Age-related macular degeneration(ARMD)is a progressive visual impairment fundus disease that frequently occurs in individuals aged >55 years. The main risk factors are aging, long-term smoking, genetics, and racial differences. Pathogenesis includes abnormal function of the retinal pigment epithelium, damaged blood-retinal barrier, and abnormal immune function. Currently, intravitreal injection(IVI)of anti-vascular endothelial growth factor(VEGF)drugs is the preferred treatment option for ARMD in clinical practice. However, it also faces challenges such as repeated treatments, high medical costs, and poor patient compliance. The predicament in the treatment of ARMD has given rise to several new treatment options. This article aims to review the treatment methods and progress of dry ARMD and wet ARMD, providing new ideas for addressing the limitations of the current clinical anti-VEGF treatment.

ObjectiveThis study aimed to investigate the optimal compatibility ratio of the Chuanxiong Rhizoma-Carthami Flos （CR-CF） couplet medicines in ischemic stroke （IS） therapy and its pharmacological action mechanism， providing a scientific basis for the clinical application of CR-CF couplet medicines in IS therapy. MethodsThe chemical composition of CR-CF was analyzed using liquid chromatography mass spectrometry （LC-MS/MS）. The contents of eight characteristic chemical components in aqueous extracts of CR-CF with common clinical compatibility ratios （1∶1， 1∶2， 1∶3， 3∶2， 2∶1） were determined by ultra-high performance liquid chromatography（UHPLC）. An oxygen-glucose deprivation/reoxygenation （OGD/R）-induced mouse hippocampal neuron HT22 cell injury model was established， and cells were treated with different CR-CF compatibility ratios. The collaborative index （CI） was calculated by using CompuSyn software. A cerebral artery occlusion/reperfusion （MCAO/R） model of rats was induced by using the modified Longa suture method. The rats were divided into the sham group， model group， Chuanxiong Rhizoma （CR） group （1.3 g·kg^-1）， Carthami Flos （CF） group （3.9 g·kg^-1）， CR-CF group （5.2 g·kg^-1）， and edaravone group （5 mg·kg^-1）. Neuronal defect scores were assessed by the Longa scoring method. Cerebral infarction volume was measured by 2，3，5-triphenyltetrazolium chloride（TTC） staining. Neuronal damage was observed via hematoxylin-eosin （HE） staining. Neuronal apoptosis of rats was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining， and the expression of apoptosis-related proteins was analyzed by Western blot. Label-free proteomics was employed to screen differentially expressed proteins， and Western blot was used to examine the expression of phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway-related proteins. Finally， molecular docking was performed to predict the binding affinity of eight active constituents in CR-CF （1∶3） with PI3K. ResultsWhen CR-CF was combined at a 1∶3 ratio， the total content of the eight active constituents in the extract was the highest， and the synergistic protective effect on OGD/R-injured HT22 cells was the strongest （CI=0.308）. Animal experiments showed that compared with the sham group， the model group exhibited increased neuroecological score points （P<0.01）， larger cerebral infarction volumes （P<0.01）， aggravated brain tissue damage， elevated neuronal apoptosis （P<0.01）， and increased B-cell lymphoma-2（Bcl-2）-associated X protein （Bax）/Bcl-2 and cleaved Cysteinyl aspartate specific proteinase-3/Cysteinyl aspartate specific proteinase-3 （cleaved Caspase-3/Caspase-3） ratios （P<0.01）. Compared with the model group， CR-CF （1∶3） significantly reduced neurological scores （P<0.01）， significantly decreased cerebral infarction volume （P<0.01）， alleviated brain tissue damage， inhibited neuronal apoptosis （P<0.01）， and significantly lowered the Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 ratios （P<0.01）. The therapeutic effect of CR-CF （1∶3） was superior to that of CR or CF alone. Proteomic analysis revealed that CR-CF （1∶3） activated the PI3K/Akt signaling pathway. Validation experiments demonstrated that compared with the sham group， the model group showed obviously reduced p-PI3K/PI3K and p-Akt/Akt （P<0.05）. Compared with the model group， p-PI3K/PI3K and p-Akt/Akt ratios （P<0.05） obviously increased. Compared with the CR-CF group， the 2-（4-morpholinyl）-8-phenyl-4H-1-benzopyran-4-one LY294002 inhibitor+CR-CF group exhibited obviously decreased p-PI3K/PI3K and p-Akt/Akt （P<0.05）. Molecular docking results indicated that the active constituents of CR-CF （1∶3） had strong binding affinity with PI3K. ConclusionThe CR-CF couplet medicines at a 1∶3 ratio exhibit optimal synergistic effects， and their anti-IS mechanism is closely related to activation of the PI3K/Akt signaling pathway and inhibition of neuronal apoptosis.

[Objective] To study on the genotyping of a sample with inconsistent forward and reverse serological tests, and to conduct a pedigree investigation and molecular biological mechanism study. [Methods] The ABO blood group of the proband and his family members were identified using blood group serological method. The ABO gene exon 1-7 of samples of the proband and his family were sequenced by Sanger and single molecule real-time sequencing (SMRT). DeepTMHMM was used to predict and analyze the transmembrane region of proteins before and after mutation. [Results] The proband and his mother have the Bw phenotype, while his maternal grandfather has ABw phenotype. The blood group results of forward and reverse typing of other family members were consistent. ABO gene sequencing results showed that there was B new mutation of c.3 G>C in exon 1 of ABO gene in the proband, his mother and grandfather, leading to a shift in translation start site. DeepTMHMM analysis indicated that the shift in the translation start site altered the protein topology. [Conclusion] The c.3G>C mutation in the first exon of the ABO gene leads to a shift in the translation start site, altering the protein topology from an α-transmembrane region to a spherical signaling peptide, reducing enzyme activity and resulting in the Bw serological phenotype.

ObjectiveINF2 is a member of the formins family. Abnormal expression and regulation of INF2 have been associated with the progression of various tumors, but the expression and role of INF2 in hepatocellular carcinoma (HCC) remain unclear. HCC is a highly lethal malignant tumor. Given the limitations of traditional treatments, this study explored the expression level, clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets. MethodsIn this study, we used public databases to analyze the expression of INF2 in pan-cancer and HCC, as well as the impact of INF2 expression levels on HCC prognosis. Quantitative real time polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues. The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples. Subsequently, the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments. Finally, the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments. ResultsINF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival, liver cirrhosis and pathological differentiation of HCC patients. The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC. In vivo and in vitro HCC models, upregulated expression of INF2 triggers the proliferation and migration of the HCC cell, while knockdown of INF2 could counteract this effect. INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression, thus promoting tumor progression. ConclusionINF2 is highly expressed in HCC and is associated with poor prognosis. High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression, and targeting INF2 may be beneficial for HCC patients with high expression of INF2.

This paper summarizes clinical experience in treating depression with a combined approach of acupuncture and herbal medicine under the guiding principle of deficiency and excess. Given the complex pathogenesis of depression， it is proposed that syndrome differentiation based on deficiency and excess should serve as the overarching principle. Acupuncture is prioritized， supplemented by Chinese herbal medicine. Acupuncture is based on the spirit-regulating protocol； for excess syndromes， it is combined with the calming and restoring protocol， while for deficiency syndromes， it is combined with the five zang organs tonification protocol. In cases of mixed deficiency and excess， the two protocols are alternated， and adjustments are made dynamically throughout the treatment based on syndrome evolution. Herbal prescriptions are also guided by the differentiation of deficiency and excess. For excess patterns， dispersion and clearance should be emphasized， focusing on soothing the liver， clearing heat， relieving irritability， regulating qi， transforming phlegm， and calming the mind； for deficiency patterns， tonification is emphasized， aiming to strengthen the spleen， nourish the blood， calm the spirit， tonify qi， and consolidate the root.

AIM:To evaluate the efficacy of intravitreal ranibizumab injection(IVR)combined with subthreshold micropulse(STMP)in the treatment of diabetic macular edema(DME).METHODS: Retrospective study. A total of 98 DME patients(98 eyes)admitted to our hospital from March 2022 to March 2023 were enrolled and divided into two groups based on treatment methods: the control group(49 eyes)received STMP yellow laser therapy alone, while the study group(49 eyes)underwent combined IVR and STMP yellow laser therapy. Comparisons were made between the two groups regarding best corrected visual acuity(BCVA), retinal neovascularization(RNV)leakage area, parafoveal macular thickness(PMT), foveal macular thickness(FMT), central retinal thickness(CRT), and foveal avascular zone(FAZ)area, quality of life was assessed using the Chinese-version low vision quality of life questionnaire(CLVQOL), and complication rates were recorded. Additionally, serum levels of nitric oxide synthase(NOS)and vascular endothelial growth factor(VEGF)were measured before and after treatment in both groups.RESULTS: At 3 mo after treatment, both groups showed improved BCVA compared to baseline, with reduced RNV leakage area, PMT, FMT, CRT, FAZ, and serum levels of VEGF, while serum NOS levels and all CLVQOL domain scores were higher than pre-treatment(all P<0.05). Furthermore, the study group demonstrated superior outcomes in all these parameters compared to the control group(all P<0.05), and no ocular or systemic complications occurred in any patient.CONCLUSION: IVR combined with STMP yellow laser for DME improves visual acuity, reduces RNV leakage area, PMT, FMT, CRT, and FAZ, modulates serum NOS and VEGF levels, enhances quality of life, and demonstrates good safety.

Objective To investigate the seroprevalence of antibody against Toxoplasma gondii among patients with hematological malignancies, and compare it with that among health individuals, so as to provide insights into unraveling the pathogenesis of hematological malignancies. Methods A total of 225 patients with hematological malignancies in Department of Hematology, Xuzhou Central Hospital and 300 healthy individuals in the same hospital were enrolled from 2017 to 2024. Blood samples were collected from all subjects, and the serum IgG and IgM antibodies against T. gondii were detected using chemiluminescent immunoassay. Demographic and clinical features were collected from patients with hematological malignancies, including gender, age, contact with cats, consumption of raw or undercooked meat, type of malignancy, clinical symptoms, blood transfusion and treatment, and the seroprevalence of anti-T. gondii antibody was compared among patients with different characteristics. Results The age (t = 0.72, P > 0.05) and gender (χ² = 0.93, P > 0.05) were compared between patients with hematological malignancies and healthy individuals. The seroprevalence of T. gondii infection was 20.89% among patients with hematological malignancies and 4.33% among healthy individuals (χ² = 34.81, P < 0.01), and the seroprevalence of anti-T. gondii IgG antibody was 20.89% among patients with hematological malignancies and 4.33% among healthy individuals (χ² = 34.81, P < 0.01), while there was no significant difference in the seroprevalence of anti-T. gondii IgM antibody between patients with hematological malignancies and healthy individuals (1.33% vs. 0; corrected χ² = 2.02, P > 0.05). The seroprevalence of T. gondii infection was 23.08% among patients with leukemia, 16.67% among patients with lymphoma, 19.23% among patients with multiple myeloma, 24.00% among patients with myeloproliferative neoplasm, and 26.09% among patients with myelodysplastic syndrome (χ² = 1.44, P > 0.05), and was all higher than among healthy individuals (corrected χ² = 23.92, 10.74, 13.76, 12.84 and 14.54; all P values < 0.01). In addition, there were no significant differences in the detection of anti-T. gondii antibody among patients with hematological malignancies in terms of gender, age, contact with cats, consumption of raw or undercooked meat, chemotherapy or blood transfusion (χ² = 0.76, 1.97, 0, 2.81, 2.38 and 0.66; all P values > 0.05). Conclusions There is a high risk of T. gondii infection among patients with hematological malignancies, and intensified surveillance of T. gondii infection is recommended among patients with hematological malignancies.

ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease （CAD） complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized， double-blind， and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group， with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo， respectively， both in combination with conventional Western medication. The dose was 45.0 mg， three times daily， for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire （SAQ） scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine （TCM） syndrome score， the patient health questionnaire-9 （PHQ-9）， generalized anxiety disorder-7 （GAD-7）， inflammatory markers ［interleukin-18 （IL-18）， interleukin-10 （IL-10）， tumor necrosis factor-alpha （TNF-α）， CD40， etc.］， monoamine neurotransmitters ［e.g.， dopamine （DA）］， vascular endothelial function markers ［e.g.， endothelin-1（ET-1）］， adipokines， and ischemia-modified albumin （IMA）. Adverse reactions were also recorded. ResultsA total of 92 patients completed the study， with 44 in the observation group and 48 in the control group. Compared with baseline， both groups showed significant decreases in PHQ-9， GAD-7， and TCM syndrome scores following treatment （P<0.05）， along with a significant increase in SAQ scores （P<0.05）. In the observation group， DA levels were significantly increased （P<0.05）， while levels of IL-18， TNF-α， CD40， ET-1， and IMA were decreased （P<0.05）. In contrast， the control group exhibited significantly increased CD40 levels （P<0.05）. Compared with the control group after treatment， the observation group showed significant improvements in the SAQ dimensions of physical limitation， angina stability， treatment satisfaction， and disease perception， as well as in TCM syndrome score， PHQ-9 score， IL-18， CD40， ET-1， and IMA （P<0.05）. No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression， alleviate angina symptoms， and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation， improvement of vascular endothelial function， reduction of IMA， and increase of monoamine neurotransmitter levels.

ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease （CAD） complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized， double-blind， and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group， with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo， respectively， both in combination with conventional Western medication. The dose was 45.0 mg， three times daily， for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire （SAQ） scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine （TCM） syndrome score， the patient health questionnaire-9 （PHQ-9）， generalized anxiety disorder-7 （GAD-7）， inflammatory markers ［interleukin-18 （IL-18）， interleukin-10 （IL-10）， tumor necrosis factor-alpha （TNF-α）， CD40， etc.］， monoamine neurotransmitters ［e.g.， dopamine （DA）］， vascular endothelial function markers ［e.g.， endothelin-1（ET-1）］， adipokines， and ischemia-modified albumin （IMA）. Adverse reactions were also recorded. ResultsA total of 92 patients completed the study， with 44 in the observation group and 48 in the control group. Compared with baseline， both groups showed significant decreases in PHQ-9， GAD-7， and TCM syndrome scores following treatment （P<0.05）， along with a significant increase in SAQ scores （P<0.05）. In the observation group， DA levels were significantly increased （P<0.05）， while levels of IL-18， TNF-α， CD40， ET-1， and IMA were decreased （P<0.05）. In contrast， the control group exhibited significantly increased CD40 levels （P<0.05）. Compared with the control group after treatment， the observation group showed significant improvements in the SAQ dimensions of physical limitation， angina stability， treatment satisfaction， and disease perception， as well as in TCM syndrome score， PHQ-9 score， IL-18， CD40， ET-1， and IMA （P<0.05）. No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression， alleviate angina symptoms， and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation， improvement of vascular endothelial function， reduction of IMA， and increase of monoamine neurotransmitter levels.

Objective: To explore the association between negative life events and smartphone addiction among middle school students, so as to provide theoretical support and practical guidance for prevention and intervention of smartphone addiction among middle school students. Methods: Using cluster sampling, 8 890 students were selected to survey from 27 junior high schools and 3 senior high schools in a district of Shenzhen in 2022 (baseline) and 2023 (followup). Data were collected through selfresigned questionnaires on basic information, the Smartphone Addiction Scale-Short Version, and the Adolescent Selfrating Life Events Checklist. Mixedeffects models were employed to analyze the association. Results: Compared to 2022, the punishment scores of middle school students in 2023 [1.00 (0.00, 6.00) and 1.00 (0.00, 6.00)] decreased (Z=4.27), while the scores of interpersonal stress, learning stress and adaptation [4.00(0.00, 8.00), 4.00(0.00, 8.00); 4.00(1.00, 8.00), 5.00(2.00, 9.00); 2.00 (0.00, 6.00), 3.00 (0.00, 7.00)] increased (Z=-3.04, -8.36, -6.80) (P<0.01). Mixedeffects models revealed a positive doseresponse relationship between negative life events and smartphone addiction (OR=1.08-1.17, P<0.01). Stepwise regression showed independent positive effects of interpersonal stress (OR=1.05), academic stress (OR=1.03), and adaptation stress (OR=1.11) on smartphone addiction (P<0.01). Subgroup analysis of nonaddicted students in 2022 confirmed persistent associations for academic stress (OR=1.03) and adaptation (OR=1.07) (P<0.01). Conclusion Negative life events exhibit a positive doseresponse relationship with smartphone addiction, particularly interpersonal stress, academic stress, and adaptationrelated events.