Objective Hippocampal atrophy is a clinically important marker for the diagnosis of many psychiatric disorders such as Alzheimer’s disease‚ so accurate segmentation of the hippocampus is an important scientific issue. With the development of deep learning‚ a large number of advanced automatic segmentation method have been proposed. However‚ 3D hippocampal segmentation is still challenging due to the effects of various noises in MRI and unclear boundaries between various classes of the hippocampus. Therefore‚ the aim of this paper is to propose new method to segment the hippocampal head‚ body‚ and tail more accurately. Methods To overcome these challenges‚ this paper proposed two strategies. One was the spatial and frequency domain features adaptive fusion strategy‚ which reduced the influence of noise on feature extraction by automatically selecting the appropriate frequency combination through fast Fourier transform and convolution. The other was an inter-class boundary region enhancement strategy‚ which allowed the network to focus on learning the boundary regions by weighting the loss function of the boundary regions between each class to achieve the goal of pinpointing the boundaries and regulating the size of the hippocampal head‚ body and tail. Results Experiments performed on a 50-case teenager brain MRI dataset show that our method achieves state-of-the-art hippocampal segmentation. Hippocampal head‚ body and tail had been improved compared to the existing method. Ablation experiments demonstrated the effectiveness of our two proposed strategies‚ and we also validated that the network had a strong generalization ability on a 260-case Task04_Hippocampus dataset. It was shown that the method proposed in this paper could be used in more hippocampal segmentation scenarios. Conclusion The method proposed in this paper can help clinicians to observe hippocampal atrophy more clearly and accomplish more accurate diagnosis and follow-up of the condition.

Objective:To explore the diagnostic value of serum cystatin C (CysC) and C1q tumor necrosis factor-related protein 9 (CTRP9) levels for diabetic retinopathy (DR) and diabetic macular edema (DME) in patients with type 2 diabetes.Methods:A cross-sectional study was conducted.A total of 135 patients with type 2 diabetes, aged 45-75 years, who were treated in Gansu Provincial Hospital from April 2021 to April 2022 were included.According to DR grading standard, patients were divided into non-DR (NDR) group, non-proliferative DR (NPDR) group and proliferative DR (PDR) group, with 45 patients in each group.The DR patients were subdivided into DME group (51 cases) and non-DME group (39 cases).A total of 45 healthy subjects were selected as the normal control group.Fasting peripheral venous blood was collected to detect serum glycosylated hemoglobin, fasting blood glucose, triacylglycerol, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, CysC and CTRP9 levels.The expression of CysC and CTRP9 levels among different groups were compared.The independent influencing factors of DR and DME were evaluated by multivariate logistic regression analysis model.The diagnostic value of serum CysC and CTRP9 in DR and DME were evaluated by receiver operating characteristic (ROC) curve.This study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Gansu Provincial Hospital (No.2021-301).All patients were informed about the purpose and methods of the study and signed an informed consent form.Results:Serum CysC levels in normal control group, NDR group, NPDR group and PDR group were 0.74(0.67, 0.83), 1.03(0.85, 1.22), 1.40(0.98, 1.63) and 1.66(1.31, 1.85)mg/L, respectively, showing a gradually increasing trend, and the serum CTRP9 levels were (136.90±14.95), (120.23±16.31), (109.50±14.71) and (90.99±13.88)pg/ml, respectively, showing a gradually decreasing trend, with statistically significant overall comparison differences among groups ( Z=89.430, P<0.001; F=74.242, P<0.001), the comparison within groups was statistically significant (all at P<0.05).Compared with non-DME group, the serum CysC level was significantly increased and serum CTRP9 level was significantly decreased in DME group (both P<0.05).Multivariate logistic regression analysis showed that serum CysC (odds ratio [ OR]=19.742, 95% confidence interval [ CI]: 4.515-86.316, P<0.001) was the independent risk influencing factors for the occurrence of DR, and CTRP9 ( OR=0.937, 95% CI: 0.908-0.966, P<0.001) was a protective factor for the occurrence of DR.Serum CTRP9 level ( OR=0.838, 95% CI: 0.778-0.903, P<0.001) was a protective factor for DME.The ROC curve showed that the area under ROC curve (AUC) for serum CysC and CTRP9 levels alone and in combination for the diagnosis of DR in patients with type 2 diabetes mellitus complicated by DR were 0.798, 0.802 and 0.870, respectively.The cutoff values of serum CysC and CTRP9 levels to obtain the best diagnostic efficacy were 1.34 mg/L and 110.12 pg/ml, respectively.The AUC for serum CysC and CTRP9 level alone and in combination for the diagnosis of DME in DR patients were 0.682, 0.923 and 0.923, respectively.The cutoff value of serum CTRP9 level to obtain optimal diagnostic efficacy was 104.68 pg/ml. Conclusions:The enhanced expression of serum CysC level and reduced expression of serum CTRP9 level are the risk factors for the development of DR in type 2 diabetes patients.The decrease of serum CTRP9 level is one of the risk factors for the development of DME in DR patients.

ObjectiveAcute myocardial infarction (AMI) is a highly prevalent and deadly disease globally, with its incidence continuing to rise in recent years. Timely reperfusion therapy is crucial for improving the prognosis of AMI patients. However, myocardial reperfusion can lead to irreversible myocardial ischemia/reperfusion (MI/R) injury, which is associated with adverse cardiovascular outcomes following AMI. Studies have shown that microRNAs (miRNAs) are abnormally expressed during MI/R injury and play an important role in the fate of cardiomyocytes. Effective preventive and therapeutic strategies against MI/R injury remain lacking in clinical practice, necessitating elucidation of the molecular mechanisms underlying MI/R onset and progression. This study investigated the role of microRNA-878 (miR-878) in the regulation of mitochondria-mediated apoptosis in MI/R injury. MethodsThe H9c2 cells were flushed with a gas mixture containing 1% O₂, 5% CO₂ and 94% N₂ for 3 h. Then the cells were incubated in complete culture medium under 5% CO₂ and 95% air for 6 h to mimic in vivo hypoxia/reoxygenation (H/R) injury. Cell viability were detected by CCK-8 assay. The concentrations of lactate dehydrogenase (LDH) were then measured.The level of apoptosis was analyzed by flow cytometry. The morphology of mitochondria was analyzed by immunofluorescence and laser confocal microscopy. The levels of mitochondrial reactive oxygen species (mtROS) were detected by immunofluorescence. Dual luciferase reporter gene assay was used to study the binding site of miR-878 and Pim1. RNA immunoprecipitation (RIP) assay was used to verify the binding relationship between miR-878 and Pim1. The gene expression levels were detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blot. ResultsThe study found that compared with the control group, the expression of miR-878 in H/R-treated H9c2 cells was significantly increased ((1.00±0.25) vs (9.70±2.63), P<0.01). In H/R-induced cells, transfection of miR-878 inhibitor significantly increased cell viability ((46.67±3.00) vs (74.62±4.08), P<0.000 1), and decreased LDH release ((358.58±41.71) vs (179.09±15.59), P<0.000 1) and cell apoptosis rate ((43.41±0.72) vs (27.42±4.48), P<0.01). At the same time, downregulation of miR-878 expression significantly inhibited DRP1-mediated mitochondrial overdivision and mtROS production ((6.60±0.57) vs (4.32±0.91), P<0.000 1). The mechanism study showed that miR-878 could target and bind Pim1 and inhibit the expression level of Pim1 ((1.00±0.13) vs (0.38±0.03), P<0.01). Rescue experiments confirmed that down-regulation of Pim1 expression significantly reversed the anti-injury effect of miR-878 inhibitor in H9c2 cells (P<0.01), promoted mitochondrial overdivision and mtROS production ((1.00±0.12) vs (2.41±0.12), P<0.01), and decreased the expression level of p-DRP1 ((1.00±0.15) vs (0.59±0.06), P<0.05). ConclusionThe present study demonstrates that miR-878 expression is upregulated in H9c2 cardiomyocytes subjected to H/R injury. Inhibition of miR-878 expression alleviates H/R-induced cardiomyocyte damage. Notably, downregulation of miR-878 significantly inhibits DRP1-mediated mitochondrial fission and mitigates mtROS production. Mechanistically, miR-878 targets and binds to the 3'-UTR of the Pim1 gene, thereby suppressing Pim1 protein expression. Collectively, these findings suggest that under H/R conditions, miR-878 promotes excessive mitochondrial fragmentation through DRP1 activation by targeting Pim1, ultimately contributing to cardiomyocyte injury. Modulation of the miR-878/Pim1 axis may represent a potential therapeutic strategy for mitigating MI/R-induced cardiac damage.

Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

The rare-earth-elements-doped upconversion nanoparticles NaYF4:Yb3+,Er3+were synthesized by solvothermal method,and NaYF4:Yb3+,Er3+@SiO2 were prepared by coating SiO2 on the surface of NaYF4:Yb3+,Er3+by inverse microemulsion method in this work.Based on the fluorescence quenching principle between NaYF4∶Yb3+,Er3+@SiO2 and SQA-Fe3+,a NaYF4∶Yb3+,Er3+@SiO2-SQA-Fe3+fluorescence nanosensor was constructed for detection of trace hydrogen peroxide(H2O2).Under optimal conditions,the linear range of this method for detecting H2O2 was 1.8?84.0 μmol/L,with detection limit(3σ)of 0.47 μmol/L.The recoveries of H2O2 spiked in milk were 98.4%?99.7%.This method could be used for detection of H2O2 residue in milk samples,with advantages such as low detection limit,good stability and strong anti-interference ability.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To explore the correlation between sleep status and traditional Chinese medicine(TCM)constitution types of sub-healthy population in Lingnan area.Methods From May 2022 to May 2023,an investigation was carried out in a sub-healthy population of 688 persons who lived in Shenzhen for more than 5 years,had no serious cardiovascular disease and were confirmed by the sub-health rating scale.The questionnaire survey of Pittsburgh Sleep Quality Index(PSQI)scale and the TCM constitution classification rating scale was conducted,and multiple linear regression analysis was performed to explore the correlation between the sleep status and TCM constitution types.Results(1)A total of 688 questionnaires were released,of which 19 were lost to follow-up,and 669 were responded.After weeding out the 29 invalid questionnaires,640 valid questionnaires were finally included for the analysis.(2)According to the PSQI score,the population was divided into excellent sleep group(total PSQI score＜8)of 350 cases and poor sleep group(total PSQI score≥8)of 290 cases.The item scores of time for falling asleep,sleep time and sleep disorder as well as the total PSQI score of the excellent sleep group were significantly lower than those of the poor sleep group(P＜0.05 or P＜0.01).(3)The persons with excellent sleep usually had the balanced constitution(86.86%),while the persons with poor sleep often had the biased constitution(79.64%).The top three biased constitution types in the persons with poor sleep were damp-heat constitution(15.52%),phlegm-damp constitution(13.79%)and qi-stagnation constitution(13.10%).(4)Multiple linear regression analysis showed that the time for falling asleep was positively correlated with phlegm-damp constitution and qi-stagnation constitution(P＜0.01),and was negatively correlated with balanced constitution(P＜0.05);the sleep efficiency was positively correlated with damp-heat constitution and inherited special constitution(P＜0.05 or P＜0.01),and was negatively correlated with balanced constitution(P＜0.05);sleep disorder was positively correlated with qi-stagnation constitution and yin-deficiency constitution(P＜0.01);hypnotic drugs were positively correlated with yin-deficiency constitution(P＜0.01);daytime dysfunction was positively correlated with phlegm-damp constitution(P＜0.05).Conclusion The sleep status of sub-healthy population in Lingnan area has a certain correlation with TCM constitution types.Damp-heat constitution,phlegm-damp constitution,qi-stagnation constitution,yin-deficiency constitution,balanced constitution and inherited special constitution are the six constitution types that affect sleep status.It is of great significance to guide the sub-healthy population to achieve the purpose of prevention before illness by improving their constitution after the identification of TCM constitution types.

Objective To investigate the effect of Xiao Chaihu Decoction and Xiangsha Liujunzi Decoction on the changes of gastric mucosal pathological score and gastrointestinal hormones in patients with chronic atrophic gastritis(CAG)of liver stagnation and spleen deficiency type.Methods A total of 156 cases of CAG patients with liver stagnation and spleen deficiency syndrome were randomly divided into a control group and an observation group,78 cases in each group.The control group was treated with conventional western medicine,and the observation group was treated with Xiao Chaihu Decoction and Xiangsha Liujunzi Decoction on the basis of treatment for the control group.The course of treatment covered four weeks.The changes in the scores of traditional Chinese medicine(TCM)symptoms such as epigastric distention and pain,poor appetite,loose stools,limb weakness,belching and acid regurgitation,gastric mucosal pathological scores and serum levels of gastrointestinal hormones of motilin(MTL)and gastrin(GAS)in the two groups were observed before and after treatment.The negative conversion rate of Helicobacter pylori(Hp)in the two groups was compared,and the clinical efficacy and safety of the two groups were evaluated.Results(1)After four weeks of treatment,the total effective rate of the observation group was 93.59％(73/78),which was significantly higher than 82.05％(64/78)of the control group,and the difference between the two groups was statistically significant(P＜0.05).(2)After treatment,the scores of TCM symptoms such as epigastric distention and pain,poor appetite,loose stool,limb weakness,belching and acid regurgitation in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the pathological scores of gastric mucosa in the two groups were significantly decreased when compared with those before treatment(P＜0.05),and the decrease in the observation group was more significant than that in the control group(P＜0.01).(4)After four weeks of treatment,the negative conversion rate of Hp in the observation group was 91.03％(71/78),which was significantly higher than that in the control group(75.64％,59/78),and the difference between the two groups was statistically significant(P＜0.05).(5)After treatment,the level of serum GAS in the two groups was significantly decreased(P＜0.05)and the serum MTL level was significantly increased compared with that before treatment(P＜0.05);the decrease of serum GAS level and the increase of serum MTL level in the observation group were significantly superior to those in the control group(P＜0.05).(6)There were no obvious abnormalities in the routine test of blood,urine,stool,kidney function,and liver function,electrocardiograph and other safety indicators during the treatment of the two groups of patients,no adverse reactions such as dizziness,rash and chest distress occurred either,with high safety.Conclusion Xiao Chaihu Decoction combined with Xiangsha Liujunzi Decoction exerts a significant therapeutic effect on GAS of liver stagnation and spleen deficiency type,which can effectively relieve the clinical symptoms,improve the pathological changes of gastric mucosa and promote Hp negative conversion.The therapeutic mechanism may be related to the regulation of gastrointestinal hormone levels.

Objective To measure the distance between the lateral compression Ⅱ(LC-Ⅱ)screw guide needle and the surrounding important structures around the anterior inferior iliac spine in pelvic fractures and to locate the needle point,so as to provide anatomical reference for clinical nail placement.Methods Totally 40 adult gross specimens of embalming were implanted with LC-Ⅱ screw guide needle under the surveillance of C-arm machine,and the specimens were dissected.The shortest distance between the insertion point and the lateral femoral cutaneous nerve,femoral nerve,femoral artery,femoral vein,anterior superior iliac spine and inguinal ligament was measured.The triangle was constructed between the insertion point,anterior superior iliac spine and inguinal ligament,and the exact location of the entry point was calculated.Results The average distance between the insertion point of the male needle and the femoral vein was(50.67±7.29)mm＞the anterior superior iliac spine(43.83±7.58)mm＞the femoral artery(38.35±6.63)mm＞the femoral nerve(31.17±1.67)mm=the inguinal ligament(28.69±6.59)mm＞the lateral femoral cutaneous nerve(7.98±3.81)mm.The mean distance between the insertion point of the female needle and the anterior superior iliac spine was(45.28±7.07)mm=femoral vein(43.72±6.89)mm＞femoral artery(33.76±6.33)mm＞femoral nerve(25.66±6.46)mm=inguinal ligament(23.22±5.00)mm＞lateral femoral cutaneous nerve(8.97±4.76)mm.The projection distance of the entry point was 31.77 mm for men and 38.41 mm for women.The Angle b was 42.81°for men and 31.71° for women.Conclusion The lateral femoral cutaneous nerve is most vulnerable to injury when LC-Ⅱ screw is inserted,and the risk of injury has nothing to do with sex.The insertion point positioning method a and b made LC-Ⅱ screw placement quickly,safely and accurately,and reduced fluoroscopy time and frequency.

Active immunotherapy for cancer aims to treat disease by inducing effective cellular immunity and humoral immunity.Research on virus-like particles(VLPs)vaccines has made tremendous progress in recent years,dramatically reducing morbidity and mortality from some infectious diseases.VLPs are nanoparticles self-assembled from one or more structural proteins,with highly ordered repeat sequences and good immunogenicity,which can induce strong cellular immune and humoral immune responses.VLPs can overcome immunosuppressive state of tumor microenvironment,break self-tolerance,and trigger strong cytotoxic T lymphocyte activity,which is critical for both viral clearance and destruction of cancer cells.This article mainly reviews current research progress of VLPs-based cancer vaccines and potential defects of VLPs as vaccine carriers in development of cancer vaccines.