ObjectiveIdentification and analysis, animal regression test, and drug susceptibility study were conducted on a pathogenic strain causing diarrhea in cynomolgus monkeys, aiming to provide a practical basis for the clinical treatment of Citrobacter freundii. MethodsFresh fecal samples were collected from nine diarrheal cynomolgus monkeys and streaked on Salmonella-Shigella (SS) medium, LB medium, and Columbia blood agar medium, and incubated at 37 ℃ for 24 h. Subsequently, the isolated strain was identified by colony morphology observation, Gram staining, biochemical tests and 16S rRNA gene sequencing, and PCR was used to detect its major virulence genes. After propagation, the isolate was intragastrically administered to healthy cynomolgus monkeys and C57BL/6 mice for animal regression tests to evaluate its pathogenicity. Finally, the disk-diffusion method was used to detect the antimicrobial susceptibility of the isolate. ResultsA single bacterial strain, designated MF071743, was isolated from 9 fecal samples collected from diarrheal cynomolgus monkeys. The isolate formed pink, smooth, round colonies on SS medium; translucent, smooth, moist, shiny colonies with neat edges on LB medium; and smooth, moist, off-white colonies on Columbia blood agar medium. Gram staining revealed that the isolate was a Gram-negative, spore-free short bacillus. Biochemical tests showed that the isolate was positive for motility test, mannitol test, hydrogen sulfide test, methyl red test, citrate utilization test, gas production from glucose test, raffinose test, sorbitol test, and D-xylose test, but negative for phenylalanine test, gluconate test, indole test, Voges Proskauer (VP) test, urease test, lysine test, ornithine test, and adonitol test. The results of 16S rRNA gene sequencing showed that the gene sequence similarity between strain MF071743 and Citrobacter freundii was 99.0%. PCR results showed that this strain carries genes encoding the urease accessory proteins UreD, UreE, and UreF. Animal intragastric administration assays demonstrated that the strain caused loose stools in cynomolgus monkeys, and all C57BL/6 mice died within 72 h. Drug susceptibility test results indicated that the isolate was sensitive to 16 antibiotics, including ceftriaxone, amikacin, gentamicin, ceftazidime, and levofloxacin, while it exhibited resistance to 5 antibiotics, including ampicillin, cefazolin, vancomycin, erythromycin, and cephalexin. ConclusionA strain of Citrobacter freundii with certain drug resistance was isolated from the feces of diarrheal cynomolgus monkeys. The results of this study provide a reference for the diagnosis and treatment of gastrointestinal diseases in captive laboratory monkeys.

Alzheimer′s disease(AD), as a common cognitive impairment disorder in the elderly, has imposed a significant burden on the global public health system.The latest international diagnostic criteria emphasize defining AD from a biological perspective and viewing it as a continuous pathological and physiological change process.This article, guided by the principle of ′early diagnosis-precision intervention′, systematically elaborates on the current research status of AD regarding diagnostic criteria, biomarkers, new drug development, and the establishment of China-specific AD cohorts.It also provides an in-depth outlook on the future research directions and clinical application prospects of AD.

BACKGROUND:According to different locations of lumbar disc herniation,it can be classified into many types.Among them,patients with intradural sac type lumbar disc herniation have severe clinical symptoms,which greatly affect their quality of life.Therefore,this article studies the risk factors for its onset,and improving the preoperative diagnostic rate is of great significance for the treatment and prevention of this disease.OBJECTIVE:To explore the risk factors for intradural lumbar disc herniation.METHODS:A retrospective analysis was conducted on 15 patients with intradural lumbar disc herniation(herniation group)admitted to three hospitals in Xuzhou city from May 2014 to November 2022.Propensity score matching was used to match patients with lumbar disc herniation who did not protrude into the dura mater in a ratio of 1:4.A total of 59 patients were selected and included in the non-herniation group.Clinical data were observed in the two groups.Univariate and binary logistic regression analysis,multiple linear regression,and PROBIT regression analysis were utilized to identify the relevant risk factors for intradural lumbar disc herniation.RESULTS AND CONCLUSION:(1)The results of univariate analysis showed that the average disease course,proportion of segments,modified Pfiirmann grading,sacral tilt angle,proportion of previous lumbar spine surgery history,and proportion of heavy manual workers,proportion of lumbar spinal stenosis,redundancy of the cauda equina,and ossification of the posterior longitudinal ligament all showed statistical differences in the herniation and non-herniation groups(P＜0.05).(2)Multivariate regression analysis showed that duration of disease,protruding segment,history of lumbar surgery,modified Pfiirmann grading,cauda equina redundancy,and lumbar spinal stenosis were independent risk factors for intradural lumbar disc herniation.(3)Based on the influencing factors,an receiver operating characteristic curve was constructed,with an area under curve of 0.956(95％CI:0.913-0.998),indicating good discrimination.(4)There was a significant correlation between the duration of the disease,the protruded segment,the history of lumbar spine surgery,the modified Pfirmann classification,cauda equina redundancy,lumbar spinal canal stenosis,and the incidence rate of intradural lumbar disc herniation.

BACKGROUND:According to different locations of lumbar disc herniation,it can be classified into many types.Among them,patients with intradural sac type lumbar disc herniation have severe clinical symptoms,which greatly affect their quality of life.Therefore,this article studies the risk factors for its onset,and improving the preoperative diagnostic rate is of great significance for the treatment and prevention of this disease.OBJECTIVE:To explore the risk factors for intradural lumbar disc herniation.METHODS:A retrospective analysis was conducted on 15 patients with intradural lumbar disc herniation(herniation group)admitted to three hospitals in Xuzhou city from May 2014 to November 2022.Propensity score matching was used to match patients with lumbar disc herniation who did not protrude into the dura mater in a ratio of 1:4.A total of 59 patients were selected and included in the non-herniation group.Clinical data were observed in the two groups.Univariate and binary logistic regression analysis,multiple linear regression,and PROBIT regression analysis were utilized to identify the relevant risk factors for intradural lumbar disc herniation.RESULTS AND CONCLUSION:(1)The results of univariate analysis showed that the average disease course,proportion of segments,modified Pfiirmann grading,sacral tilt angle,proportion of previous lumbar spine surgery history,and proportion of heavy manual workers,proportion of lumbar spinal stenosis,redundancy of the cauda equina,and ossification of the posterior longitudinal ligament all showed statistical differences in the herniation and non-herniation groups(P＜0.05).(2)Multivariate regression analysis showed that duration of disease,protruding segment,history of lumbar surgery,modified Pfiirmann grading,cauda equina redundancy,and lumbar spinal stenosis were independent risk factors for intradural lumbar disc herniation.(3)Based on the influencing factors,an receiver operating characteristic curve was constructed,with an area under curve of 0.956(95％CI:0.913-0.998),indicating good discrimination.(4)There was a significant correlation between the duration of the disease,the protruded segment,the history of lumbar spine surgery,the modified Pfirmann classification,cauda equina redundancy,lumbar spinal canal stenosis,and the incidence rate of intradural lumbar disc herniation.

Alzheimer′s disease(AD), as a common cognitive impairment disorder in the elderly, has imposed a significant burden on the global public health system.The latest international diagnostic criteria emphasize defining AD from a biological perspective and viewing it as a continuous pathological and physiological change process.This article, guided by the principle of ′early diagnosis-precision intervention′, systematically elaborates on the current research status of AD regarding diagnostic criteria, biomarkers, new drug development, and the establishment of China-specific AD cohorts.It also provides an in-depth outlook on the future research directions and clinical application prospects of AD.

Objective To compare the accuracy of bedside lung ultrasound in emergency(BLUE)and combined cardiac-lung and additional ultrasound(CLAUS)for diagnosing the causes of acute dyspnea.Methods Totally 1 016 patients with acute dyspnea were retrospectively enrolled and divided into cardiogenic pulmonary edema group(n=268),pneumonia group(n=574),pneumothorax group(n=33),pulmonary embolism group(n=67)and CAD(chronic obstructive pulmonary disease/asthma/diaphragmatic dysfunction)group(n=74)according to the causes of acute dyspnea.The findings of CLAUS protocol were compared among groups,and the accuracy of BLUE and CLAUS protocol for diagnosing the causes of acute dyspnea were also compared.Results CLAUS showed that B-B and B-C were the most common modes in cardiogenic pulmonary edema group,while A-B/A-C/B-A/B-B/B-C/C-C modes were common in pneumonia group,and A-A mode was the most common in pneumothorax group,pulmonary embolism group and CAD group.Significant differences of the manifestations of pulmonary ultrasound,pleural feature of anterior chest wall,left/right cardiac insufficiency and abnormal inferior vena cava diameter were found among groups(all P＜0.05).The accuracy of BLUE and CLAUS protocol for diagnosing the causes of acute dyspnea was 86.91%(883/1 016)and 94.49%(960/1 016),respectively,the latter was higher than the former(χ2=34.587,P＜0.05).Conclusion CLAUS protocol could be used to effectively diagnose the causes of acute dyspnea,with higher accuracy than BLUE protocol.

Objective To investigate the role of cathepsin B(CTSB)inhuman cervical cancer HeLa cellswith Brucella infections.Methods The ctsb knockout(KO)HeLa cell line was constructed using CRISPR/Cas9.The effects of ctsbKO on cell proliferation and survival of intracellular bacteria in case of Brucella infection were detected by CCK-8 assay and intracellular bacteria count while the molecular mechanism of ctsb regulation on Brucella infection was revealed by Western blotting.Results The ctsbKO cell line was constructed.CCK-8 results showed that KO of ctsb had no impact on cell proliferationwith or without Brucella infection.The results of intracellular bacteria count showed a significant decrease in intracellular Brucella four days after infection in the KO cell line.Western blotting assay suggested that the expression levels of autophagy-related proteins were significantly down-regulated in the KO cell line with long-term Brucella infection.Conclusion KO of ctsb inhibits the intracellular survival of Brucella in long-term infections,providing a potential target for the treatment of chronic brucellosis.

Sepsis is a host reaction disorder caused by infection, in which oxidative stress is involved in the mechanism of organ damage. Vitamin C deficiency caused by trauma and infection is very common in critically ill patients. As a highly effective antioxidant, vitamin C can alleviate oxidative stress, reduce the inflammatory response, protect endothelial cell function, and reduce platelet activation. However, no definite clinical study confirms that patients with sepsis can benefit significantly from vitamin C supplementation. In order to further explore the clinical value of vitamin C in patients with sepsis, this paper discusses the pathophysiology of sepsis, the physiological function and deficiency of vitamin C, the basic research and clinical trials of vitamin C.

Objective:To analyze the cardio-pulmonary ultrasound features of cardiogenic pulmonary edema (CPE) and pneumonia in adults with acute dyspnea, and to construct a differential diagnosis model.Methods:Seven hundred and forty-three patients with sudden acute dyspnea admitted to Hebei General Hospital from November 2018 to May 2022 were retropectively included. Ultrasonographer A performed lung ultrasound with 12 zone method, and interpreted and recorded the ultrasonic signs (including A-lines area, B-lines area, consolidation area and pleural effusion area) together with ultrasonographer B. According to the ultrasonic characteristics of the whole lung, it was divided into A-profile and B-profile. According to the continuity and symmetry of the distribution of B-lines in bilateral lung fields, it could be divided into bilateral lung continuous and discontinuous B-profile, bilateral lung symmetric and asymmetric B-profile. Left ventricular ejection fraction (LVEF), left ventricular filling pressure (E/e′), right ventricular dilatation, tricuspid annular systolic displacement (TAPSE) and inferior vena cava diameter (IVCD) were evaluated by echocardiography, and all the indexes were transformed into binary variables. According to the final clinical diagnosis and treatment results, the disease was divided into CPE group and pneumonia group. Binary Logistic regression model was used to screen independent influencing factors, and partial regression coefficient β value was used as a weight to assign a score, and a differential diagnosis model was established based on the total score. The predictive value of the model was evaluated by the receiver operating characteristic curve (ROC) and area under curve (AUC). After the model was built, 30 patients with CPE or pneumonia were independently collected by ultrasonographer C as external validation data, which were included in the model to draw ROC curve and evaluate the differential diagnosis efficiency of the model. The consistencies between ultrasonographer A and B, A and C in observing lung ultrasound were explored.Results:A total of 743 patients from 43 clinical departments were included, including 246 cases in CPE group and 497 cases in pneumonia group. Multivariate logistic regression analysis showed that bilateral lung continuous B-profile, bilateral lung symmetric B-profile, ≥1 pleural effusion area, LVEF<50%, E/e′>14 were the risk factors for CPE (all OR>1, P<0.05), and ≥1 consolidation area and ≥1 pleural sliding disappearance area were the protective factors for CPE (all OR>1, P<0.05). The sensitivity, specificity and AUC of combined cardio-pulmonary ultrasound index β value weight score in the differential diagnosis of CPE and pneumonia were 0.939, 0.956 and 0.986, respectively. The AUC of external validation data was 0.904. Ultrasonographer A and B, A and C had good consistency in the interpretation of lung ultrasound signs ( P<0.05). Conclusions:The differential diagnosis model based on combined cardio-pulmonary ultrasound indexes has high differential diagnosis efficiency for CPE and pneumonia, and can be used in bedside cardio-pulmonary ultrasound practice.

Objective:To compare the changes of marginal bone resportion between immediate implantation and delayed implantation after 12 to 24 months of definitive prostheses finished.Methods:41 patients were recruited and divided into immediate implant placement group(n =20) and delayed implant placement group(n =21).All implants were evaluated via radiograph after surgery,6 months after implantion,1 year and 2 years after prostheses placement respectively,the height of marginal bone was measured 6 month after implation,1 year and 2 years after prostheses placement.Results:After 6 month,1 year and 2 year the mesial marginal bone attachement (MBA) of immediate implant placement group increased by (1.35 ± 1.12),(2.16 ± 1.73) and (2.53 ± 1.65) mm,the distal by (1.46 ± 1.17),(1.94 ± 1.16) and (2.32 ± 1.68) mm,respectively (among the 3 time points of examination,P ＜ 0.05).As for the delayed implantation group,in the mesial area MBA increased by (-0.52 ± 0.47),(-0.69 ± 0.58) and (-0.97 ± 0.78) mm,in the distal area by (-0.46 ± 0.44),(-0.60 ± 0.45) and (-0.72 ± 0.63) mm (among 3 time points,P ＞ 0.05).Conclusion:Immediate implantation is superior to delayed implantation for marginal bone attachement of dental implant.