ObjectiveTo analyze the epidemiological characteristics and spatial clustering patterns of brucellosis in humans in Zhangjiakou City, Heibei Province from 2018 to 2023, so as to provide a basis for the prevention and control of brucellosis. MethodsIncidence data of brucellosis in Zhangjiakou City from 2018 to 2023 were collected. Descriptive epidemiological analysis, Joinpoint regression modelling, and spatial autocorrelation analysis were used to analyze the temporal trends and spatial clustering patterns of the epidemic. ResultsA total of 3 812 cases of brucellosis were reported in Zhangjiakou City from 2018 to 2023, with no death case, yielding an average annual incidence rate of 15.43/100 000 (incidence range: 12.82/100 000‒17.76/100 000). Cases of brucellosis occurred year-round, with a distinct seasonal pattern, predominantly concentrated between March and September, peaking in May and June. The male-to-female ratio was 2.58∶1, with a higher incidence in males than that in females. The highest incidence rates were observed in the 40‒<50 years (74.98/100 000) and 50‒<60 years age group (87.14/100 000). The majority of cases were farmers and herdsmen (3 557 cases, 93.31%). Joinpoint regression analyses indicated that from 2018 to 2023, the incidence rate of human brucellosis in pastoral areas of Zhangjiakou City showed a declining trend (APC=-9.70%, 95%CI: -15.31%‒ -4.63%), while the incidence rate in mixed-use areas exhibited an increasing trend (APC=6.90%, 95%CI: 0.17%‒14.30%). Spatial clustering analyses showed that the incidence of brucellosis in Zhangjiakou from 2018 to 2023 was non-randomly distributed across the whole city, with a positive spatial correlation and significant clustering (Moran’s I>0, all P<0.001). Local spatial autocorrelation analyses showed that the high-high clusters were concentrated in the pastoral areas during 2018‒2020. From 2021 onward, the number of high-high clusters in mixed and non-pastoral regions exceeded those in traditional pastoral areas. ConclusionFrom 2018 to 2023, the incidence of brucellosis in Zhangjiakou City showed a declining trend, with significant spatial clustering observed across the city. It is recommended to intensify health education among males aged 40‒<60 years. Scientific livestock management practices should be promoted in non-pastoral and mixed areas, and cross-sectoral quarantine and joint prevention and control efforts should be strengthened as well.

[Objective]To explore the effects of electricity on sperm quality,sex hormone levels,and related proteins in TGF-β 1/smads signaling in testicular tissue.[Methods]Forty male SD rats were randomly divided into blank group,model group,electroacupuncture group,and positive drug group.Adenine gavage method was used to establish the model,in the electroacupuncture group,rats received electroacupuncture treatment at the acupoints Zhongji,Guanyuan,Zusanli,and Sanyinjiao once daily for 30 minutes;in the positive drug group,rats were administered L-carnitine oral solution via gavage at a dosage of 10 mL/kg,both intervention groups underwent continuous treatment for 28 days.After treatment,the changes of sperm number,sperm motility rate,follicle-stimulating hormone(FSH),luteizing hormone(LH)and serum sex hormone testosterone(T)were detected by HE staining,and the expression of TGF-β-1/smads signaling pathway in testicular tissue was examined by Western Blot.[Results]Compared to the blank group,the model group showed a significant decrease in sperm count and sperm motility rate(P<0.05),both the electroacupuncture group and the positive drug group exhibited significant increases compared to the model group(P<0.05).Compared to the blank group,the model group had a significant decrease in serum testosterone(T)levels(P<0.05),and significant increases in serum FSH and LH levels(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant increases in serum T levels(P<0.05),and significant decreases in serum FSH and LH levels(P<0.05).The HE staining results showed typical pathological features of AR in the testicular tissue of model group rats,with varying degrees of improvement observed in electroacupuncture and positive drug group rats.Western Blot analysis revealed that in the model group,the protein levels of TGF-β,p-smad2,and p-smad3 in the TGF-β1/smads pathway in testicular tissue were significantly increased(P<0.05);in comparison to the model group,the electroacupuncture group and the positive drug group showed significant decreases in the protein levels of TGF-β,p-smad2,and p-smad3(P<0.05).[Conclusion]Acupuncture can improve the sperm number and sperm motility rate,regulate sex hormone level and improve the spermatogenic environment,and affect the spermatogenesis process via TGF-β 1/smads signaling pathway.

Objective:To analyze the optimal dose of urokinase (UK) for intravenous thrombolysis in Chinese patients with acute ischemic stroke within 4.5 hours of onset.Methods:Based on the intravenous thrombolysis registry for Chinese ischemic stroke within 4.5 hours of onset (INTRECIS) cohort, consecutive patients who received intravenous UK from April 1, 2017 to July 1,2019 were retrospectively collected . According to the tertile dose of UK per body weight, eligible patients were divided into low dose group [(1.00-1.67)×10 4 international unit per kilogram], moderate dose group [(1.68-2.33)×10 4 international unit per kilogram] and high dose group (2.34-3.00)×10 4 international unit per kilogram]. Furthermore, subgroups were analyzed according to age, gender, and baseline National Institutes of Health Stroke Scale (NIHSS) scores. The primary efficacy outcome was excellent functional outcome, defined as a 90-day modified Rankin Scale (mRS) score of 0-1. The secondary efficacy outcomes included favorable functional outcome (mRS score of 0-2 at 90 days), mRS score distribution at 90 days and changes in NIHSS score at 1 day and 14 days, compared with the baseline. The primary safety outcome was symptomatic intracranial hemorrhage (sICH), and the secondary safety outcomes included recurrence of stroke within 90 days, all-cause mortality and any random bleeding events. Results:A total of 1 144 patients were included in the analysis: 549 in the low dose group, 509 in the moderate dose group and 86 in the high dose group. The proportion of excellent functional outcome was higher in the high dose group, compared with the low dose group [79.07% (68/86) vs 67.03% (368/549), OR=2.427, 95% CI 1.280-4.587, P=0.007] and the moderate dose group [79.07%(68/86) vs 70.53%(359/509), OR=1.942, 95% CI 1.023-3.690, P=0.043]. The incidence of sICH was similar among the 3 groups [high dose group vs low dose group: 1.16% (1/86) vs 2.00% (11/549), OR=0.607, 95% CI 0.071-5.153, P=0.648; high dose group vs moderate dose group: 1.16%(1/86) vs 0.79% (4/509), OR=0.330, 95% CI 0.101-1.074, P=0.596]. The subgroup analysis showed that higher proportion of excellent functional outcome was found in the high dose group patients with senior citizens (≥60 years old) [high dose group vs low dose group: 80.70% (46/57) vs 63.07% (222/352), OR=3.401, 95% CI 1.500-7.752, P=0.003; high dose group vs moderate dose group: 80.70% (46/57) vs 69.63% (227/326), OR=2.381, 95% CI 1.074-5.291, P=0.033], moderate neurologic deficit (NIHSS score 4-16) [high dose group vs low dose group:79.07% (34/43) vs 62.61% (211/337), OR=2.604, 95% CI 1.190-5.682, P=0.017; high dose group vs moderate dose group:79.07% (34/43) vs 65.02% (184/283), OR=2.315, 95% CI 1.055-5.097, P=0.036], and large artery atherosclerosis [high dose group vs low dose group: 81.40% (35/43) vs 62.32% (177/284), OR=3.584, 95% CI 1.416-9.009, P=0.007; high dose group vs moderate dose group: 81.40% (35/43) vs 66.06% (144/218), OR=2.793, 95% CI 1.090-7.143, P=0.032]. Conclusions:Intravenous UK dose calculated according to body weight may be reasonable for treating acute ischemic stroke. Intravenous UK with dose of (2.34-3.00)×10 4 international unit per kilogram may favor better benefit for acute ischemic stroke, which warrants further confirmation.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Primary hypomagnesemia with secondary hypocalcemia(HSH) is a rare cause of hypoparathyroidism. This article presents a case of a 26-year-old male with recurrent generalized weakness and tetany, and a literature review of diagnosis and treatment of primary HSH. The biochemical tests revealed the patient had severe hypomagnesemia, mild hypocalcemia, hypokalemia, and hypoparathyroidism. Transient receptor potential melastatin-6(TRPM6) gene mutation were detected by gene test, which confirmed the diagnosis of primary HSH. The patient had been treated with long term oral magnesium supplementation, who remained asymptomatic during the follow-up. Primary HSH is a rare autosomal-recessive disorder caused by mutations in the TRPM6 gene which encoding a magnesium permeable channel expressed in the intestine and the kidney. The primary defect is impaired intestinal absorption of magnesium with secondary renal excretion, leading to a series of clinical symptoms. The treatment is mainly through lifelong magnesium supplementation.

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Objective:To assess the efficacy and safety of cinepazide maleate injection in the treatment of patients with acute ischemic stroke.Methods:A multicenter, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial, led by Peking Union Medical College Hospital, was conducted in 65 Hospitals in China. The efficacy of cinepazide maleate injection in patients with acute anterior circulation cerebral infarction with onset time of ≤48 hours, 7≤National Institute of Health stroke scale (NIHSS) score ≤25 was assessed from August 2016 to February 2019, using the proportion of modified Rankin scale (mRS) score≤1 and Barthel index (BI) score≤95 on day 14 as efficacy endpoint. The patients were divided into treatment group who were treated with cinepazide maleate injection and control group who were treated with placebo.Results:A total 937 patients were involved in the final efficacy analysis (466 in treatment group and 471 in control group). The proportion of subjects with mRS score≤1 on day 14 after treatment were higher in the treatment group than that in the control group (102/466(21.89%) vs76/471(16.14%)). Logistic regression analysis showed that patients treated with cinepazide maleate were significantly more likely to have a favorable outcome (mRS score≤1) than patients treated with placebo on day 14 ( OR=0.677, 95% CI 0.484-0.948 , P=0.023), and patients treated with cinepazide maleate were more likely to reach independence in activities of daily living (Barthel Index ≥95) than those treated with placebo on day 14 (125/466(26.82%) vs 91/471(19.32%); OR=0.632, 95% CI0.459-0.869, P=0.005). The rate of adverse events was similar between the treatment and control groups. Conclusion:The 14-day treatment with cinepazide maleate injection could reduce the degree of disability whereas did not increase the risk of adverse events.

Objective:To investigate the effect of oxycodone hydrochloride injection pretreatment on focal cerebral ischemia-reperfusion injury in rats.Methods:Seventy-two male SD rats weighing 200-250 g were randomly divided into 3 groups( n=24 each group): sham operation group (sham group), focal cerebral I/R group (I/R group), and oxycodone hydrochloride injection group (Oxy group). Focal cerebral I/R was induced by middle cerebral artery occlusion for 2 h followed by reperfusion. In the Oxy group, oxycodone hydrochloride 0.5 mg/kg was injected iv at 5 min before ischemia. While the same volume of saline (1 mL) was injected in the sham group and I/R group. The neurological deficit score (NDS) was assessed at 24 h of reperfusion, the rats were then sacrificed, and their brains were immediately removed for determination of brain water content and the infarct volume, and the histopathological changes were observed after HE staining. The levels of cytokines (TNF-α, IL-1β and IL-10) in the ischemia cortex were quantified by ELISA. MPO activity in the ischemia cortex was assessed. Western blot was used to detect the expression of NF-κB in the ischemia cortex. The data were analyzed using SPSS 20.0 software, multiple-group comparisons were performed using one-way ANOVA, and LSD- t test was used for pairwise comparison between groups. A P<0.05 was considered statistically significant different. Results:Compared with the sham group, NDS, brain water content, relative infarction volume and rate of nerve cell necrosis were significantly increased in the I/R and Oxy groups (all P<0.05). Levels of TNF-α, IL-1β, IL-10, NF-κB and the activities of MPO were increased in the ischemia cortex (all P<0.05). Compared the Oxy group with the I/R group, NDS, brain water content, relative infarction volume and rate of nerve cell necrosis were significantly decreased [(1.7±0.9) vs (2.6±1.1);(79.2±2.4)% vs (84.7±4.2)%; (23.0±5.4)% vs (34.8±6.0)%; (25.2±12.4)% vs (54.8±14.8)%, all P<0.05]. The levels of TNF-α, IL-1β, relative expression of NF-κB, and the activities of MPO were significantly decreased in the ischemia cortex [(4.4±1.2) pg/mg vs (6.5±1.2) pg/mg; (5.4±0.7) pg/mg vs (7.8±0.8) pg/mg; (0.83±0.11) vs (1.23±0.33); (0.27±0.09) U/g vs (0.36±0.14) U/g, all P<0.05] , while the concentration of IL-10 was significantly increased [(20.9±4.5) pg/mg vs (9.2±1.6) pg/mg, t=6.036, P=0.000 1]. Conclusions:Oxycodone hydrochloride can attenuate focal cerebral I/R injury through inhibiting NF-κB activity.

Objective: To evaluate the effect of irisin preconditioning on global cerebral ischemia-reperfusion (I/R) injury in rats. Methods: Thirty-six healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 3 groups (n=12 each) using a random number table method: sham operation group (group S), global cerebral I/R group (group I/R) and irisin preconditioning group (group I). Global cerebral I/R was induced by occlusion of bilateral common carotid arteries combined with hypotension (MAP maintained at 35-45 mmHg) in anesthetized rats.At 30 min before ischemia, irisin 10 μg/kg (diluted to 10 μg/ml in normal saline) was intravenously injected in group I, and the equal volume of normal saline was intravenously injected in S and I/R groups.Morris water maze test was performed at day 3 of reperfusion to assess the cognitive function.Rats were sacrificed after the end of morris water maze test, and brains were removed for determination of histopathologic changes in hippocampal CA1 region (using HE staining), neuronal apoptosis in hippocampal CA1 region (Tunel staining), glial fibrillary acidic protein (GFAP) expression (by Western blot), myeloperoxidase (MPO) activity in the hippocampal tissues (by colorimetric assay), and contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in hippocampal tissues (by enzyme-linked immunosorbent assay). The cell necrosis rate and apoptotic rate were calculated. Results: Compared with group S, the escape latency was significantly prolonged on 1-5 days in group I/R and on 1-3 days in group I, the time of staying at 1st quadrant was significantly shortened, the cell necrosis rate and apoptotic rate were increased, the expression of GFAP was up-regulated, and the activity of MPO and contents of TNF-α and IL-1β were increased in I/R and I groups (P<0.05 or 0.01). Compared with group I/R, the escape latency was significantly shortened on 1-5 days, the time of staying at 1st quadrant was prolonged, the cell necrosis rate and apoptotic rate were decreased, the expression of GFAP was down-regulated, and the MPO activity and contents of TNF-α and IL-1β were decreased in group I (P<0.05 or 0.01). Conclusion Irisin preconditioning can reduce the global cerebral I/R injury in rats, and the mechanism may be related to inhibiting activation of astrocytes in hippocampus and reducing inflammatory responses.

Objective To evaluate the effect of oxycodone on acute lung injury (ALI) induced by lipopolysaecharide (LPS) in rats. Methods Thirty-six pathogen-free healthy male Sprague-Dawley rats, weighing 250-300 g, were divided into 3 groups (n= 12 each) using a random number table: sham opera-tion group (group S), LPS-induced ALI group (group A) and oxycodone group (group O). ALI was in-duced by injecting LPS 8 mg∕kg intravenously in A and O groups, while the equal volume of normal saline was given instead in group S. Oxycodone 2 mg∕kg was injected intravenously at 10 min before LPS injection in group O, while the equal volume of normal saline was given instead in S and A groups. Rats were sacri-ficed at 6 h after LPS injection, and the broncho-alveolar lavage fluid (BALF) was collected for detection of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) concentrations by enzyme-linked im-munosorbent assay. Pulmonary specimens were obtained for microscopic examination of the pathological changes and for determination of wet∕dry weight ratio (W∕D ratio) and expression of Toll-like receptor 4 (TLR4) in lung tissues (using real-time polymerase chain reaction and Western blot). Results Compared with group S, the TNF-α and IL-1β concentrations in BALF, W∕D ratio, pathological scores and expres-sion of TLR4 were significantly increased at 6 h after LPS injection in A and O groups (P<0. 05). Com-pared with group A, the TNF-α and IL-1β concentrations in BALF, W∕D ratio, pathological scores and expression of TLR4 were significantly decreased at 6 h after LPS injection in group O (P<0. 05). Conclu-sion Oxycodone can attenuate LPS-induced ALI in lung tissues, and the mechanism is related to down-regulating the expression of TLR4 and inhibiting inflammatory responses of rats.