This study aims to investigate the therapeutic effect and mechanism of Daotan Xixin Decoction on APP/PS1 mice. Twelve APP/PS1 male mice were randomized into four groups: APP/PS1 and low-, medium-, and high-dose Daotan Xixin Decoction. Three C57BL/6 wild-type mice were used as the control group. The learning and memory abilities of mice in each group were examined by the Morris water maze test. The pathological changes of hippocampal nerve cells were observed by hematoxylin-eosin staining and Nissl staining. Immunohistochemistry was employed to detect the expression of β-amyloid(Aβ)_(1-42) in the hippocampal tissue. The high-dose Daotan Xixin Decoction group with significant therapeutic effects and the model group were selected for high-throughput sequencing. The differentially expressed gene(DEG) analysis, Gene Ontology(GO) analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and Gene Set Variation Analysis(GSVA) were performed on the sequencing results. RT-qPCR and Western blot were conducted to determine the mRNA and protein levels, respectively, of some DEGs. Compared with the APP/PS1 group, Daotan Xixin Decoction at different doses significantly improved the learning and memory abilities of APP/PS1 mice, ameliorated the neuropathological damage in the CA1 region of the hippocampus, increased the number of neurons, and decreased the deposition of Aβ_(1-42) in the brain. A total of 1 240 DEGs were screened out, including 634 genes with up-regulated expression and 606 genes with down-regulated expression. The GO analysis predicted the biological processes including RNA splicing and protein folding, the cellular components including spliceosome complexes and nuclear spots, and the molecular functions including unfolded protein binding and heat shock protein binding. The KEGG pathway enrichment analysis revealed the involvement of neurodegenerative disease pathways, amyotrophic lateral sclerosis, and splicing complexes. Further GSVA pathway enrichment analysis showed that the down-regulated pathways involved nuclear factor-κB(NF-κB)-mediated tumor necrosis factor-α(TNF-α) signaling pathway, UV response, and unfolded protein response, while the up-regulated pathways involved the Wnt/β-catenin signaling pathway. The results of RT-qPCR and Western blot showed that compared with the APP/PS1 group, Daotan Xixin Decoction at different doses down-regulated the mRNA and protein levels of signal transducer and activator of transcription 3(STAT3), NF-κB, and interleukin-6(IL-6) in the hippocampus. In conclusion, Daotan Xixin Decoction can improve the learning and memory abilities of APP/PS1 mice by regulating the STAT3/NF-κB/IL-6 signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Male ; Alzheimer Disease/metabolism* ; Computational Biology ; Mice, Inbred C57BL ; High-Throughput Nucleotide Sequencing ; Amyloid beta-Protein Precursor/metabolism* ; Hippocampus/metabolism* ; Mice, Transgenic ; Presenilin-1/metabolism* ; Humans ; Memory/drug effects* ; Maze Learning/drug effects* ; Amyloid beta-Peptides/genetics* ; Disease Models, Animal

PURPOSE: Intertrochanteric fractures undergoing proximal femoral nail antirotation (PFNA) surgery are associated with significant hidden blood loss. This study aimed to explore whether intramedullary administration of tranexamic acid (TXA) can reduce bleeding in PFNA surgery for intertrochanteric fractures in elderly individuals. METHODS: A randomized controlled trial was conducted from January 2019 to December 2022. Patients aged over 60 years with intertrochanteric fractures who underwent intramedullary fixation surgery with PFNA were eligible for inclusion and grouped according to random numbers. A total of 249 patients were initially enrolled, of which 83 were randomly allocated to the TXA group and 82 were allocated to the saline group. The TXA group received intramedullary perfusion of TXA after the bone marrow was reamed. The primary outcomes were total peri-operative blood loss and post-operative transfusion rate. The occurrence of adverse events was also recorded. Continuous data was analyzed by unpaired t-test or Mann-Whitney U test, and categorical data was analyzed by Pearson Chi-square test. RESULTS: The total peri-operative blood loss (mL) in the TXA group was significantly lower than that in the saline group (577.23 ± 358.02 vs. 716.89 ± 420.30, p = 0.031). The post-operative transfusion rate was 30.67% in the TXA group and 47.95% in the saline group (p = 0.031). The extent of post-operative deep venous thrombosis and the 3-month mortality rate were similar between the 2 groups. CONCLUSION We observed that intramedullary administration of TXA in PFNA surgery for intertrochanteric fractures in elderly individuals resulted in less peri-operative blood loss and decreased transfusion rate, without any adverse effects, and is, thus, recommended.
Humans ; Tranexamic Acid/administration & dosage* ; Hip Fractures/surgery* ; Male ; Aged ; Female ; Fracture Fixation, Intramedullary/adverse effects* ; Blood Loss, Surgical/prevention & control* ; Antifibrinolytic Agents/administration & dosage* ; Aged, 80 and over ; Bone Nails ; Middle Aged ; Blood Transfusion/statistics & numerical data*

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

As the need for antibody production rises, there is an urgent need to lower the costs and enhance the efficiency of the separation process. Currently, the chromatographic media used for antibody separation and purification often focus on individual properties of antibodies, such as affinity, hydrophobicity, and charge, leading to issues like low purification efficiency or inadequate adsorption capacity. To address this, an electrostatically coupled polypeptide affinity medium (FD7-3, 5-diaminobenzoic acid n-sepharose, FD7-DA-Sepharose) was developed for rapid purification of antibodies from cell culture supernatant. This medium utilized 3, 5-diaminobenzoic acid as a spacer to attach the heptapeptide-affinity ligand (FYEILHD, FD7) to agarose microspheres. Antibodies could be adsorbed through charge interactions with the carboxyl functional group of the FD7-DA-Sepharose spacer, while FD7 enhanced electrostatic coupling and affinity adsorption through synergistic effects, significantly increasing the adsorption capacity while maintaining the affinity and specificity. The influences of pH and ionic strength on adsorption capacity were investigated with human immunoglobulin as a model protein. The static adsorption capacity (Q_m) of FD7-DA-Sepharose in the solution of pH 6.0 reached 67.73 mg/mL, representing a 52.68% increase compared with that (44.36 mg/mL) of the commercial Protein A affinity medium. Furthermore, the elution conditions for FD7-DA- Sepharose were mild (20 mmol/L PB, 0.5 mol/L NaCl, pH 6.0), in contrast to the harsh acidic elution (pH 2.7-3.6) typically associated with Protein A, which can damage antibody integrity. The FD7-DA-Sepharose medium was then employed to purify antibodies from cell culture supernatant, achieving the yield of 94.8% and the purity of 98.4%. The secondary structure of the purified antibody was determined by circular dichroism spectroscopy. The results demonstrated that FD7-DA-Sepharose enabled efficient purification of antibodies from cell culture supernatant, which provided a cost-effective solution (approximately one-third the price of commercial Protein A affinity medium) with gentle elution conditions that preserve the natural conformation of antibodies. This approach paves a novel, economical, and efficient way for the separation and purification of antibodies from cell culture supernatant.
Chromatography, Affinity/methods* ; Static Electricity ; Humans ; Sepharose/analogs & derivatives* ; Peptides/chemistry* ; Adsorption ; Antibodies/isolation & purification*

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To explore the correlations of evaluations of right heart function parameters in patients with Ebstein anomaly(EA)using echocardiography and cardiac MRI.Methods Data of transthoracic echocardiography and cardiac MRI in 32 patients with EA confirmed by operation were retrospectively analyzed.The correlations of cardiac cavity size,right ventricular function and strain parameters obtained using echocardiography and the functional right ventricular(fRV)ejection fraction(EF)measured using MRI were explored.Results MRI fRV-EF in 32 cases of EA was(23.20± 7.61)％.Among echocardiographic parameters in 32 cases of EA,fractional area change(FAC)of fRV(r=0.347,P=0.015)was slightly,while global longitudinal strain(GLS)of fRV(r=0.801,P＜0.001)was highly positively correlated with MRI fRV-EF,respectively,whereas atrialized right ventricle(aRV)area/fRV area(r=-0.730,P=0.007)was highly negatively,aRV area/left ventricular area(r=-0.450,P=0.042)and right ventricular anterior-posterior diameter(r=-0.650,P=0.022)were both moderately negatively correlated with MRI fRV-EF.Both the left ventricular eccentricity index(r=-0.347,P=0.049)and Glasgow outcome scale extended(r=-0.336,P=0.024)obtained with echocardiography were slightly negatively correlated MRI fRV-EF.Conclusion Right heart function parameters in EA patients obtained with echocardiography were correlated with those of MRI fRV-GLS,among which aRV area/fRV area were highly positively correlated with MRI fRV-EF,hence having great value for evaluating right heart function in EA patients.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective To investigate the clinical characteristics of asthma patients with deficiency of various viscera through the analysis of mitochondrial dysfunction and related influencing factors,and to explore the DDAH1/L-Arg/ADMA pathway as well as the trend of changes in the mitochondrial function and oxygen metabolism of the asthma patients through the analysis.Methods A total of 122 patients with acute exacerbation of bronchial asthma who met the inclusion criteria were selected,and their clinical data were collected.The patients were divided into 3 groups based on the criteria of visceral deficiency syndrome differentiation,namely lung qi deficiency group(47 cases),lung-spleen qi deficiency group(39 cases),and lung-spleen-kidney deficiency group(36 cases).Meanwhile,the normal control group including 44 cases was set up.For the asthma patients with visceral deficiency,an observation was conducted in the lung function indicators of forced expiratory volume in the first second(FEV1),the ratio of FEV1 to forced vital capacity(FEV1/FVC)and peak expiratory flow(PEF)as well as the severity of the disease.Moreover,venous blood was sampled from the patients for the detection of L-arginine(L-Arg)and asymmetric dimethylarginine(ADMA)levels with high-performance liquid chromatography coupled with mass spectrometry(HPLC-MS/MS),and for the detection of arginine metabolism related indicators of protein arginine methyltransferase 1(PRMT1)and dimethylarginine dimethylammonium hydrolysate 1(DDAH1)as well as the oxidative damage parameters of reactive oxygen species(ROS),thiobarbituric acid reactive substance(TBARS),8-iso-prostaglandins(8-iso),lipid peroxide(LPO),and malondialdehyde(MDA)with enzyme-linked immunosorbent assay(ELISA).The platelet mitochondria were extracted from asthma patients and normal controls,and then the mitochondrial membrane potential(MMP),adenosine triphosphate(ATP),and activities of cytochrome C oxidase(COX)in the platelet were determined by JC-1 flow cytometric assay in order to assess the mitochondrial function.The changes in the mitochondrial function and their influence on the mitochondrial function of asthma patients with deficiency of various viscera were analyzed and then compared with those of the normal control group.Results(1)There were statistically significant differences in the age and lung function(FEV1,FEV1/FVC,PEF)among asthma patients with deficiency of various viscera(P＜0.01):the age of the lung-spleen-kidney deficiency group was significantly older than that of the lung qi deficiency group and the lung-spleen qi deficiency group(P＜0.05),and the lung function(FEV1,FEV1/FVC,PEF)showed a significant downward trend with the aggravation of viscera deficiency(P＜0.05).(2)There was a statistically significant difference in the illness grading of patients with deficiency of various viscera(P＜0.01).In the lung qi deficiency group,the illness status was predominated by intermittent state of asthma(grade 1),accounting for 65.96%,and then followed by mild asthma(grade 2),accounting for 25.53%.In the lung-spleen qi deficiency group,the illness status was predominated by moderate asthma(grade 3),accounting for 41.03%,and then followed by intermittent state of asthma(grade 1),accounting for 30.77%.In the lung-spleen-kidney deficiency group,the illness status was predominated by severe asthma(grade 4),accounting for 52.78%,and then followed by moderate asthma(grade 3),accounting for 33.33%.It is indicated that with the aggravation of viscera deficiency,the severity of asthma tended to be aggravated.(3)There were significant differences in plasma 8-iso,ROS,LPO and MDA levels between asthma patients with deficiency of various viscera and normal control group(P＜0.05).The plasma 8-iso and LPO levels of the asthma patients with deficiency of various viscera and the plasma MDA and ROS levels of asthma patients with lung-spleen qi deficiency and lung-spleen-kidney deficiency were significantly higher than those in normal control group(P＜0.05),and the plasma ROS level of asthma patients with lung-spleen qi deficiency and lung-spleen-kidney deficiency was significantly higher than that in asthma patients with lung qi deficiency(P＜0.05).The plasma TBARS level of asthma patients with deficiency of various viscera tended to be higher than that of normal control group,but the difference was not statistically significant(P＞0.05).It is indicated that reactive oxygen species and peroxide lipids accumulated in the body of asthma patients with deficiency of various viscera,and their levels increased with the aggravation of visceral deficiency.(4)The levels of MMP,ATP and COX in asthma patients with deficiency of various viscera were significantly lower than those in normal control group(P＜0.05),and the activity of COX decreased with the aggravation of visceral deficiency.(5)The levels of plasma L-Arg,L-Arg/ADMA and DDAH1 in asthma patients with deficiency of various viscera were significantly lower than those in normal control group(P＜0.05),and their levels decreased gradually with the aggravation of visceral deficiency.There was no significant difference in the plasma ADMA and PRMT1 levels between asthma patients with deficiency of various viscera and normal control group(P＞0.05).Conclusion It is indicated that the visceral deficiency in asthma patients is consistent with the progression of illness status,oxygen metabolism and its influencing factors,and the degree of oxidative damage.It is suggested that the progression of illness status can be judged by visceral deficiency in traditional Chinese medicine according to the parameters of body metabolism.

Objective To report the clinical and imaging characteristics of a case with the clinical manifestation of multiple lung and liver nodules,diagnosed as IgG4-related hepatic inflammatory pseudotumor(HIPT)complicated by hepatic tissue-infection,and review the literature in order to facilitate clinical diagnosis and differential identification of IgG4-related HIPT.Methods A retrospective analysis was conducted on the medical records of a patient with IgG4-related disease(IgG4-RD)characterized by multiple lung and liver nodules.A literature review was performed by searching Chinese and English databases to summarize the clinical and imaging characteristics of IgG4-related HIPT and hepatic tissue infection.Results The case involved a 64-year-old female admitted to the Rheumatology and Immunology Department of the First Medical Center of Chinese PLA General Hospital due to"poor appetite and fatigue for over a year,and dry cough for four months".She presented with multiple nodules in the lungs and liver,without involvement of the eyelids,salivary glands,submandibular glands,or pancreas.Laboratory test results revealed elevated serum IgG4 levels at 14.1 g/L and C-reactive protein(CRP)at 82.1 mg/L.Pulmonary CT scans indicated multiple solid nodules in both lungs with clear boundaries.Abdominal contrast-enhanced MRI revealed a nodule in liver segment S7 with a pseudocapsule around it,clear boundaries,and uniform enhancement;another nodule in liver segment S5 with blurred boundaries and ring enhancement.The final diagnosis of the liver nodules was confirmed by pathological and metagenomic sequencing to be an IgG4-related HIPT in segment S7 and hepatic tissue infection in segment S5.After a full course of anti-infection and treatment with methylprednisolone and leflunomide,follow-up imaging showed near-complete resolution of the lung and liver nodules.Literatures were searched in China National Knowledge Infrastructure(CNKI),Wanfang,and PubMed databases(up to September 2023),and no case of IgG4-RD complicated with both liver involvement and infection was found.A total of 26 cases of IgG4-RD involving the liver have been reported so far,predominantly in males(92.3%),with an average age of 51 years.Most patients presented with abnormal liver function as the initial symptom,with normal blood inflammatory markers.Imaging typically shows a single nodule in 88.5%of cases,with clear boundaries and uniform enhancement,as well as ring enhancement.Concurrent involvement of the pancreas and biliary tract is common.Pathology is the gold standard for confirming the disease.Conclusions This case reports coexistence of IgG4-related HIPT and infection within multiple hepatic nodules.In the diagnosis and treatment of patients with IgG4-RD presenting with multiple hepatic nodules,if the imaging characteristics of the nodules are inconsistent,it is necessary to consider the possibility of the underlying disease coexisting with other conditions,which can be easily misdiagnosed.Actively obtaining pathological tissue is crucial for aiding in the definitive diagnosis.