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.

ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

AIM: To investigate the correlation between the expression of serum lipocalin 2(LCN2), chemokine like receptor 1(CMKLR1), and C-C motif chemokine ligand 11(CCL11)and the severity of disease in patients with type 2 diabetes mellitus(T2DM)and dry eye(DE).METHODS:A prospective selection of 97 patients(194 eyes)diagnosed with T2DM and DE at our hospital from May 2022 to May 2024 was made as the DE group, which was further divided into mild(47 cases, 94 eyes), moderate(34 cases, 68 eyes), and severe(16 cases, 32 eyes)subgroups based on the severity of dry eye. Additionally, 97 patients(194 eyes)of T2DM without DE were selected as non-DE group, and 97 healthy volunteers(194 eyes)who underwent physical examination during the same period were chosen as control group. Serum levels of LCN2, CMKLR1, and CCL11 were measured in all participants. Spearman correlation analysis was used to assess the relationship between serum levels of LCN2, CMKLR1, and CCL11 and the severity of DE in T2DM patients; multivariate Logistic analysis was used to analyze the factors affecting the severity of T2DM patients with DE. The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of serum LCN2, CMKLR1 and CCL11 levels for moderate to severe dry eye in T2DM patients.RESULTS: Serum levels of LCN2, CMKLR1, and CCL11 increased progressively from the control group to the non-DE group and then to the DE group(all P<0.05). Within the DE group, these levels also increased progressively from the mild to moderate and then to the severe subgroups(all P<0.05). Spearman correlation analysis showed that serum levels of LCN2, CMKLR1, and CCL11 were positively correlated with the severity of disease(rs=0.604, 0.591, 0.559, respectively; all P<0.05). Stepwise forward multivariate Logistic analysis showed that Schirmer's test(SⅠt), tear break-up time(BUT), serum levels of LCN2, CMKLR1 and CCL11 were the factors affecting the severity of T2DM patients with DE; ROC curve analysis indicated that the combined diagnosis of serum LCN2, CMKLR1, and CCL11 for the progression of T2DM with DE to moderate-to-severe stages had an area under curve(AUC)value of 0.896, which was significantly higher than that of individual diagnoses of LCN2, CMKLR1, and CCL11(Z=2.925, 2.704, 3.483, respectively; P=0.003, 0.007, <0.001).CONCLUSION: Serum LCN2, CMKLR1 and CCL11 levels are increased in T2DM patients with DE, and are positively correlated with the severity of DE. The combination of the three has a high diagnostic value for moderate to severe DE.

As a new type of production factor that can empower the development of new quality productivity, the data element is an important engine to promote the high quality development of the industry. Traditional Chinese medicine(TCM) dispensing is the most basic work of TCM clinical pharmacy, and its quality directly affects the clinical efficacy of TCM. The integration of data elements and TCM dispensing can stimulate the innovation and vitality of the TCM dispensing industry and promote the high-quality and sustainable development of the industry. A large-scale, detailed, and systematic study on TCM dispensing was conducted. The innovative practice path of data fusion construction in the whole process of TCM dispensing was investigated by integrating the digital resources "nine full activities" of TCM dispensing, creating the digital dictionary of "TCM clinical information data elements", and exploring innovative applications of TCM dispensing driven by data and technology, so as to promote the standardized, digital, and intelligent development of TCM dispensing in medical health services. The research content of this project was successfully selected as the second batch of "Data element×" typical cases of National Data Administration in 2024, which is the only selected case in the field of TCM.
Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal ; Humans

OBJECTIVE: Meta-analysis of the clinical efficacy of plate and external fixator fixation in the treatment of AO-C type distal radius fractures. METHODS: PubMed, Embase, Cochrane Medical Library, Web of Science, CNKI, Wanfang, VIP and SinoMed databases were searched for all literature on randomized controlled clinical trials of AO-C distal radius fractures. The search time limits were from each database. The database will be established until June 30, 2023. The included studies were extracted according to the Cochrane Handbook (Version 6.3, 2022) for information extraction and literature quality evaluation. RevMan 5.4 was used to evaluate the risk of Publication bias, test heterogeneity and Perform Meta-analysis. The outcome indicators were:imaging anatomy indicators (volar inclination angle, ulnar deviation angle, radial height), wrist joint mobility (flexion, extension, rotation, ulnar deviation), complication rate, and comparison of surgical treatments (operative blood loss, operation time, hospitalization time, fracture healing time) and wrist joint function scores and related scales. RESULTS: (1) A total of 28 studies were included, with a total of 2 192 patients, including 1 096 cases in the plate internal fixation group and 1 096 cases in the external fixation group.(2) Meta analysis results showed:the surgical treatment situation of the external fixation group:surgical blood loss MD=-37.93, 95%CI(-48.54, -27.31), P<0.000 01;operation time MD=-31.58, 95%CI(-48.96, -14.20), P<0.000 4;hospitalization time MD=-4.58, 95%CI(-5.44, -3.71), P<0.000 01;the fracture healing time MD=-0.88, 95%CI(-1.35, -0.41), P<0.000 2, which were significantly better than that of the plate internal fixation group(P<0.05).(3) The two groups:palmar inclination angle MD=-0.17, 95%CI(-0.95, 0.61), P=0.68;ulnar declination MD=0.22, 95%CI(-0.73, 1.17), P=0.65, radial height MD=-0.24, 95%CI(-1.15, 0.67), P=0.60;flexion and extension MD=-5.63, 95%CI(-11.85, 0.58), P=0.08;rotation MD=-5.80, 95%CI(-12.77, 1.17), P=0.10, radioulnar deviation MD=-2.86, 95%CI(-10.87, 5.15), P=0.48;complication rate RR=0.96, 95%CI(0.63, 1.46), P=0.83;Gartland-Werley clinical wrist score MD=0.13, 95%CI(-0.80, 1.06), P=0.78;excellent and good rate of Gartland-Werley wrist clinical score RR=0.93, 95%CI(0.87, 1.01), P=0.08;excellent and good rate of Cooney wrist score RR=0.99, 95%CI(0.62, 1.59), P=0.98;wrist DASH score MD=-4.67, 95%CI(-14.96, 5.62), P=0.37;the differences were not significant (P>0.05). CONCLUSION Compared with internal fixation with plate, external fixation can significantly reduce the amount of surgical bleeding, shorten the operation time, hospitalization time and fracture healing time, and its imaging anatomical indicators, wrist mobility, and complications can be significantly reduced in treating AO-C distal radius fractures. Rates and wrist function scores were equivalent.
Humans ; External Fixators ; Bone Plates ; Radius Fractures/surgery* ; Fracture Fixation/methods* ; Fracture Fixation, Internal ; Wrist Fractures

Objective To investigate the impact of Qizhi Jiangtang Capsule (QZJT) on renal damage in diabetic nephropathy (DN) mice via NOD like receptors family pyrin domain containing 3/caspase-1/ Gasdermin D (NLRP3/caspase-1/GSDMD) signaling pathway. Methods Mice were randomly allocated into six experimental groups: a normal control group (NC), a diabetic nephropathy model group (DN), a low-dose QZJT treatment group (L-QZJT), a high-dose QZJT treatment group (H-QZJT), a positive control group administered Shenqi Jiangtang Granules (SQJT), and an ML385 group (treated with an inhibitor of nuclear factor erythroid 2-related factor 2, Nrf2). Upon successful model induction, therapeutic interventions were commenced. Renal function impairment in the mice was evaluated through quantification of fasting blood glucose (FBG), 24-hour urinary albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and the kidney-to-body mass ratio (K/B). Renal tissue pathology was evaluated using HE and PAS staining. Serum levels of inflammatory cytokines IL-1β and IL-18 were quantified by ELISA. Levels of podocyte markers and proteins involved in relevant pathways were assessed using Western blot analysis. Results Compared with the NC group, FBG, 24 h UAlb, SCr, and BUN were increased in the DN group, and the K/B mass ratio was also increased. In contrast, compared with the DN group, FBG, 24 h UAlb, SCr, and BUN in both the low-dose (L-QZJT) and high-dose Quanzhou Jintang (H-QZJT) groups were decreased, and the K/B mass ratio was decreased as well. The therapeutic efficacy of H-QZJT was comparable to that of Shenqi Jiangtang Granules. QZJT ameliorated renal histopathological injury in DN mouse, increased the protein levels of Nephrin (a podocyte marker), and decreased the protein levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), pro-caspase-1, and GSDMD-N. After ML385 treatment, renal cells exhibited swelling and morphological changes, the inflammatory infiltrate area was enlarged, the protein levels of NLRP3, ASC, pro-caspase-1, and GSDMD-N were up-regulated, and the levels of IL-1β and IL-18 were increased. Conclusion QZJT may inhibit podocyte pyroptosis by acting on the Nrf2 to regulate the NLRP3/caspase-1/GSDMD pathway, thus improving renal damage in DN mouse.
Animals ; Diabetic Nephropathies/pathology* ; Podocytes/pathology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Pyroptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 1/genetics* ; Signal Transduction/drug effects* ; Mice ; Phosphate-Binding Proteins/genetics* ; Male ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Kidney/pathology* ; Gasdermins

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

OBJECTIVE: To explore the influencing factors on the prognosis of patients with multiple myeloma (MM) after bortezomib treatment, and construct a decision tree risk prediction model based on the influencing factors. METHODS: One hundred and seventy MM patients admitted to the People's Hospital of Jianyang City from January 2019 to June 2022 were selected as research subjects, and divided into poor prognosis group and good prognosis group according to the prognosis after bortezomib treatment. The clinical data of the patients were analyzed, univariate and logistic regression analysis were used to screen influencing factors, SPSS Modeler software was used to construct a decision tree prediction model, and the diagnostic performance of the decision tree risk prediction model was analyzed. RESULTS: The incidence of poor prognosis in 170 MM patients after bortezomib-based chemotherapy was 21.18%. Kappa light chain level≥19.4 mg/L, platelet count (PLT) ≤100×10⁹/L, homocysteine (Hcy) >22 μmol/L, serum creatinine (Scr) ≥176 μmol/L, lactate dehydrogenase (LDH) ≥300 U/L, serum ferritin (SF) >500 mg/L, and β₂-microglobulin (MG) >6 μg/L were independent risk factors for poor prognosis in MM patients after bortezomib treatment (all P < 0.05). The decision tree model selected 7 explanatory variables (Kappa light chain level, LDH, PLT, SF, β₂-MG, Scr, and Hcy) as nodes of the model, among which Kappa light chain level was the most important predictor. In addition, the area under the ROC curve (AUC) values of the decision tree model and logistic regression model were 0.895 and 0.881, respectively. The prediction performance of the decision tree model was better than that of the logistic regression model ( Z=3.325, P =0.005). CONCLUSION The decision tree model has high value in predicting the prognosis after bortezomib treatment in MM patients, which can screen high-risk factors that affect poor prognosis, providing practical references for clinical healthcare professionals to take preventive treatment for high-risk MM patients.
Humans ; Bortezomib/therapeutic use* ; Multiple Myeloma/diagnosis* ; Decision Trees ; Prognosis ; Algorithms ; Risk Factors ; Male ; Female ; Middle Aged

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome