Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.

Objective To establish an HPLC method for the simultaneous determination of 10 components in the active parts of Uygur medicine Dracocephalum Moldavica L.Methods The determination was performed on a Shim-pack ODS(4.6 mm×250 mm,5 um)column with the mobile phase consisting of acetonitrile(A)-0.5%formic acid(B)in aqueous solution in a gradient elution mode(0-30 min,17%A;30-60 min,17%→ 28%A;60-78 min,28%A)at a flow rate of 1.0 mL·min-1.The temperature of the chromatographic column was 35℃and the detection was monitored by a UV detector at 330 nm.Results Cof-feic acid,p-coumalic acid,cynaroside,luteolin-7-O-β-D-glucuronide,apigenin 7-O-glucuronide,rosmarinic acid,diosmetin7-O-β-D-glucuronide,salvianolic acid A,tilianin,apigenin were well separated under this chromatographic condition,and the linear relation-ship were good in the concentration range examined(r＞0.999 2).The overall recoveries ranged from 91.83%to 106.43%with the RSD ranging from 0.38%to 2.22%.Conclusion The established content determination method is highly accurate and reproduci-ble,and suitable for the analysis and quality control of the active parts of Dracocephalum Moldavica L.

Objective:To explore the incidence of chronic obstructive pulmonary disease (COPD) in a cohort aged 40 years and above in Songjiang District, Shanghai, and to analyze the association of Mediterranean diet pattern and dietary approaches in stopping hypertension pattern (DASH) with the risk of developing COPD.Methods:Based on a natural population cohort in Songjiang District, Shanghai, 27 474 adults aged 40 years and above who did not have COPD at baseline were enrolled in the study. The Cox proportional risk regression model was used to analyze the association of baseline Mediterranean diet pattern score and DASH score with the risk of COPD, and the hazard ratio ( HR) of the risk and its 95% CI were calculated. Restricted cubic spline was used to analyze the nonlinear association between the two diet scores and the risk of COPD. Stratified analyses were performed according to gender, age, smoking status, etcetera. Sensitivity analyses were conducted by censoring cases diagnosed within one year after the baseline survey or people with a history of malignant tumor disease. Results:As of June 30, 2023, after a median follow-up time of 6.21 years, there were 1 089 (4.0%) new COPD cases with an incidence density of 64.00 per 10 000 person-years. After adjusting for relevant confounders, in the Mediterranean tertile subgroups under diet pattern score, the risk of developing COPD could be reduced by approximately 14% in the intermediate scoring group ( HR=0.86, 95% CI: 0.75-0.99) and 15% in the highest scoring group ( HR=0.85, 95% CI: 0.72-0.99) compared to the lowest scoring group. The association remained after censoring cases diagnosed within one year of the baseline survey ( HR=0.82, 95% CI: 0.70-0.95; HR=0.82, 95% CI: 0.68-0.97) or censoring people with a history of malignant tumor disease ( HR=0.84, 95% CI: 0.73-0.97; HR=0.84, 95% CI: 0.71-0.99). No statistical association was found between the DASH score and the risk of COPD. Conclusions:The Mediterranean diet pattern was associated with a lower risk of COPD. Increasing the intake of vegetables, fruits, legumes, and whole grains and decreasing the intake of red meat and others can reduce the risk of COPD. No association was found between the DASH dietary pattern and the risk of COPD in this community population.

Objective:To evaluate the cerebral infarct volume and the nerve fiber connectivity between cortical and neurogenesis-related regions in the mouse model of reperfusion after middle cerebral artery occlusion (MCAO) by 11.7 Tesla(11.7 T) magnetic resonance imaging (MRI).Methods:MCAO models were established in SPF grade adult male C57BL/6 mice using the suture-occluded method.MRI scans were performed at 3 days before and 1 day after modeling.Infarct volumes were calculated, and nerve fiber tracking was performed on specific brain regions to analyze the nerve fiber number and the parameters of fractional anisotropy(FA), mean diffusivity(MD), axial diffusivity (AD)and radial diffusivity(RD). SPSS 26.0 was used for statistical analysis, and paired t test was used to compare the data before and after modeling. Results:(1) After MCAO-induced ischemia, the infarct volume was up to (35.11±17.57)mm 3, and the FA value of the infarct area was significantly reduced compared with that of before modeling( t=4.73, P<0.01). (2) At the anterior-posterior(AP): + 1.2 mm section, the results of fiber tracking showed that compared with before modeling, the number of fiber bundles originating from the dorsal horn of the lateral sub-ventricle zone(SVZ)to the cortex reduced ((92 584.20±14 751.00) vs (59 815.60±6 752.46), t=4.87, P<0.01), and the number of fiber bundles projected to the infarcted area reduced ((107 671.40±10 497.57) vs (61 658.60±10 178.21), t=6.43, P<0.01). FA, AD, MD, and RD values were all decreased in different degrees( t=3.38-6.43, all P<0.05). (3) At the AP: -3.8 mm section, the number of fiber bundles originating from the dorsal horn of the SVZ to the cortex decreased (after modeling(96 944.00±18 331.09), before modeling(58 767.80±16 445.25), t=2.99, P<0.05), and the values of FA, AD, MD and RD decreased after ischemia ( t=7.30, 5.05, 6.74, 4.13, all P<0.05). Conclusion:The ultra-high field strength of 11.7 T MRI can accurately detect the following results that the number of nerve fiber bundles from the SVZ to the cortex or infarct area are both significantly reduced, and diffusion tensor parameters are consistently changed in mice after 1 day of ischemia-reperfusion.

Objective:To explore the application of microvascular flow imaging (MVFI) combined with high-frequency ultrasonography in children with haemophilic arthropathy A (HAA).Methods:Retrospective study.A total of 82 children diagnosed with HAA in the First Affiliated Hospital of Zhengzhou University from October 2018 to October 2020 were recruited.The elbow, knee and ankle joints of each child were examined by high-frequency ultrasonography.The numbers of thickened synovial joints were recorded.Blood flow signals of the thickening of synovial joints was checked by the MVFI and power Doppler ultrasound (PDUS), respectively.Color flow signals were graded by the semi-quantitative scoring systems.The chi- square test and independent multi-group ordinal multi-category rank-sum test were used to compare the differences of MVFI and PDUS in the display of thickened synovial blood flow. Results:A total of 254 joints were involved in 82 children with HAA, including synovial hypertrophy in 188 joints, hydrops articuli in 146 joints, fibrotic septa in 66 joints, cartilage damage in 63 joints, haemosider indeposition in 45 joints, bone erosion in 25 joints, osteophytes in 15 joints and bone remodeling in 8 joints.Grade Ⅱ synovial thickened joints were the most common.The proportion of blood flow signals detected by PDUS in thickened synovial membranes was significantly higher than that detected MVFI (52.66% vs.70.21%, χ2=12.225, P<0.05). Numbers of grade 0 and Ⅰ joints with thickened synovial membranes detected by MVFI were less than those of PDUS, while the opposite result was obtained in detecting grade Ⅱ and Ⅲ joints ( H=21.158, P<0.05). Compared with PDUS, MVFI more sensitively visualized the blood flow of the thickened synovial membrane. Conclusions:MVFI can more prominently detect the thickened synovial blood flow in children with HAA.A combined application of MVFI and high-frequency ultrasonography contributes to the evaluation of children with HAA.

The diagnosis of food allergy in children is one hotspot attracting people′s attention in recent years.The incidence of it shows an increasing trend which exposes problems in the understanding of children′s food allergy in China, especially in the misdiagnosis and missed diagnosis.To further standardize the diagnosis and treatment of food allergy in children, based on the current domestic, foreign guidelines and relevant research evidence, the guideline recommends 16 clinical hot-button issues in the 4 aspects of diagnosis, treatment, prognosis, and prevention.Finally, a diagnosis flowchart has been formulated.The guideline aims to improve the standard diagnosis and treatment of food allergies in children in China.

Background Dengue fever is a mosquito-borne disease transmitted by Aedes aegypti and Aedes albopictus. Under the background of climate change, there are great challenges in the prevention and control of dengue fever, posing a serious health risk to the population. Objective To analyze the mechanism of temperature on dengue fever transmission and estimate the risk of dengue fever under different climate change scenarios by establishing a coupled human-mosquito dynamics model using Guangzhou as a research site, and to provide reference for adaptation to climate change. Methods Reported dengue fever cases and meteorological data from January 1, 2015 to December 31, 2019 in Guangzhou were collected from Guangdong Provincial Center for Disease Control and Prevention and China Meteorological Data Service Centre, respectively. The temperature data under three Representative Concentration Pahtyway (RCP2.6, RCP4.5, and RCP8.5) scenarios in 2030s (2031–2040), 2060s (2061–2070), and 2090s (2091–2099) were calculated by five general circulation models (GCMs) provided by the fifth phase of the Coupled Model Intercomparison Project. A dengue fever transmission dynamics (ELPSEI-SEIR) model was constructed to analyze the mechanism of temperature affecting dengue fever transmission by fitting the dengue fever epidemic trend from 2015–2019, and then the daily mean temperature under selected RCP scenarios for 2030s, 2060s, and 2090s was incorporated into the established dynamics model to predict the risk of dengue fever under different climate change scenarios in the future. Results From January 1, 2015 to December 31, 2019, a total of 4 234 cases of dengue fever were reported in Guangzhou, including 3741 local cases and 493 imported cases. The regression results showed that the model well fitted the dengue fever cases in Guangzhou from 2015 to 2019, and the coefficient of determination R2 to evaluate goodness of fit and the root mean squared error were 0.82 and 1.96, respectively. A U-shaped or inverted U-shaped relationship between temperature and mosquito habits could directly affect the number of mosquitoes and the transmission of dengue fever. We also found that temperature increase in most future scenarios could promote the transmission of dengue fever, and the epidemic period was significantly wider than the baseline stage. The epidemic of dengue fever would peak in the 2060s under the scenarios of RCP2.6 and RCP4.5. The estimated incidence of dengue fever was predicated to be highest in the 2030s and then decrease in the following years under RCP8.5, and in the 2090s, the incidence would decrease significantly, but the incidence peak would be earlier in each year, mainly from May to July. Conclusion Temperature can directly affect mosquito population and dengue fever transmission by affecting mosquito habits. The cases of dengue fever will increase under most climate scenarios in the future. However, the epidemic risk of dengue fever may be suppressed, and the epidemic season may be advanced under RCP8.5.

Objective:To investigate changes in the bladder morphological structure and function and the expression of transforming growth factor-beta1 (TGF-β1) pathway-related proteins in the bilateral spinal nerve amputated neurogenic bladder(NB) rat.Methods:A total of 64 female SD rats were included, and 32 of them underwent bilateral spinal nerve L6+ S1 amputation to construct the NB model and the others were used as sham operation controls.Rats in both NB and control groups received bladder cystometry 3, 6, 12, 24 weeks after corresponding operation.Collagen fibers in their bladder tissues were detected by Masson staining and Sirius scarlet staining.TGF-β1, Smad2 and Smad6 proteins were checked by immunohistochemical staining.TGF-β1 receptor Ⅰ protein was measured by Western blot.Results:Bladders in the NB group were instable, with bladder leak point pressure(BLPP) and underactive voiding pressures.The basal pressure [(22.10±2.51), (18.20±1.52), (31.20±2.82), (41.10±3.41) cmH 2O(1 cmH 2O=0.098 kPa)] and bladder volume [(22.30±1.72), (49.10±5.54), (30.30±2.68), (13.50±1.52) mL] of the NB rats at 3, 6, 12 and 24 weeks were significantly higher than those of the sham operation controls[(3.51±0.45) cmH 2O and (0.52±0.04) mL], and the difference were significant(all P<0.05). The bladder size and thickness in the NB group firstly increased (3, 6 weeks) and then decreased (12, 24 weeks), but the bladder weight increased continuously.Masson staining showed disordered fibrous connective tissues, disintegrated layered bla-dder wall, hypertrophied smooth muscle tissues and deposited intramuscular collagen on the nerve-amputated bladder wall.Sirius scarlet staining suggested that 24 weeks after nerve amputation, collagen Ⅲ increased greatly, and the ratio of type Ⅲ/Ⅰ collagen fibers (3.14±0.71) was significantly higher than that in the sham group (0.88±0.21) ( t= 7.48, P<0.01). According to the immunohistochemical staining results, the expressions of TGF-1β and Smad2 increased while the pathway inhibitory protein Smad6 decreased with time in the NB group.Western blot showed that the expression of TGF-β1 receptor Ⅰ in the amputated bladder was 1.3 and 1.6 folds higher than that in the sham group 12 weeks and 24 weeks after operation( t=6.06, 14.45, all P<0.01). Conclusions:In NB rats with bilateral spinal nerve amputated, bladder contraction becomes paralysis, intravesical pressure increases, bladder normal structure disintegrates and the fibrosis pathway TGF-β1/Smads is activated.Therefore, the key step of development of pediatric NB is bladder fibrosis, which should be prevented as early as possibly in the clinical practice.

Objective:To investigate the urodynamic characteristics in Parkinson's disease(PD)versus multiple system atrophy(MSA)patients with lower urinary tract symptoms(LUTS).Methods:We performed a retrospective study in PD and MSA patients admitted to the First Affiliated Hospital of Zhengzhou University and undergone urodynamic examinations from January 2016 to June 2019.A total of 178 patients, mean age(59.2±9.7)years were enrolled, with 64 PD patients, 74 MSA patients and 40 normal controls.Urodynamic parameters included maximum flow rate(Qmax), post-voided residual urine volume(PVR), bladder compliance(BC), overactive bladder(OAB), maximum cystometric capacity(MCC)and detrusor pressure at maximum flow rate(PdetQmax). Bladder function was assessed.Results:Frequent urination(68.8%)was the most common LUTS in PD patients, as opposed to urinary retention(91.9%)in MSA patients.The Qmax, PdetQmax and incidence of OAB were higher and the PVR were lower in PD patients than in MSA patients [free-flow(FF)-Qmax: (13.5±7.1)ml/s vs.(10.1±5.2)ml/s, U=26.98, P<0.01]; pressure-flow study(PFS)-Qmax: [(13.6±5.7)ml/s vs.(10.5±3.3)ml/s, U=34.90, P<0.01]; PFS-PdetQmax: [(23.9±11.3)cm H 2O vs.(16.3±8.6)cmH 2O, U=35.04, P<0.01]; OAB: (46.9% vs.27.0%, χ2=5.85, P<0.01); FF-PVR: [(30.4±20.0)ml vs.(161.7±79.8)ml, U=-71.81, P<0.01]; PFS-PVR: [(65.9±30.7)ml vs.(212.6±83.0)ml, U=-65.29, P<0.01]. Compared with the control group, the incidences of OAB and PFS-PVR were increased and the MCC and PdetQmax were decreased in the PD group(OAB: 46.9% vs.7.5%, χ2=6.15, P<0.018); PFS-PVR: [(65.9±30.7)ml vs.(22.2±10.4)ml, U=47.25, P<0.01]; MCC: [(305.1±79.7)ml vs.(389.6±65.2)ml, U=-52.13, P<0.01]; PdetQmax: [(23.9±11.3)cmH 2O vs.(37.3±10.3)cmH 2O, U=-49.88, P<0.01]. Compared also with the control group, the MSA group had a lower Qmax, PdetQmax and MCC, FF-Qmax: [(10.1±5.2)ml/s vs.(16.3±4.7)ml/s, U=-50.11, P<0.01]; PFS-Qmax: [(10.5±3.3)ml/s vs.(13.1±5.0)ml/s, U=-27.54, P<0.05]; PdetQmax: [(16.3±8.6)cmH 2O vs.(37.3±10.3)cmH 2O, U=-84.92, P<0.01]; MCC: [(284.3±71.8)ml vs.(389.6±65.2)ml, U=-39.31, P<0.01], a higher PVR, lower bladder compliance(BC)and a higher incidence of OAB(FF-PVR: [(161.7±79.8)ml vs.(22.0±13.0)ml, U=84.82, P<0.01]; PFS-PVR: [(212.6±83.0)ml vs.(22.2±10.4)ml, U=112.54, P<0.01]; BC: (28.4% vs.7.5%, χ2=6.81, P<0.01); OAB: (27.0% vs.7.5%, χ2=17.62, P<0.01). Conclusions:PD and MSA patients with LUTS have bladder dysfunction.MSA patients have more serious bladder dysfunction than PD patients.

Objective: To investigate the effect of erythropoietin (EPO) on the expression of aquaporin 2-3 after the release of unilateral ureter obstruction in young rats. Methods: Twenty-four SD rats were randomly divided into 3 groups(CUUO-R group, CUUO-R+ EPO group and sham group, with 8 rats in each group). The CUUO-R model was built through unilateral ureteral ligation, after 48 h the obstruction was released.EPO was given to the CUUO-R+ EPO group at the time point of removing obstruction, and then repeated every other day for 1 week, and the same volume of saline was simultaneously given to the CUUO-R rats.The rats in sham group experienced the laparotomy and free dissection of left ureter but not ligation.The kidneys were harvested 7 d after the release of CUUO.The methods of Western blot and immunohistochemistry were used to examine the effects of erythropoietin on the expression of AQP2 and AQP3. Results: The osmotic pressure of CUUO-R+ EPO group was higher than those of CUUO-R group, but lower than that of sham group(P=0.007). The concentration of creatinine and urea in the CUUO-R group[(58.001±2.416) μmol/L and (9.025±1.158) mmol/L]were higher than those of CUUO-R+ EPO group [(57.072±2.286) μmol/L and (1.479±0.043) mmol/L] and sham group [(54.820±1.536) μmol/L and (6.929±0.604) mmol/L]. The differences of the concentration of creatinine and urea between CUUO-R group and sham group were statistically significant(P<0.05). There was no significant difference between CUUO-R+ EPO group and Sham group(P>0.05). The immunohistochemistry showed that the expressions of AQP2 and AQP3 in co-llecting duct in CUUO-R group were significantly weaker than those of in sham group, and the expression of those in CUUO-R+ EPO group were slightly weaker than sham group.These results were further confirmed by Western blot, as the relative quantity of AQP2 and AQP3 were also the lowest in CUUO-R group(AQP2 in 3 groups were 0.974±0.109, 1.923±0.097 and 2.002±0.044, F=392.4, P=0.000; AQP3 in 3 groups were 0.941±0.048, 1.497±0.043 and 1.863±0.043, F=735.8, P=0.000). Conclusions EPO treatment is beneficial for the recovery expre-ssion of AQP2 and AQP3 as well as renal function at the early period after the release of ureteral obstruction in young rats.