ObjectiveTo investigate the risk factors for pyogenic liver abscess （PLA） comorbid with sepsis by analyzing clinical features， and to construct a predictive model. MethodsA retrospective analysis was performed for 489 patients who were hospitalized and diagnosed with PLA in The Affiliated Hospital of Xuzhou Medical University from January 2019 to December 2023， and according to the presence or absence of sepsis， they were divided into sepsis group with 306 patients and non-sepsis group with 183 patients. Related data were collected， including general information， laboratory markers， and outcome measures. The patients were further divided into a training set of 342 patients and a validation set of 147 patients at a ratio of 7∶3， and the training set was used for screening of variables and construction of a predictive model， while the validation set was used to test the performance of the model. An LASSO regression analysis was used for the screening of variables， and a multivariate Logistic regression analysis was used to construct the predictive model and plot a nomogram. The calibration curve， the receiver operating characteristic （ROC） curve， and the decision curve analysis were used for the validation of the model， and internal validation was performed for assessment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical variables between groups. ResultsThere were significant differences between the sepsis group and the non-sepsis group in pulse rate， mean arterial pressure， duration pf symptoms， comorbidity of liver cirrhosis or malignant tumor， leukocyte count， neutrophil count， lymphocyte count， platelet count （PLT）， activated partial thromboplastin time， fibrinogen， C-reactive protein， aspartate aminotransferase， alanine aminotransferase， albumin， total bilirubin （TBil）， creatinine， potassium， and prognostic nutritional index （PNI） （all P<0.05）. In the training set， the LASSO regression analysis identified four predictive factors of pulse rate， PLT， TBil and PNI， and the multivariate Logistic regression analysis showed that pulse rate （odds ratio ［OR］=1.033， 95% confidence interval ［CI］： 1.006‍ ‍—‍ ‍1.061， P=0.018）， PLT （OR=0.981， 95%CI： 0.975‍ ‍—‍ ‍0.987， P<0.001）， TBil （OR=1.086， 95%CI： 1.053‍ ‍—‍ ‍1.125， P<0.001）， and PNI （OR=0.935， 95%CI： 0.882‍ ‍—‍ ‍0.988， P=0.019） were independent influencing factors for the risk of sepsis in patients with PLA. The model constructed based on these factors showed a good predictive ability， with an area under the ROC curve of 0.948 （95%CI： 0.923‍ ‍—‍ ‍0.973） in the training set and 0.912 （95%CI： 0.848‍ ‍—‍ ‍0.976） in the validation set. The decision curve analysis showed that the model has a good net benefit within the range of 0.3‍ ‍—‍ ‍0.9 for threshold probability. ConclusionThe nomogram prediction model constructed based on pulse rate， PLT， TBil， and PNI has a certain clinical value and can well predict the risk of sepsis in patients with PLA.

Objective:To conduct the genetic analysis of a family with one patient suffering from juvenile Parkinson's disease(JP)and discuss the clinical manifestations,genetic mutation characteristics,and treatment plans prompted by PRKN gene compound heterozygous mutations,and to enhance the clinicians'awareness of this disease.Methods:The clinical data of one patient with JP caused by PRKN gene mutations was analyzed,the clinical manifestations and genetic mutation features of the patient were summarized,and the related literatures were reviewed.Results:The patient,a 16-year-old male,was admitted to the hospital due to unstable gait,trembling limbs with rigidity in both lower limbs for three years.The examination results revealed a panic gait,clear consciousness,fluent speech,normal muscle strength in limbs,increased"gear-like"muscle tone in both upper limbs,and"lead-pipe"rigidity in both lower limbs;the sensory functions and tendon reflexes were normal.The head,neck,and thoracic magnetic resonance imaging(MRI)results showed no abnormalities.18F-fluorodeoxyglucose(18F-FDG)positron emission tomography/computed tomography(PET/CT)results showed that the head size and shape were normal,the glucose metabolism in the left cerebellum and middle temporal gyrus was slightly decreased,and the glucose metabolism in bilateral thalami,right frontal lobe,parietotemporal lobe,and left medial frontal lobe was increased.The dopamine transporter(DAT)PET/CT results showed that there was no radioactive distribution in the brain cortex and the DAT distribution in the posterior part of both striata was decreased.The whole-exome sequencing results showed the patient had two PRKN gene mutations,such as codons c.8T>A and c.850G>C compound heterozygous mutations,and each mutation was from one parent;the patient's father carried the c.8T>A mutation,the patient's mother carried the c.850G>C mutation,and the patient's sister had the same genetic mutation site as the patient's father.Conclusion:PRKN gene compound heterozygous mutations may be the basis of the disease in this family.Identification of the mutation c.8T>A expands the mutation spectrum of the PRKN gene,and provides the valuable information for the research on the pathogenic genetic mutations of the JP patients.

BACKGROUND:Previous studies have demonstrated that icariin has important roles in promoting bone formation and inhibiting bone resorption,but its effects on osteoporosis-mediated bone pain have not been reported. OBJECTIVE:To investigate the possible mechanism of icariin alleviating bone pain in postmenopausal senile osteoporosis. METHODS:(1)Animal experiment:200 C57BL/6 mice were randomly divided into 4 groups:sham group(n=50),model group(n=50),icariin treatment group(n=50),and carbonic anhydrase Ⅱ inhibitor(Brinzolamide)treatment group(n=50).Ovariectomy was performed on C57BL/6 mice to establish a postmenopausal osteoporosis model in all groups except the sham group.The icariin group was given icariin on the second day after modeling,and pain behavior tests(Von Frey,Hot Plate,and Tail Flick tests)were performed every 2 weeks for 20 weeks.After sampling,bone mass was detected by microCT,osteoclast activity was detected by hematoxylin-eosin and tartrate-resistant acid phosphatase staining,and neuronal morphology and related ion channel expression were detected by tissue immunofluorescence staining.(2)Cell experiment:Osteoclast precursor cells derived from mouse bone marrow were extracted and induced to differentiate into osteoclasts using the RANKL/M-CSF system in vitro and supplemented with icariin of different concentrations(1 and 10 μmol/L).Tartrate-resistant acid phosphatase staining was used to detect osteoclast differentiation,ghost pen cyclic peptide staining was used to detect osteoclast actin ring,bone plate absorption assay was used to detect osteoclast osteophagy function,pH value of the system was detected by pH meter,and expression of osteoclast differentiation-related proteins was detected by western blot.In addition,mouse dorsal root ganglion-derived nerve cells were extracted and treated with icariin.Cell counting kit-8 was used to detect neuronal activity and CGRP staining was used to detect neuronal morphology. RESULTS AND CONCLUSION:Compared with the model group,the icariin treatment group had higher bone mineral density,fewer tartrate-resistant acid phosphatase-positive osteoclasts in bone tissue,decreased neuronal activity,and decreased neuronal transient receptor potential vanilloid subtype 1 channel and carbonic anhydrase Ⅱ expression.Behavioral results showed that the icariin treatment group was less sensitive to pain than the model group.Icariin inhibited osteoclast differentiation and bone phagocytosis in vitro.Icariin enhanced the activity of dorsal root ganglion neurons and inhibited the expression of calcitonin gene-related peptide and transient receptor potential vanilloid subtype 1 channels in dorsal root ganglia in a relatively non-toxic pH range.To conclude,icariin alleviates bone pain caused by postmenopausal osteoporosis by regulating the acidic microenvironment through its effect on osteoclasts.

Objective To explore the effects of exposure to lipopolysaccharides in late pregnancy on age-related cognitive changes in offspring of mice,and to investigate whether there is a gender specific genetic effect.Methods Institute of cancer research(ICR)CD-1 mice during gestational days 15-17 were injected with lipopolysaccha-ride daily(LPS group,50 μg/kg),or equal volume of normal saline(CON group).At the age of 2 months after their delivery,LPS treated offspring mice(F1-LPS,male and female)were randomly selected and hybridized with age-matched wild-type CD-1 mice.F1-LPS males and females with different littermates,and F1-CON males and fe-males were hybridized to obtain F2 generations of different lineages.Similarly,F2-LPS mice were mated with wild-type mice to conceive the F3 generation.At the age of 3 and 18 months old,F1,F2,and F3 mice(n=8 in each group)were randomly selected to complete the Morris maze experiment in order to test their cognitive abilities.Re-sults Compared with 3-month-old CON mice,18-month-old CON mice showed poorer learning and memory abili-ties,especially in females.For Fl generation,the learning and memory abilities of the 3-month-old and 18-month-old F1-LPS mice were inferior to those of the same aged CON mice.For F2 generation,the 3-month-old F2-LPS-parental mice had poorer learning and memory compared to the same aged CON mice,while the F2-LPS-paternal mice only had poorer memory compared to the same aged CON group.The learning and memory abilities of 18-month-old F2-LPS paternal and F2-LPS-parental mice were inferior to those of the same aged CON mice.The learn-ing and memory abilities of F2-LPS maternal male mice were inferior to those of CON male mice,and the memory abilities of F2-LPS maternal mice were stronger than those of F2-LPS-parental mice.With regards to the F3 genera-tion,the memory of the 3-month-old F3-LPS-parental mice was poorer than that of the same aged CON mice.The learning and memory abilities of F3-LPS paternal and F3-LPS-parental mice at 18 months old were inferior to those of CON mice of the same age.The 18-month-old F3-LPS maternal and paternal male mice had better memory than F3-LPS-parental male mice.Conclusion Exposure to lipopolysaccharides in late pregnancy can accelerate age-re-lated cognitive decline in offspring mice,and it has a cross generational genetic effect and gender differences,mainly in paternal inheritance.

OBJECTIVE To establish fingerprints and multi-components determination of Jieze lotion, and use chemometrics methods for quality evaluation. METHODS The HPLC-DAD fingerprints was established and 10 components were recognized by comparison with references. Meanwhile, their contents were determined. The data were evaluated by the methods of chemometrics such as similarity evaluation, cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis. RESULTS The similarity of 11 batches of Jieze lotion were all >0.95. The linearity was good(r≥0. 999 1) and the average recoveries were between 89.70% and 106.0% with the RSD of 1.52%−3.41%. Instrument precision, stability and reproducibility of the method were all great. The contents of the common ten components(gallic acid, protocatechuic acid, neochlorogenic acid, caftaricacid, 5-O-feruloylquinicacid, chlorogenic acid, phellodendrine chloride, magnoflorine, 4-O-feruloylquinic acid, berberinehydrochloride) were 40.103−55.841, 2.347−6.179, 8.336−23.810, 7.084−21.956, 33.098−53.833, 24.597−49.610, 21.587−31.188, 5.915−13.162, 115.381−189.702, 31.378−112.686 μg·mL−1, respectively. The results of chemometrics showed that the 11 batches of samples could be divided into 4 categories, and the strong characteristic peaks used to distinguish each batch of samples were berberine hydrochloride, 4-O-feruloylquinic acid, chlorogenic acid, neochlorogenic acid and 5-O-feruloylquinic acid. CONCLUSION The method is accurate and reliable, and it can be used for the quality control and comprehensive evaluation of Jieze lotion.

Objective To investigate the correlation between red blood cell distribution width(RDW),systemic immune-inflammation index(SII)and major depressive disorder(MDD).Methods The clinical data of 176 MDD patients hospitalized in the clinical psychology department of our hospital from 2020 to 2022 and 209 non-MDD comparators who were routinely examined in Hebei General Hospital were retrospectively analyzed.Blood analysis was conducted to obtain values of RDW,SII,and red blood cell distribution width/platelet ratio(RPR).The data was used to plot the receiver operator characteristic(ROC)curve to determine the optimal threshold and the area under the curve(AUC)for RDW to discriminate between patients and controls.Result Patients in the MDD group had significantly higher RDW[median and quartiles:13.20(12.70,13.98)vs.12.80(12.40,13.35)],and SII levels[median and quartiles 510.87(350.95,878.12)vs.405.33(313.74,539.92)]compared with those in non-MDD group(P<0.05).There was no significant difference in RPR between the two groups(P>0.05).Multifactorial logistic regression analysis showed that RDW was positively correlated with MDD after adjusting for confounders(OR=3.086,95% CI:1.926-4.944).ROC curve showed that the optimal threshold for RDW to differentiate the risk of developing MDD was 12.85,with an AUC of 0.647(95% CI:0.592-0.702;P<0.001).Conclusion Present study shows that high RDW is a risk factor for the occurrence of MDD and an important parameter for the risk of developing depression.

Objective To investigate the risk factors for post-traumatic epilepsy(PTE)after traumatic brain injury(TBI).Methods According to PTE,169 patients with TBI were divided into PTE group and non-PTE group.Clinical data of the patients were collected and compared.Non-parametric test and binary Logistic regression were used to analyze the risk factors of PTE.Results Compared with those in non-PTE group,there were significant differences in psychiatric symptoms,GCS score,abnormal imaging examination type,injury type and post-traumatic seizures(PTS)ratio in the PTE group(P<0.05-0.01).Binary Logistic regression showed that GCS score,abnormal imaging examination type,psychiatric symptoms and PTS were independent risk factors for PTE(OR=5.825,95%CI:1.062-31.947,P=0.042;OR=6.942,95%CI:1.542-31.244,P=0.012;OR=31.059,95%CI:9.295-103.786,P<0.001;OR=0.099,95%CI:0.042-0.231,P<0.001).Conclusion GCS score,abnormal imaging examination type,psychiatric symptoms and PTS are independent risk factors PTE after TBI.

Objective:To establish an automated labeling method of 18F-AlF-1, 4, 7-triazocyclohexane-1, 4, 7-triacetic acid- D-Phe1-Tyr3-Thr8-octreotide (NOTATATE) and perform neuroendocrine tumor (NET) imaging. Methods:Based on the GE-FASTLab2 synthesis module, 18F-AlF-NOTATATE was automatically prepared by one-step chelation labeling with aluminum fluoride, and its labeling conditions were optimized. The product quality was analyzed. One patient (male, 47 years old) with lower rectal segment NET and one patient (female, 52 years old) with pancreatic NET underwent 18F-AlF-NOTATATE PET/CT imaging. Results:18F-AlF-NOTATATE was successfully prepared with a total synthesis time of 35 min. The optimized radiochemical yield was (23.8±3.1)% (without decay correction, n=3), the radioactivity was (4.63±0.68) GBq, and the radiochemical purity was >95%. The stability was good, and the product quality met the requirements. 18F-AlF-NOTATATE showed clear imaging in the patient with rectal segment NET, with SUV max of 13.3 and tumor/liver ratio of 3.3. Metastatic lesions in the liver, lymph nodes, and ribs showed high SUV max and tumor/liver ratios. The imaging of the pancreatic NET patient showed an abnormal increase in local radioactive uptake at the uncinate process of the pancreatic head, with SUV max of 5.6 and SUV max of 6.3 and the tumor/liver ratio of 2.3 after 2-hours imaging. Conclusions:Using the GE-FASTLab2 synthesis module, 18F-AlF-NOTATATE can be prepared with high activity. The preparation is simple, the method is stable, and the product has high radiochemical purity. 18F-AlF-NOTATATE exhibits good imaging performance in NET patients, providing valuable information for diagnosis, treatment, and prognosis evaluation.

Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S₂ (S₂) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S₂ for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S₂, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S₂ resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

Objective To investigate the HIV-1 genotype and distribution of newly diagnosed HIV-1 cases in Fujian Province in 2020, so as to provide insights into formulation of the precise AIDS control strategy in the province. Methods Newly diagnosed HIV-1 cases without antiretroviral therapy (excluding AIDS patients) were randomly sampled from each city of Fujian Province in 2020 at a proportion of 50% of the mean number of HIV-infected cases reported across 9 cities of Fujian Province during the past three years. Subjects’ demographic and epidemiological data were collected and blood samples were collected. The HIV-1 pol gene was amplified using nested reverse-transcription PCR assay, and the gene sequences were used for HIV-1 genotyping and phylogenetic analysis. The gene sequences were uploaded to the HIV Drug Resistance Database (http://hivdb.stanford.edu) for genotypic drug resistance assays, and the scores and level of HIV drug resistance were estimated using the HIVDB Algorithm version 9.5. Results A total of 1 043 newly diagnosed HIV-1 cases were reported in Fujian Province in 2020, and 936 gene sequences were successfully obtained following sequencing of blood samples. There were 9 HIV-1 genotypes characterized in blood samples from 936 newly diagnosed HIV-1 cases, with CRF07_BC (52.1%) and CRF01_AE (30.4%) as predominant subtypes, followed by CRF08_BC (4.9%), CRF55_01B (3.0%), subtype C (2.5%), subtype B (2.1%), CRF85_BC (1.7%), CRF59_01B (0.3%) and CRF65_CPX (0.1%), and unidentified subtypes were found in 26 blood samples. HIV-1 drug resistance was detected in 43 out of the 936 newly diagnosed HIV-1 cases, with 4.6% prevalence of HIV-1 drug resistance prior to therapy, and the highest drug resistance was found in the HIV CRF59_01B subtype, followed by in CRF08_BC, B, C, CRF01_AE, CRF07_BC and other subtypes, with a significant difference in the genotype-specific prevalence of HIV-1 drug resistance (χ² = 45.002, P < 0.05). Conclusions There was a HIV-1 genotype diversity in Fujian Province in 2020, and emerging recombinant and drug-resistant HIV-1 strains were detected and spread across patients and regions. Monitoring of HIV-1 genotypes is recommended to be reinforced for timely understanding of the transmission and spread of novel recombinant and drug-resistant HIV-1 strains.