ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

BACKGROUND:With the development of computer-aided design and computer-aided manufacturing technology,zirconia abutments with a titanium base are widely used in clinic due to its good application advantages,but there are still some problems and a lack of consensus design standards. OBJECTIVE:To review the fabrication methods of Ti-base zirconia abutment,and the effect of abutment connection,emergence design,abutment angle,and bonding on mechanical properties of Ti-base zirconia abutment. METHODS:Relevant literature published from 2010 to 2023 was searched in CNKI and PubMed databases with the search terms"zirconia abutment,titanium base"in Chinese and English,respectively.The search time limit was extended for some classical literature.The relevant literature was obtained through inclusion and exclusion criteria,and 57 eligible documents were included for review. RESULTS AND CONCLUSION:It is recommended that clinicians try to select antirotational titanium bases or rotational titanium bases with a Morse taper connection.Implants should be placed in the correct axial angulation of not more than 15° or with an inclination to the palatal side when using angled zirconia abutments.When a≥30° labial inclination is followed for implant placement,the bite force must be decreased effectively to reduce the risk of mechanical and biological complications of implants,abutments,and prostheses.Ti-base zirconia abutments with a higher gingival height should be selected,and its restorative angle should not exceed 40°.Multilink Hybrid Abutment could be the first choice for extraoral bonding of zirconia abutment to titanium bases.

BACKGROUND:Unlike non-inflammatory cell apoptosis,pyroptosis is a form of inflammatory cell death,characterized by membrane integrity disruption and release of pro-inflammatory intracellular substances.Thus,it is associated with various diseases.The sirtuin family is a group of histone deacetylases dependent on nicotinamide adenine dinucleotide.In addition to deacetylation,it also possesses other enzymatic activities such as desuccinylation,demalonylation,adenosine diphosphate-ribosylation and playing crucial roles in the regulation of pyroptosis.OBJECTIVE:To review the role of the sirtuins in pyroptosis.METHODS:The first author conducted a search on PubMed,Web of Science,CNKI,and WanFang Data from inception to March 2024,using the Chinese and English search terms"Sirtuins,Sirtuin1,Sirtuin2,Sirtuin3,Sirtuin4,Sirtuin5,Sirtuin6,Sirtuin7,pyroptosis",resulting in the inclusion of 71 articles.RESULTS AND CONCLUSION:(1)The sirtuin family all participates in the regulation of pyroptosis.(2)Overexpression of sirtuin1 and sirtuin4 can inhibit pyroptosis through various pathways,thus alleviating the damage caused by pyroptosis to the organism.(3)In addition to affecting the classical pathway of pyroptosis,sirtuin3 can also inhibit pyroptosis by enhancing mitochondrial reactive oxygen species scavenging capacity and mitosis.(4)Sirtuin5 is involved in the regulation of intracellular metabolism and energy balance,including energy intake,storage,and consumption.(5)Sirtuin6 can influence pyroptosis through various pathways and also affect macrophage M1 polarization,generation of reactive oxygen species,and cleavage of pyroptosis-related factor sclerotin D to inhibit pyroptosis.(6)Overexpression of sirtuin7 can suppress pyroptosis.(7)Sirtuin2,unlike other family members,can restrain pyroptosis only after knockdown,but there are fewer reports,requiring more in-depth and comprehensive research.

Objective To observe the effects of 3 different nutritional support modes of nasogastric tube nutrition,nasoenteric tube nutrition and nasoenteric tube combined with nasogastric tube nutrition on the biliary-related indices of critically ill patients.Methods The observational research method was conducted,the patients admitted to the department of intensive care unit(ICU)of Qingdao Hospital,University of Health and Rehabilitation Sciences(Qingdao Municipal Hospital)from June 2023 to May 2024 serving as the subjects of the study.The subjects were divided into three groups,namely the nasogastric tube group(indwelling nasogastric tube for enteral nutrition),the nasoenteric tube group(indwelling nasoenteric tube for enteral nutrition),and the mixed nutrition group(indwelling nasoenteric tube combined with naso-gastric tube for enteral nutrition)according to the different modes of enteral nutrition given.The clinical data of the patients was collected,including gender,age,previous underlying diseases,nutritional risk screening 2002(NRS2002)score,acute physiology and chronic health evaluationⅡ(APACHEⅡ),gallbladder volume,data on laboratory-related indices,and prognosis during hospitalisation.Compare the differences between the observed indicators and their change values before and after the initiation of enteral nutrition within each group;analyse the correlation between gallbladder volume and other observed indicators using Spearman's correlation analysis;screen the influencing factors of gallbladder volume using univariate regression analysis;screen the influencing factors of ICU patients'survival during hospitalisation using multifactorial Logistic regression analysis,and plot the receiver operator characteristic curve(ROC curve)of the subjects to analyse the predictive value of each influencing factor on patients'prognosis.Results A total of 141 patients who met the inclusion criteria were included in the study,comprising 54 cases in the nasogastric tube group,38 cases in the nasoenteric tube group,and 49 cases in the mixed nutrition group.Of the patients who survived during ICU hospitalization,105 survived,while 36 died,mortality was 25.53%.① No statistically significant differences were observed in the comparison of gender,age,previous underlying disease,NRS2002 score,and APACHEⅡscore among the enrolled groups.② A comparative analysis was conducted on the biliary-related indexes of the nasogastric tube and nasoenteric tube groups before and after the initiation of enteral nutrition.The results revealed no statistically significant differences between the two groups.On the 7th day of enteral nutrition initiation,the gallbladder volume of the nasoenteric tube group was found to be significantly larger than the gallbladder volume on the 1st day(cm3:28.00±6.36 vs.25.20±4.75,P<0.05).In the mixed nutrition group,the gallbladder volume on the initiation of enteral nutrition on day 7 was significantly smaller than that on the 1st day of initiating enteral nutrition(cm3:25.03±4.69 vs.28.68±5.96,P<0.05).③A comparative analysis was conducted among the three groups,revealing significant variations in the values of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),indirect bilirubin(IBil),alkaline phosphatase(ALP),γ-glutamyltranspeptidase(γ-GT),and gallbladder volume across the groups.From 1-7 days following the initiation of enteral nutrition,the bile-related indexes in the nasoenteric tube group exhibited an increasing trend,while the bile-related indexes in the mixed nutrition group demonstrated a decreasing trend.④ Spearman correlation analysis showed that gallbladder volume was significantly and positively correlated with AST,ALT,ALP,and γ-GT(r values of 0.398,0.299,0.242,and 0.262,respectively,all P<0.01).⑤ Multivariate Logistic regression analysis demonstrated that the initiation of enteral nutrition for 7 days was associated with a significant advantage,as indicated by an odds ratio(OR)of 1.031,with a 95%confidence interval(95%CI)of 1.004-1.058,and a P value was 0.024.Furthermore,the initiation of enteral nutrition for 7 d AST(OR=1.031,95%CI was 1.004-1.058,P=0.024),TBil(OR=1.187,95%CI was 1.039-1.355,P=0.011),and IBil(OR=0.707,95%CI was 0.542-0.921,P=0.010),and γ-GT(OR=0.985,95%CI was 0.972-0.999,P=0.034)were all factors affecting the survival of ICU patients during hospitalisation.Conclusions In the context of patients receiving intensive care,the prolonged utilisation of nasoenteric feeding tubes for a duration exceeding seven days has been observed to potentially induce an augmentation in gallbladder volume and an elevation in biliary-related indices,including ALT,AST,ALP,and γ-GT.The concomitant administration of nasogastric feeding,grounded in the foundation of simple nasoenteric tube nutrition,has been demonstrated to result in a reduction of these biliary-related indices to a certain extent.

Chronic hepatitis B (CHB) can gradually progress to life-threatening diseases such as cirrhosis and hepatocellular carcinoma (HCC). In recent years, with the change in people's lifestyles, the incidence rate of metabolic associated fatty liver disease has been steadily increasing and the patients combined with CHB and MAFLD has significantly surged. However, the impact of MAFLD on patients with CHB in aspects of antiviral response, clinical outcomes, and others is still controversial. This article reviews research progress on the impact of MAFLD with regard to natural course and antiviral treatment response in CHB and the survival rate in combination with CHB and MAFLD so as to provide a certain theoretical reference for prevention, diagnosis, and treatment of this disease.

AIM To evaluate the chemical constituent consistency in formula granules and traditional decoctions of Gouteng Jiangya Formula.METHODS HPLC characteristic chromatograms were established,the analysis was performed on a 30 ℃ thermostatic YMC-Triart C18 column(4.6 mm× 250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2％phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.Puerarin was used as an internal standard to calculate the relative correction factors of 3'-methoxy puerarin,puerarin apioside,magnolflorine,paeoniflora,daidzin,baicalin,palmatine,berberine,wogonoside and benzoylpaeoniflorin,after which the content detemination was made by quantitative analysis of multi-components by single-marker(QAMS).RESULTS The characteristic chromatograms of 9 batches of formula granules and 15 bacthes of traditional decoctions demonstrated the similarities of more than 0.90 at the detection wavelengths of 192,210,240,260,280,300,320,360 nm,along with similar total peak areas.Eleven constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 97.27％-101.64％with the RSDs of 0.36％-1.11％,the result obtained by QAMS and external standard method demonstrated no significant differences(P＞0.05).The contents of various constituents in the formula granules approximated those in the traditional decoctions.CONCLUSION The consistent kinds and contents of various constituents are obversable in formula granules and traditional decoctions of Gouteng Jiangya Formula,which can provide a reference for the reasonable clinical application of this formula.

Objective:To compare the efficacy of cannulated screw internal fixation combined with quadratus femoris bone flap with preservation of the posterior superior retinaculum and cannulated screw internal fixation alone in the treatment of femoral neck fracture in young and middle-aged patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 83 young and middle-aged patients with femoral neck fracture admitted to the 920th Hospital of Joint Logistic Support Force of PLA from January 2018 to January 2023, including 56 males and 27 females, aged 28-55 years [(42.7±3.2)years]. According to Garden classification, the fractures were classified as type III in 22 patients and type IV in 61. Based on Pauwels classification, the fractures were classified as type I in 15 patients, type II in 38 and type III in 30. Forty patients were treated with cannulated screw internal fixation combined with modified quadratus femoris bone flap (cannulated screw combined with bone flap group) and 43 with cannulated screw internal fixation alone (cannulated screw group). The two groups were compared in terms of the operation time, intraoperative blood loss, time to weight-bearing, length of hospital stay, and wound healing. The visual analogue scale (VAS) scores and Harris hip function scores at 1, 3, 6, 12 months after surgery and at the last follow-up. The postoperative complication rate was detected.Results:All the patients were followed up for 20-70 months [(40.0±1.2)months]. The operation time and intraoperative blood loss were (105.2±2.7)minutes and (100.6±16.3)ml in the cannulated screw combined with bone flap group, which were longer or more than (92.4±4.7)minutes and (92.5±14.6)ml in the cannulated screw group ( P<0.01). The time to weight-bearing was (12.1±1.4)weeks in the cannulated screw combined with bone flap group, shorter than (23.6±1.2)weeks in the cannulated screw group ( P<0.01). There was no statistically significant difference in the length of hospital stay between the two groups (P>0.05). The incisions in both groups were healed by first intention. At 1 month after surgery, no statistically significant difference was observed in VAS scores between the two groups ( P>0.05); at 3, 6, 12 months after surgery and at the last follow-up, the VAS scores were (6.6±0.2)points, (4.5±0.3)points, (3.2±0.5)points, and (2.6±0.4)points in the cannulated screw combined with bone flap group, lower than (7.0±0.1)points, (5.2±0.2)points, (3.9±0.4)points, and (3.3±0.1)points in the cannulated screw group ( P<0.05 or 0.01). At 1 and 3 months after surgery, no statistically significant difference was observed in the Harris hip function scores between the two groups ( P>0.05); at 6, 12 months after surgery and at the last follow-up, the Harris hip function scores were (82.2±1.7)points, (90.0±1.4)points, and (91.6±1.0)points in the cannulated screw combined with bone flap group, higher than (75.2±1.7)points, (83.4±1.9)points, and (85.2±0.7)points in the cannulated screw group ( P<0.01). At the last follow-up, in the cannulated screw combined with bone flap group, the Harris hip function was rated excellent in 32 patients, good in 5, and fair in 3, with an excellent and good rate of 92.5%, while in the cannulated screw group, the Harris hip function was rated excellent in 20 patients, good in 13, and fair in 10, with an excellent and good rate of 76.7% ( P<0.05). The postoperative complication rate was 5.0% (2/40) in the cannulated screw combined with bone flap group, significantly lower than 23.2% (10/43) in the cannulated screw group ( P<0.05). Conclusion:Compared with cannulated screw internal fixation alone, cannulated screw internal fixation combined with quadratus femoris bone flap with preservation of the posterior superior retinaculum has the advantages of earlier weight-bearing, less pain, better recovery of hip joint function, and lower incidence of postoperative complications in the treatment of femoral neck fracture in young and middle-aged patients, despite longer operation time and more intraoperative blood loss.

Objective:To evaluate the safety and efficacy of donor-purified CD34 + stem cell boosts in patients with poor hematopoietic reconstruction (PHR) after haploid hematopoietic stem cell transplantation (haplo-HSCT) for aplastic anemia (AA) . Method:A retrospective analysis was conducted on 11 patients with AA and PHR who underwent haplo-HSCT and received donor-purified CD34 + stem cell boosts at Peking University People’s Hospital. Recovery of blood cell counts, incidence of graft-versus-host disease (GVHD), and overall survival (OS) were assessed. Results:Of the 11 patients with PHR, two were diagnosed with prolonged isolated thrombocytopenia (PT), one was primary poor graft function (PGF), and eight were diagnosed with secondary PGF. The median time to PHR diagnosis was 110 days (range: 60-330 days), and the median interval from transplantation to purified CD34 + hematopoietic stem cell infusion was 194 days (range: 125-456 days). The two patients with PT achieved complete platelet recovery at 22 and 13 days after CD34 + stem cell infusion, respectively. Among the remaining nine patients with PGF, six achieved complete hematopoietic recovery, with a median absolute neutrophil count recovery time of 19 days (8-158 days), HGB recovery time of 32.5 days (range: 13-158 days), and platelet recovery time of 31.5 days (range: 7-171 days). The incidence of chronic GVHD after infusion was 18.2%, with no cases of acute GVHD observed. The OS rate was 90.9% (10/11) in the 11 patients, with a median follow-up of 614 days (range: 153-1 765 days) . Conclusion:Donor-purified CD34 + stem cell boost may be an effective therapeutic strategy for PHR in patients with AA after haplo-HSCT.

OBJECTIVE: To detect the expression of methyltransferase-like 7B ( METTL7B) in bone marrow specimens of patients with acute myeloid leukemia (AML), and to analyze its influence and significance on clinical diagnosis, treatment, and prognosis of AML patients. METHODS: Bone marrow specimens from 60 newly diagnosed AML patients were collected as the observation group, and bone marrow specimens from 20 iron-deficiency anemia (IDA) patients were collected as the control group. Clinical and pathological data of AML patients were also collected. Real-time fluorescent quantitative PCR (qRT-PCR) was used to detect the expression of METTL7B in AML patients and IDA patients. Statistical analyses were performed to investigate the relationship between the expression level of METTL7B and clinical-pathological characteristics in AML patients, as well as the impact of METTL7B expression level on efficacy. Kaplan-Meier method was used to analyze the effect of METTL7B expression level on the overall survival time (OS) in AML patients. Meanwhile, a Cox proportional hazards regression model was constructed to identify the factors potentially affecting the prognosis of AML patients. RESULTS: Compared with the control group, the expression level of METTL7B was significantly upregulated in AML patients (P < 0.05). Compared with the low-expression group of METTL7B, the high-expression group had a higher proportion of patients with high white blood cell (WBC) count, poor prognosis, and ineffective treatment, and the differences were statistically significant (P < 0.05). The OS of patients in the high-expression group of METTL7B was significantly shorter than that in the low-expression group (P < 0.05). Multivariate Cox regression analysis showed that high WBC count, poor prognosis in prognosis stratification, and high expression of METTL7B were independent risk factors for the prognosis of AML patients (P < 0.05). CONCLUSION METTL7B is highly expressed in AML patients, and patients with high METTL7B expression exhibit shorter survival and poor prognosis. METTL7B is expected to serve as a new indicator for evaluating the prognosis of AML patients and may develop into a potential target for targeted treatment of AML in the future.
Humans ; Leukemia, Myeloid, Acute/metabolism* ; Prognosis ; Methyltransferases/metabolism* ; Male ; Female ; Middle Aged ; Adult ; Proportional Hazards Models