AIM: To evaluate whether Wnt pathway-related genes previously implicated in high myopia(HM)could serve as candidate genes for HM in the Chinese Han population, and to identify risk loci associated with HM susceptibility.METHODS: A case-control association analysis was conducted, involving 530 HM patients(HM group)and 1 087 healthy controls. The test efficacy was estimated using Quanto software. Peripheral blood DNA was extracted using the magnetic bead method, and seven candidate single nucleotide polymorphisms(SNPs)were genotyped using the Sequenom MassARRAY system, including HIVEP3 rs17365632, rs35134694, rs11210537, CTNNB1 rs13072632, CAMK2N1 rs10753502, TCF4 rs41396445 and Wnt7B rs73175083. Differences in allele and genotype frequencies between the HM and healthy control groups were compared under different inheritance models. Haplotype analysis was performed using SHEsis plus.RESULTS: All 7 SNPs had a genotyping detection rate exceeding 90%, and were in Hardy-Weinberg equilibrium(P>0.05). The test efficacy of the sample size was above 90.13%, indicating that the samples were representative of the population. In the HM group, the A allele frequency of HIVEP3 rs11210537 was significantly reduced(Pc=0.003, OR=0.889). Conversely, the G allele frequency was significantly elevated(Pc=0.003, OR=1.176). In an additive genetic model(AA vs GG), the AA genotype frequency was significantly lower than the GG genotype frequency(Pc=0.003, OR=0.583). Additionally, the frequency of the CCA haplotype of rs17365632, rs35134694, and rs11210537 in HIVEP3 was decreased in the HM group compared to the control group(Pc=0.008, OR=0.791).CONCLUSION: The SNP locus rs11210537 in the HIVEP3 gene is associated with genetic susceptibility to HM in the Chinese Han population, with the G allele identified as risk genetic markers. The CCA haplotype of rs17365632, rs35134694, and rs11210537 in the HIVEP3 gene represents a protection haplotype for HM.

Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored. Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD's direct target. ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 via the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD's therapeutic efficacy against METH addiction. Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO-A1R signaling pathway.

The level of urinary albumin is a critical indicator for the early diagnosis and management of chronic kidney disease (CKD). However, existing methods for detecting albumin are not conducive to point-of-care testing due to the complexity of reagent addition and incubation processes. This study presents a smartphone-integrated handheld automated biochemical analyzer (sHABA) designed for point-of-care testing of urinary albumin. The sHABA features a pre-loaded, disposable reagent cassette with reagents for the albumin assay arranged in the order of their addition within a hose. The smartphone-integrated analyzer can drive the reagents following a preset program, to enable automatic sequential addition. The sHABA has a detection limit for albumin of 5.9 mg/L and a linear detection range from 7 to 450 mg/L. The consistency of albumin level detection in 931 urine samples using sHABA with clinical tests indicates good sensitivity (95.78%) and specificity (90.16%). This research advances the field by providing an automated detection method for albumin in a portable device, allowing even untrained individuals to monitor CKD in real time at the patient's bedside. In the context of promoting tiered diagnosis and treatment, the sHABA has the potential to become an essential tool for the early diagnosis and comprehensive management of CKD and other chronic conditions.

The pathogenesis theory of"spleen deficiency and stasis toxin"in gastric cancer holds that spleen is the source of generation and transformation of qi and blood,that spleen deficiency is the internal basis of disease and throughout the disease.Stasis toxin is based on spleen deficiency,which is the fundamental pathogenesis of gastric cancer.In the pathological process of gastric cancer,a variety of metabolic substances in tumor cells and tumor microenvironment,mainly glucose metabolic reprogramming,undergo metabolic changes to reconstruct the phenotype and function of tumor-related macrophages,which is consistent with the pathogenesis theory of"spleen deficiency and stasis toxin".Therefore,this article focused on the reprogramming of glucose metabolism in tumor microenvironment to drive the phenotypic remodeling of tumor-related macrophages,explored the scientific connotation of the pathogenesis theory of"spleen deficiency and stasis toxin"of gastric cancer,and provided references for the theoretical and clinical research on the treatment of gastric cancer by TCM.

Objective:To evaluate main performance indexes and application value of a domestic blood nucleic acid test system for blood screening,so as to ensure the safety of blood screening in the system of blood bank.Methods:Twenty samples were selected from Langfang Center Blood Bank in January 2022,and 6703 blood specimens of voluntary blood donors from Langfang Blood Bank between 2022 and 2023 were simultaneously selected.According to the requirements of the"Technical Operating Procedures for Blood Stations(2019 Edition)"and the standard for medical medicine industry"Nucleic Acid Amplification Test Reagents(kits)",the performances of stability,analytical specificity,sensitivity,precision,anti-interference ability and against cross-contamination ability of nucleic acid test system were verified for the analysis of clinical application.Results:The coincidence rate of the nucleic acid test system was 100%for 20 negative plasma samples.The coincidence rates of the sensitivities of Hepatitis B virus deoxyribonucleic acid(HBV DNA),Hepatitis C virus ribonucleic acid(HCV RNA)and Human immunodeficiency virus ribonucleic acid(1+2)(HIV 1+2 RNA)were respectively 100%,and percentages of the coefficient of variation(CV%)of the precision of them were respectively 1.57%,0.75%and 1.49%.When the system conducted nucleic acid test,the hemolytic plasma with a hemoglobin concentration level of 400mg/dl and the blood specimen with triglyceride concentration levels of 3 000 mg/dl did not affect the analysis performances of the standard substances of HBV-DNA(9.0 IU/ml),HCV-RNA(30.0 IU/ml)and HIV-RNA(135.0 IU/ml)of low concentration level.There were not cross-contaminations when 10 positive samples at high concentration(1 000 IU/ml)were cross-lined with 11 negative samples to conduct test.A total of 16(0.24%)reactive specimens were checked out from 6 703 specimens by Nucleic Acid Test(NAT)Technique under mixed mode.Conclusion:Nucleic acid test system must conduct performance verification before it is put into use,so as to ensure the safety of blood screening.The currently domestic nucleic acid test system can meet the requirements of screening blood safety.The performance verification of nucleic acid test system has great value in ensuring the safety of blood screening.

Refractory acute T-lymphoblastic leukemia (T-ALL), which is characterized by a low sensitivity to conventional induction therapy and poor prognosis, poses significant challenges during treatment. This study reported a case of refractory T-ALL patient with mutations in the JAK1, JAK3, and STAT5B genes from Nanjing University’s Gulou Hospital. Following an unsuccessful course of standard VDLP regimen chemotherapy, the treatment was modified to include ruxolitinib in combination with venetoclax and azacitidine. Subsequent to this therapy, the patient achieved bone marrow minimal residual disease (MRD) negativity. Notably, pleural effusion and mediastinal mass significantly improved the post-chest cavity infusion of dexamethasone combined with etoposide at the same stage. The patient also underwent allogeneic hematopoietic stem cell transplantation upon achieving bone marrow remission and was followed up until January 2024. Ruxolitinib combined with venetoclax and azacytidine has shown promising efficacy and safety in treating refractory T-ALL harboring the JAK1, JAK3, and STAT5B mutations, providing a novel therapeutic approach for such patients.

Objective To evaluate the corneal biomechanical changes after femtosecond laser-assisted in situ kerato-mileusis(FS-LASIK)combined with accelerated corneal cross-linking(FS-LASIK Xtra)for the correction of high myopia u-sing Corvis ST.Methods In this prospective case-control study,185 patients(185 eyes)who underwent surgical correc-tion of high myopia in the Affiliated Eye Hospital of Shandong University of Chinese Medicine from July 2020 to July 2022 were selected,including 93 patients receiving FS-LASIK Xtra in the FS-LASIK Xtra group and 92 patients receiving FS-LASIK in the FS-LASIK group.All patients had their right eyes included in the study.During the 6-month follow-up,the uncorrect-ed visual acuity,spherical equivalent(SE),mean corneal curvature,thinnest corneal thickness,corneal biomechanical pa-rameters[deformation amplitude ratio at 2 mm(DAR 2 mm),integrated radius(IR),stiffness parameter at the first appla-nation(SP-A1),stress-strain index(SSI)],and changes in corneal biomechanical parameters before and after surgery(difference between 6 months after surgery and before surgery,namely ΔDAR 2 mm,ΔIR,ΔSP-A1,and ΔSSI)were recor-ded.Independent sample t test and Mann-Whitney U test were used to compare the data between groups.Results Three months after surgery,the SE in the FS-LASIK group and the FS-LASIK Xtra group was(-0.21±0.31)D and(-0.04±0.36)D,respectively,and the difference was statistically significant(t=3.49,P=0.001).Six months after surgery,the SE in the FS-LASIK group and the FS-LASIK Xtra group was(-0.33±0.31)D and(-0.14±0.37)D,respectively,and the difference was statistically significant(t=4.00,P＜0.001).There was no significant difference in efficacy index and safety index between the FS-LASIK group and the FS-LASIK Xtra group at 6 months after operation(both P＞0.05).There were no significant differences in DAR 2 mm,IR,SP-A1,SSI and other biomechanical parameters between the two groups before surgery(all P＞0.05).At 6 months postoperatively,ΔIR in the FS-LASIK group and the FS-LASIK Xtra group was 3.03±0.78 and 2.67±0.80,respectively;ΔSP-A1 was-35.93±12.04 and-30.43±12.44,respectively;and ΔSSI was-0.09±0.10 and-0.03±0.06,respectively.The differences between the two groups were all statistically significant(all P＜0.05).Conclusion FS-LASIK Xtra for correction of high myopia improves the stability of postoperative visual acuity and SE with good safety and efficacy,but reduces the stability of comeal biomechanical parameters compared with before surgery;still,it is better than conventional FS-LASIK,and the long-term effect needs to be further assessed.

Erythrocytes-camouflaged nanoparticles is an in vivo delivery system that uses erythrocytes or erythrocyte membrane nano vesicles as carriers for drugs, enzymes, peptides and antigens. This system has the advantages of good biocompatibility, long circulation cycle and efficient targeting. This review summarizes the type of carriers, their development history, the application of delivery strategies as well as their limitations and future challenges. Lastly, future directions and key issues in the development of this system are discussed.
Pharmaceutical Preparations ; Drug Delivery Systems ; Vaccines ; Erythrocytes ; Nanoparticles

Objective:To study the clinical and molecular characteristics of a family with familial hypercholesterolemia (FH) with LDLRAP1 and ABCG8 gene abnormality.Methods:In September 2020, one case of FH was included in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; peripheral venous blood samples of members of the family were collected to detect serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) indicators; use high-performance liquid chromatography to detect serum stigmasterol and sitosterol content; perform second-generation gene sequencing to detect gene mutations in probands and family members; use Pymol software to detect gene mutations point for pathogenicity analysis, and use Uniprot Modelling software to perform protein structure modeling.Results:The patient presented with anemia, multiple xanthomas and early-onset acute coronary syndrome. The coronary angiography showed severe coronary artery lesions; abdominal ultrasound showed splenomegaly; blood smear showed shaped erythrocytes and large platelets. The level of serum TC, LDL-C, stigmasterol and sitosterol was 8.54 mmol/L (2.3-5.7 mmol/L), 4.84 mmol/L (range of normal value 1.3-4.3 mmol/L), 44 μmol/L (1.0-10 μmol/L), 28 μmol/L (1.0-15 μmol/L), respectively; LDLRAP1 gene mutation was found: exon4 c.415C>T:p.Q139X; the truncated protein formed by this homozygous mutation lost multiple stable protein structure regions, which can not have a normal function. At the same time, ABCG8 gene mutations were also found: exon13 c.1895T>C (p.V632A) and exon8 c.1199C>A:p.T400K . Two cases of family members had a mild increase in HDL-C (Ⅱ5: 2.33 mmol/L, Ⅱ6∶2.96 mmol/L), 3 cases carrying the ABCG8 gene mutations had a slight increase in stigmasterol (Ⅱ8: 23 μmol/L, Ⅱ7: 24 μmol/L, Ⅰ2: 18 μmol/L) and sitosterol (Ⅱ8: 41 μmol/L, Ⅱ7: 33 μmol/L, Ⅰ2: 45 μmol/L), suggesting that its association with the concentration of plant sterols. Conclusions:FH patients with LDLRAP1 and ABCG8 gene abnormalities may have abnormal plant sterol concentrations, and their clinical manifestations are more complicated. Therefore, family history, LDL-C, plant sterol levels, and genetic test results should be considered comprehensively.

AIM: To study the polymorphism distribution of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes and their influence on serum homocysteine (Hcy) concentration. METHODS: A total of 148 patients diagnosed with ischemic stroke from November 2020 to February 2021 in Yijishan Hospital of Wanan Medical College were selected for the study, and patients were typed for MTHFR 677C/T and MTRR 66A/G genes using fluorescent staining in situ hybridization technique. Serum Hcy concentrations were measured in 21 patients using a circulating enzyme assay. The distribution of MTHFR 677C/T and MTRR 66A/G gene polymorphisms were analyzed, and the differences in serum Hcy concentrations between patients with different genotypes were compared. RESULTS: The mutation rates of MTHFR 677C/T and MTRR 66A/G genes were 42.57% and 26.01%, respectively, and no significant differences in gene distribution frequencies were observed between men and women (P>0.05). The mean Hcy serum concentration was (16.04±4.34) μmol/L in 21 patients, including 8 patients (38.10%) with <15 μmol/L and 13 patients (61.90%) with ≥15 μmol/L. The Hcy serum concentrations in patients with different genotypes of MTHFR were TT (18.91±5.34) μmol/L, CT (14.38±1.84) μmol/L and CC (13.58±2.86) μmol/L, respectively, and were statistically different (P<0.001). Serum Hcy concentrations in patients with different genotypes of MTRR were not statistically different (P>0.05). CONCLUSION: MTHFR gene polymorphisms can affect serum Hcy concentrations. The MTHFR genotyping can be considered for individualized folic acid supplement. This conclusion should be further verified by expanding the clinical sample size.