophenotype, and molecular biology) with event-free survival (EFS) and overall survival (OS) was analyzed. RESULTS: Compared with the thrombocytopenia group, the normal platelet count group had significantly lower positive rate of MLL gene rearrangement and recurrence rate (P<0.05), as well as a significantly higher 10-year EFS rate (P<0.05). There was no significant difference in 10-year OS between the two groups (P>0.05). The normal platelet count group still had a significantly higher 10-year EFS rate than the thrombocytopenia group after the children with MLL gene rearrangement were excluded (P<0.05), and there was still no significant difference in 10-year OS between the two groups (P>0.05). The <20×10/L subgroup had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50- <100)×10/L subgroup, and the (20- <50)×10/L subgroup (P<0.05). After the children with MLL gene rearrangement were excluded, the <20×10/L subgroup still had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50-<100)×10/L subgroup, and the (20- <50)×10/L subgroup (P<0.05). CONCLUSIONS ALL children with MLL gene rearrangement often have the clinical manifestation of thrombocytopenia. Platelet level at diagnosis is associated with the prognosis of ALL children. The children with normal platelet count have a low recurrence rate and good prognosis, and those with a platelet count of <20×10/L have the worst prognosis.
Child ; Disease-Free Survival ; Humans ; Immunophenotyping ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence