To establish a simple,convenient,sensitive,and specific method for rapid detection of Zi-ka virus(ZIKV),the whole genome sequences of ZIKV isolated from different times and regions were analyzed.The specific primers and probes were designed based on the screened target se-quences located in the conserved region of the ZIKV NS5 gene.By combining RT-LAMP isother-mal amplification technology and immunochromatography technology,a reverse transcription loop mediated isothermal amplification nucleic acid and flow visualization strip(RT-LAMP-VF)detec-tion method for ZIKV was established.The results showed that the method had good specificity and sensitivity.When the ratio of inner,outer,and ring primers(FIP∶LF∶F3)was 4∶2∶1,the detection method can specifically detect 102 copies/pL RNA transcripts or 2.15 pfu ZIKV at 61 ℃for 45 minutes,with no cross reaction with other flaviviruses such as Japanese encephalitis virus and classical swine fever virus.Other RNAs in blood tissue samples did not affect the sensitivity and specificity of RT-LAMP-VF,indicating that the method can be applied to clinical practice.The ZIKV RT-LAMP-VF detection method established in this study is easy to perform and does not require special instruments and equipment.It is particularly suitable for the rapid detection of ZIKV in grassroots units,providing technical support and material support for the establishment of on-site rapid detection and early warning and prediction systems for ZIKV disease.

Objective To observe the clinical effect of Tiaoshen Yangxin decoction on insomnia in perimenopausal patients with heart-kidney disharmony type.Methods From July 2022 to July 2023,60 patients with perimenopausal insomnia of heart-kidney disharmony type who met the diagnostic criteria were selected from Tongde Hospital of Zhejiang Province.The patients were divided into control group and experimental group by random number table method,30 cases in each group.The patients in control group were treated with Wuling capsule,and the patients in experimental group were treated with Tiaoshen Yangxin decoction.Before treatment and 8 weeks after treatment,the Pittsburgh sleep quality index (PSQI) score,Kupperman menopause index (KMI) score,Hamilton anxiety scale (HAMA) and TCM syndrome score were compared between two groups.Results After 8 weeks of treatment,the total effective rate of experimental group patients was 96.7％,which was higher than that of control group's 86.7％ (x2=17.153,P=0.000);The scores of the symptom of hot flashes,sweating,insomnia,palpitations,etc.in experimental group patients were lower than those in control group (P<0.05);The HAMA score and TCM syndrome score of experimental group patients after treatment were lower than those of control group (P<0.05).Conclusion The curative effect of Tiaoshen Yangxin decoction on insomnia in perimenopausal patients is better than that of Wuling capsule.In addition,Tiaoshen Yangxin decoction can also improve the symptoms of hot flashes,sweating,palpitations in perimenopausal insomnia patients and relieve anxiety.

OBJECTIVE To optimize the rivaroxaban dosing regimen for anticoagulation in patients with different renal function levels. METHODS The administration regimen was determined based on the drug instructions for rivaroxaban and the actual medication situation of the patient. The target concentration range and the subsection interval were established using rivaroxaban blood minimum concentration for patients from Hebei General Hospital and reference range of rivaroxaban laboratory monitoring concentration recommended by International Council for Standardization in Hematology. The probability of different dosing regimens in each target concentration range was investigated with Monte Carlo simulation using Oracle Crystal Ball software （V11.1.2.4）. RESULTS A total of 97 patients with non-valvular atrial fibrillation were enrolled and the minimum concentration of rivaroxaban was tested 125 times with a median trough concentration of 32.2 ng/mL； a total of 121 patients with venous thrombosis were enrolled and the minimum concentration was tested 159 times with a median minimum concentration of 31.0 ng/mL. The reference range for steady-state minimum concentration in patients with non-valvular atrial fibrillation was 12-137 and 3-153 ng/mL， while the reference range for steady-state minimum concentration in patients with venous thrombosis was 6-239 and 3-224 ng/mL. Monte Carlo simulation results showed that in patients with non-valvular atrial fibrillation， the optimal rivaroxaban dosing regimen for patients with glomerular filtration rate （eGFR） 0-30 mL/min was 5 mg once daily； for patients with eGFR＞30-60 mL/min， the optimal dosing regimen was 10-20 mg once daily or 5 mg twice daily； for patients with eGFR＞60-90 mL/min， the optimal dosing regimen was 15-30 mg once daily or 5-10 mg twice daily； for patients with eGFR＞90-120 mL/min， the optimal dosing regimen was 25-30 mg once daily or 5-15 mg twice daily. For patients with venous thrombosis， it is not recommended to use rivaroxaban more than 5 mg once daily for patients with eGFR 0-30 mL/min； the optimal dosing regimens of rivaroxaban were 5 mg once daily for patients with eGFR＞30-60 mL/min， 25- 30 mg once daily or 5-15 mg twice daily for patients with eGFR＞60-90 mL/min， 10-15 mg twice daily for patients with eGFR＞ 90-120 mL/min. CONCLUSIONS Rivaroxaban should be selected carefully as the anticoagulants for patients with severe renal function impairment. Rivaroxaban possesses a wide reference range in the minimum concentration and considerable individual variability. The dosage and frequency of rivaroxaban can be personalized through the Monte Carlo simulation method， taking into account patients’ renal function.

The spectrum of biopsy-confirmed kidney disease varies with regions and periods. We describe the distribution of pathological types and epidemiological characteristics of kidney diseases in Northwest China due to regional differences in geographical environment, social economy, and dietary habits. Methods: Kidney biopsy cases from 2005 to 2020 in Xijing Hospital were retrospectively analyzed. Pathological characteristics of patients in different periods were analyzed using the t test or chi-square test. Joinpoint regression was used to analyze trends in pathological types and disease spectrum. Results: A total of 10,528 eligible patients were included. Primary glomerular disease (PGD) accounted for the majority of the cases and exhibited an obvious downward trend, whereas secondary glomerular disease (SGD) showed an obvious upward trend. Among PGD, immunoglobulin A nephropathy (IgAN) remained the most common pathological type, and the detection rate of membranous nephropathy (MN) was significantly increased. Among SGD, Henoch-Schönlein purpura nephritis (HSPN) was the most common pathological type and may present a significant characteristic of Northwest China. Diabetic nephropathy (DN) exhibited the most obvious upward trend in the whole process, whereas the fastest growth since 2012 was in hypertensive nephropathy. Conclusion: The proportion of SGD increased whereas PGD declined. IgAN remained the most common PGD, and HSPN was the most common SGD. MN and DN showed the most obvious upward trend among PGD and SGD, respectively. Changes in the spectrum of kidney disease, especially the constituent ratio of SGD, pose a great challenge to public health.

Objective To observe the value of 18F-FDG PET/CT combined with tumor markers for diagnosis of non stageⅠ A limited-stage small cell lung cancer(LS-SCLC).Methods Totally 87 cases of non stage Ⅰ A LS-SCLC(LS-SCLC group),137 of non stage Ⅰ A non-small cell lung cancer(NSCLC,NSCLC group)and 48 cases of pulmonary inflammatory lesions(inflammatory group)were enrolled.Patients'general data,tumor marker levels and PET/CT findings were comparatively analyzed.Logistic regression analysis was performed to evaluate the efficacy of parameters for diagnosing non stage Ⅰ A LS-SCLC.Results There were significant differences of patients'age,neuron-specific enolase(NSE),pro-gastrin-releasing peptide(ProGRP),carcinoembryonic antigen(CEA),squamous cell carcinoma antigen(SCCA)and cytokeratin-19-fragment(CYFRA21-1),as well as of the maximum lesion diameter,maximum standard uptake value(SUVmax),morphology,spiculation sign,relationship between long axis and bronchus,lymph node fusion and proportion of lymph node with higher SUVmax than primary lesion among 3 groups(all P＜0.05).The area under the curve(AUC)of the combination of spiculation sign,NSE＞23.5 μg/L,ProGRP＞111.8 ng/L,SCCA≤2.5 μg/L and CYFRA21-1≤7.4 μg/L for differentiating LS-SCLC and NSCLC was 0.91,higher than that of each single parameter(all P＜0.05).AUC of the combination of SUVmax＞8.1,NSE＞19.4 μg/L,ProGRP＞72.5 ng/L and lymph node fusion for differentiating LS-SCLC and pulmonary inflammatory lesions was 0.99,higher than each single parameter(all P＜0.05).Conclusion 18F-FDG PET/CT combined with tumor markers ProGRP and NSE was helpful for diagnosing non stage ⅠA LS-SCLC.

Objective:To analyze the impact of global budget on the medical flow treatment and fund allocation in a non-compact medical community based on the symbiosis theory, so as to provide references for relevant authorities to formulate policies for the medical community.Methods:Data on outpatient and emergency visits, discharges, and medical insurance fund usage of the leading hospital and primary medical and health institutions in a non-compact medical community were collected from the health information system of a certain city. The time range of the data spanned from January 2017 to December 2019. The total budget was implemented in April 2018. The symbiotic system of the non-compact medical community was analyzed based on the theory of symbiosis. Descriptive analysis and intermittent time series segmented regression model were used to analyze the changes in indexes related to the flow of medical treatment and fund allocation between the leading hospital and primary institutions under the global budget.Results:The non-compact medical community′s symbiotic system had developed a continuous symbiotic model in organization and an asymmetric reciprocal symbiotic model in behavior. From the perspective of medical treatment flow, the number of outpatient and emergency visits of leading hospital and primary institutions in the medical community showed an upward trend, with little change in the number of discharged patients from 2017 to 2019; The number of patients transferred by the leading hospital increased from 32 in 2017 to 87 in 2019. According to the analysis of the intermittent time series segmented regression model, after the implementation of global budget, the proportion of outpatient and emergency visits in leading hospital was decreased ( β3=-0.43, P<0.05), the proportion of outpatient and emergency visits in primary institutions was on the rise ( β3= 0.02, P<0.05). In terms of fund allocation, the share of health insurance fund of the leading hospital increased from 45.98% in 2017 to 46.51% in 2019, and the primary medical and health institutions decreased from 23.44% to 18.06%, as well as the ratio of per capita income of primary medical and health institutions to that of leading hospitals was decreased from 72.62% to 60.79%. Conclusions:Under the global budget, the outpatient and emergency medical treatment flow in a non-compact medical community had been optimized. However, there was an uneven distribution of funds among medical institutions at all levels. Thus it was recommended to continue to give full play to the positive incentive effect of the global budget, establish a scientific mechanism for distributing benefits, and strengthen supervision and management.

OBJECTIVES: Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment. METHODS: Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (e_i) and degree (k_i). RESULTS: Repeated measures 2-factor ANCOVA showed significant main effects on group on the e_i and k_i values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the e_i and k_i values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher e_i and k_i values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher e_i and k_i values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher e_i and k_i values of LSFG (P=0.019 and P=0.026, respectively), and higher e_i value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher e_i values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the e_i and k_i values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the k_i value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment. CONCLUSIONS There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high e_i of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased e_i and k_i values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.
Anhedonia ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; Prefrontal Cortex

Ferroptosis is a new type of programmed cell death that is closely associated with the pathophysiological process of ischemic stroke. Ferroptosis inhibitors can improve neurological function and provide neuroprotection after cerebral ischemia. Therefore, the role of ferroptosis in ischemic stroke and the regulation of ferroptosis to intervene in the occurrence and development of ischemic stroke have become a research hotspot. This article reviews the molecular mechanism and potential therapeutic targets of ferroptosis during ischemic stroke, hoping to provide new perspectives for the treatment of ischemic stroke.

Objective:To investigate the changes of blood pressure and serum circadian clock protein levels after cerebral ischemia-reperfusion in spontaneously hypertensive rat (SHR) and their correlation.Methods:The middle cerebral artery occlusion method was used to prepare the SHR cerebral ischemia-reperfusion model at zero point of Zeitgeber Time (ZT), and the systolic blood pressure within 24 h was continuously monitored after the model was made. The tail vein blood of rats was taken every 3 h, and the changes in serum circadian clock proteins (CLOCK, BMAL1, PER1 and CRY1) levels were detected by enzyme-linked immunosorbent assay. Pearson correlation analysis was used to determine the relationship between blood pressure circadian rhythm pattern and circadian clock protein level fluctuation after cerebral ischemia-reperfusion.Results:In the sham operation group, there were various blood pressure patterns, including dipper (53%), non-dipper (27%), super dipper (13%), and reverse dipper (7%), and the main pattern was dipper. In contrast, the degree of blood pressure disorder in the model group was aggravated, and the non-dipper was the main type, with the proportion as high as 40%. The proportion of super dipper and reverse dipper increased to 27% and 13% respectively; proportion of dipper blood pressure decreased to 20%. The serum level of CLOCK in the model group was relatively stable, while the circadian rhythm of BMAL1, PER1 and CRY1 was significantly changed compared with the sham operation group. Pearson analysis showed that PER1 was negatively correlated with the dipper ( r=-0.565, P=0.002) and super dipper ( r=-0.531, P=0.001) blood pressure patterns, and positively correlated with the non-dipper blood pressure pattern ( r=0.620, P<0.001). Conclusion:The circadian rhythm pattern of blood pressure in SHR after cerebral ischemia-reperfusion was obviously disordered, which was closely associated with the regulation of Per1 gene.

Rhythm of blood pressure refers to the circadian variation of blood pressure, which is regulated by clock genes. However, the rhythm disorder of blood pressure increases the risk of stroke. Taking the process of blood pressure regulation as a clue and focusing on the clock gene pathway, this article explores the possible mechanism of period gene regulating renin-angiotensin-aldosterone system in rhythm of blood pressure, so as to provide reference for the in-depth study of the relevant mechanism of rhythm disorder of blood pressure and search for a new target for the primary prevention of cerebrovascular diseases.