Lipocalin-2 (LCN2), a member of the human lipocalin family, has been demonstrated to be closely associated with diabetes, cardiovascular diseases, and renal disorders. Recent studies have indicated that LCN2 plays a significant regulatory role in the pathogenesis and progression of various neurological diseases by mediating pathways such as inflammation, oxidative stress, and ferroptosis. This article reviews the research advancements on the mechanism of LCN2 in neurological disorders, including cerebrovascular diseases, cognitive impairment disorders, Parkinson's disease, depression, and anxiety disorders, aiming to enhance clinical understanding.

Background::Psychological stress has been reported to be a potential risk factor for hypertension among females, but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among women. We examined the associations between stress within the family and hypertension among married women.Methods::Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects (NFPCP) across 31 provinces in China in 2016 and 2017. Perceived stress of wives or husbands was measured with a 5-point Likert-type scale, and assessed from three domains: work/life-related stress, economic stress, and overall stress. Multivariable-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of hypertension.Results::Of 10,027,644 couples, 261,098 (2.60%) women had hypertension. The results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women ( Pfor trend <0.001). Compared with non-stressed participants, female participants with the highest stress themselves were at a greater risk of hypertension, with adjusted odds ratio (OR) of 1.31 (95% confidence interval [CI]: 1.25-1.37); and compared with participants whose husbands had no stress, those whose husbands had the highest stress level were at a higher risk of hypertension with adjusted OR of 1.24 (95% CI: 1.20-1.29). Moreover, compared with non-stressed status for both couples, only-wife-stressed, only-husband-stressed, and both-stressed couples were found to be significantly associated with increased risks of wives’ hypertension, with adjusted ORs of 1.28 (95% CI: 1.25-1.31), 1.19 (95% CI: 1.17-1.21), and 1.28 (95% CI: 1.26-1.31), respectively. Conclusion::Moderate to severe stress in both spouses might be associated with female hypertension prevalence, which highlights the importance of paying attention to the psychological stresses of couples within the family.

Objective To assess the causality between 14 malignant tumors and hypertension.Methods Publicly available datasets from genome-wide association study were used,from which independent genetic variants strongly associated with hypertension and 14 malignant tumors were extracted as instrumental variables for bidirectional Mendelian randomization(MR)analysis,including random effect inverse variance weighted(IVW),simple mode,weighted median,weighted mode and MR-Egger to evaluate the causal effect.Sensitivity analysis was used to test the validity and robustness of the analytical results,and multivariate MR method was used to further control for the effects of confounding factors.Results In the MR analysis of malignant melanoma and hypertension,the study included a total of 11 single nucleotide polymorphisms(SNPs)strongly associated with malignant melanoma.After Bonferroni correction,the IVW-based results showed a causal relationship between malignant melanoma and hypertension(OR=1.67,95％CI:1.27-2.21,P＜0.001).Cochran's Q test,Mendelian randomization pleiotropy residual sum and outlier test and MR-Egger intercept test showed that there were no outliers and no horizontal pleiotropy among the instrumental variables,and the sensitivity analysis of the leave-one-out method showed that there was no single SNP that had a significant impact on the overall results.In the analysis of hypertension and leukemia,the preliminary analysis results showed that there may be a relationship between the two,but after adjusting for confounders,the effect of hypertension on the risk of leukemia was no longer significant.Conclusion Malignant melanoma may be a risk factor in the development of hypertension.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

It is believed that retention due to deficient qi is an important pathogenesis of endometriosis （EMs）. Deficient qi is the root of the disease， mainly manifested as spleen deficiency， while retention is the branch pathogenesis of the disease， mainly with blood stasis， complicated with constraint， phlegm， heat， toxin and other pathological factors. Therefore， it is proposed to follow the treatment principle of supplementing deficiency and unblocking stagnation， and take the methods of replenishing qi and fortifying the spleen， removing stasis and eliminating concretions. Self-made Fuzheng Huayu Formula （扶正化瘀方） is taken as the basic formula， and can be modified with the symptoms in menstrual and non-menstrual periods. Additionally， the methods of moving qi， dispelling phlegm， clearing heat， relieving toxin and others can be combined， and it is recommended to treat the root and the branch simultaneously.

Alzheimer's disease(AD), the most common neurodegenerative disease, has shown an increasing incidence among younger people. With the onset of disease, most patients' cognitive function will show a progressive decline, bringing a heavy burden to the society and the family. Studies have shown that fibroblast growth factor (FGF) may be involved in the pathogenesis of AD through multiple mechanisms. This article reviews the mechanism of FGF in AD, with the hope of providing new ideas for elucidating the pathogenesis and early diagnosis of AD.

Background Arsenic can be toxic to human by triggering oxidative stress, which is companied by epigenetic modifications. Objective To investigate the modification of N⁶-methyladenosine (m⁶A) in human embryonic lung fibroblasts (HELF) during oxidative stress induced by sodium arsenite (NaAsO₂). Methods HELF cells were treated by designed concentrations of NaAsO₂ (0, 2.5, 5, 10, and 20 μmol·L⁻¹) for 48 h. Cell viability was detected by 3-(4,5-dimethylthia zol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium (MTS) method; the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) as well as the content of malondialdehyde (MDA) were detected with corresponding kits; the level of m⁶A methylation in total RNA was detected by enzyme-linked immunosorbent assay; the mRNA expressions of m⁶A modified enzymes were detected by real-time fluorescence quantitative PCR, including methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), Wilms' tumor 1-associated protein (WTAP), fat mass and obesity-associated protein (FTO), alkB family of Fe(II)/α-ketoglutarate-dependent dioxygenases 5 (ALKBH5), YTH domain containing protein 2 (YTHDC2), YTH domain family protein 2 (YTHDF2), and YTH domain family protein 3 (YTHDF3); the protein expressions of METTL3, FTO, YTHDC2, YTHDF3, and nuclear factor erythroid 2-related factor 2 (NRF2) were detected by Western blotting. The enrichment of m⁶A in NRF2 mRNA was detected by RNA methylated immunoprecipitation combined with real-time fluorescence quantitative PCR (MeRIP-qPCR). Results After the 0, 2.5, 5, 10, and 20 μmol·L⁻¹ NaAsO₂ treatment, the MTS results showed that compared with the control group, the cell viability of the 20 μmol·L⁻¹ group decreased to 84% (P<0.05). The colorimetry results showed that compared with the control group, the activities of T-SOD in the 10 and 20 μmol·L⁻¹ groups decreased (P<0.05); the activities of GSH-Px in the 2.5 and 10 μmol·L⁻¹ groups decreased (P<0.05); the contents of MDA in the 10 and 20 μmol·L⁻¹ groups increased. The results of enzyme-linked immunosorbent assay showed that the overall m⁶A methylation levels in the 0, 2.5, 5, 10, and 20 μmol·L⁻¹ groups were (0.193 ± 0.023)%, (0.247 ± 0.021)%, (0.253 ± 0.006)%, (0.233 ± 0.006)%, and (0.262 ± 0.010)%, respectively, and compared with the control group, the m⁶A methylation levels in all the NaAsO₂ treated groups increased (P<0.05). The real-time fluorescence quantitative PCR results showed that compared with the control group, the mRNA relative expression level of METTL3 decreased in the 2.5, 10, and 20 μmol·L⁻¹ groups (P<0.05); the mRNA relative expression level of FTO decreased in the 20 μmol·L⁻¹ group; the mRNA relative expression level of YTHDC2 increased in the 10 and 20 μmol·L⁻¹ groups (P<0.05); the mRNA relative expression level of YTHDF3 increased in the 2.5, 10, and 20 μmol·L⁻¹ groups (P<0.05). The Western blotting results showed that compared with the control group, the relative protein expression of METTL3 decreased in the 10 and 20 μmol·L⁻¹ groups; the relative protein expression of FTO decreased in the 5 and 20 μmol·L⁻¹ groups; the relative protein expression of YTHDC2 decreased in the 20 μmol·L⁻¹ group (P<0.05); the relative nuclear protein expression of NRF2 decreased in the 10 and 20 μmol·L⁻¹ groups (P<0.05). The MeRIP-qPCR results showed that m⁶A enrichment was significantly increased in the 20 μmol·L⁻¹ NaAsO₂ exposure group compared with the control group (P<0.05). After over-expression of FTO, the mRNA and protein relative expression levels of FTO and the relative expression level of nuclear protein of NRF2 in the FTO group were higher than those in the control group (P<0.05); the mRNA and protein relative expression levels of FTO in the NaAsO₂ + FTO group and the nuclear protein expression level of NRF2 were higher than those in the NaAsO₂ group (P<0.05). Conclusion In the process of oxidative stress induced by NaAsO₂, m⁶A methylation level, m⁶A modified enzymes, m⁶A modification of NRF2 mRNA, and NRF2 expression could change in HELF cells.

Objective:The clinical features, laboratory indices, and imaging data of patients with Pneumocystis jirovecii pneumonia (PJP) were described and analyzed, aiming to provide helpful information for the diagnosis and treatment of PJP. Methods:A retrospective study were conducted with data from 154 PJP patients who visited China-Japan Friendship Hospital from May 2017 to August 2020. Their clinical characteristics, laboratory and imaging data, and clinical outcomes were collected for analysis. The patients were further divided into the death group (51 cases) and the survival group(103 cases). The differences between the groups were compared by using t-test, nonparametric test, and chi-square test. Results:Of the 154 PJP patients, there were 89 males and 65 females, with a mean age of (53.7±14.8) years. Among them, 85.7% (132/154) were on immunosuppressive/glucocorticoids agents within the past month. Besides, 27.9% (43/154) and 33.1% (51/154) had kidney diseases and connective tissue diseases, respectively. The major clinical manifestations in these patients involved fever 82.9% (126/154), cough 59.7% (92/154), and dyspnea 52.6% (81/154). For the laboratory data, the lactate dehydrogenase (LDH) was 561.0 (434.3, 749.0) IU/L and the value increased in 91.3% (95/104) of the patients. The CD4+T-cell lymphocytes in 88.0% (95/108) and 57.4% (62/108) of patients were lower than 400/μl and 200/μl, respectively. Furthermore, (1, 3)-β-D glucan (BG) increased in 74.4% (67/90) of PJP patients (≥100.0 ng/L). For the imaging results, chest computed tomography (CT) showed diffuse ground-glass shadows/grid shadows in 90% (117/130) patients. Compared with the survival group, higher LDH [690.5 (528.8, 932.3) IU/L vs 502.5 (381.8, 657.0) IU/L, Z=-3.375, P=0.001], white blood cell count (WBC) [9.8 (5.8, 12.6) ×10 9/L vs 7.3 (5.0, 10.1) ×10 9/L, Z=-2.392, P=0.017], and age [(69.8±14.5) years vs (50.6±14.0) years, t=-3.756, P=0.001] were found in the death group. Lower lymphocyte ratio [5.3 (3.2, 9.3) % vs 9.6 (5.6, 17.2) %, Z=?3.262, P=0.001] and oxygen partial pressure (PaO 2) levels [(73.2±20.5) mmHg vs (64.8±17.7) mmHg (1 mmHg=0.133 kPa), t=2.345, P=0.021] were also observed in the death group. Furthermore, in the death group, the bacterial and fungal infection rate was higher than the rates in the survival group [55.1% (27/51) vs 21.5% (22/103), χ 2=15.372, P=0.001]. Conclusions:Long-term use of immunosuppressive agents or glucocorticoids predispose to PJP. CD4+T-lymphocytes, LDH, and BG might be used as important auxiliary examinations for PJP patients. Age, LDH, WBC, lymphocyte ratio, PaO 2 and possible combinations with bacterial or fungal infections are more closely related to the prognostic of PJP patients.

Objective To establish the finite element model of upper cervical vertebrae C0-3 with Jefferson fracture, and to analyze the influence of posterior atlantoaxial fusion (PSF) and occipitocervical fusion (OCF) on biomechanical properties of the vertebral body and mechanical conduction of the screw-rod system. Methods Based on CT images, the C0-3 segment Jefferson fracture model of human upper cervical spine was established. PSF, OCF1 and OCF2 internal fixation were performed according to surgical plan in clinic, and 50 N concentrated force and 1.5 N·m torque were applied to bottom of the occipital bone. The stress distribution and range of motion (ROM) of the cervical vertebral body, the maximum stress of the screw-rod system and the stress distribution of the intervertebral disc for C0-3 segment during flexion, extension, bending and rotation of the upper cervical spine were studied. Results Compared with PSF, the ROM of OCF1 and OCF2 vertebral bodies increased, and the stress of the nail rod decreased. OCF had a better fixation effect. Conclusions PSF, OCF1 and OCF2 fixation method can reduce the upper cervical ROM and restore stability of the upper cervical spine, which make stress distributions of the vertebral body and intervertebral disc tend to be at normal level. The research result can provide a theoretical basis for clinical surgery plan.

Department of Orthopedics, Yang Pu Hospital Affiliated to Tongji University,