Epidemiological characteristics of norovirus acute gastroenteritis outbreaks and influencing factors in China, 2007-2021 / 中华流行病学杂志

Objective: To analyze the epidemiological characteristics of norovirus-caused acute gastroenteritis outbreaks in China, identify the factors influencing the scale of outbreaks, and provide scientific evidences for early control of norovirus infection outbreaks. Methods: The descriptive epidemiological analysis approach was applied to analyze the incidence of national norovirus infection outbreaks by using the data from the Public Health Emergency Event Surveillance System in China from January 1, 2007 to December 31, 2021. The unconditional logistic regression model was applied to analyze the risk factors that affected the outbreaks' scale. Results: A total of 1 725 norovirus infection outbreaks were recorded in China from 2007 to 2021, with an upward trend in the number of the reported outbreaks. The southern provinces had their annual outbreak peaks from October to March; the northern provinces had two outbreak peaks from October to December and from March to June annually. The outbreaks occurred mainly in southeastern coastal provinces with a trend of gradual spread to central, northeastern and western provinces. The outbreaks mainly occurred in schools and childcare setting (1 539 cases, 89.22%), followed by enterprises and institutions (67 cases, 3.88%) and community households (55 cases, 3.19%). Human to human transmission was the main infection route (73.16%), and norovirus GⅡ genotype was the predominate pathogen causing the outbreaks (899 cases, 81.58%). The time interval between the onset of the primary case and the outbreak reporting M (Q1, Q3) was 3 (2, 6) days and the case number of the outbreak M (Q1, Q3) was 38 (28, 62). The timeliness of outbreak reporting was improved in recent years and the scale of the outbreaks showed a decreasing trend over the years, the differences in reporting timeliness and outbreak scale among different settings were significant (P<0.001). The factors that affected outbreaks' scale included the outbreak setting, transmission route, outbreak reporting timeliness and type of living areas (P<0.05). Conclusions: From 2007 to 2021, the number of the norovirus-caused acute gastroenteritis outbreaks increased in China and the more areas were affected. However, the outbreak scale showed a decreasing trend and the outbreak reporting timeliness was improved. It is important to further improve the surveillance sensitivity and reporting timeliness for the effective control of the outbreak scale.

A new method of microglia sorting and functional characteristics of spinal microglia in aged rats / 中国应用生理学杂志

Objective: To establish an improved method of separating microglia from aged rats and to observe the biological characteristics of spinal microglia of aged rats. Methods: Young SD rats (2 months) were used as control group. Single cell suspension of rat microglia were prepared by trypsin, trypsin substitutes or mechanical net rubbing method. Then, by assessing the purity and survival rate of cells, and observing the morphological characteristics and analyzing the inflammatory functional characteristics, we optimized the isolation and purification method of microglia from aged rats (20 months old) , and observed the functional characteristics of spinal microglia in aged rats. Results: The survival rate of cells digested by pancreatic enzyme was low(young rats 83%, aged rats 60%). Although the survival rate of mechanical net rubbing method was higher than that of pancreatic enzyme digest methods (95%), the cell acquisition rate was lower(young rats(0.207±0.020)×106, aged rats(0.243±0.023)×106). Trypsin substitute dissociation combining density gradient centrifugation method was the best way to get abundant, active and higher survival microglia, and the purity reached more than 85%. We used this method to separate microglia from spinal cord of rats. Compared with the young rats, the spinal cord tissue of old rats was larger, the digestive fluid volume was higher, but the digestion time was shorter. Compared with the young rats, the aged rat spinal microglia had larger and rounder cell body, fewer and shorter protrusions, it tended to be activated morphologically, the level of proinflammatory cytokine IL-1β of microglia in aged rats was lower, and the level of antiinflammatory factor IL-10 was higher. Conclusion: The method of trypsin substitute dissociation combined with density gradient centrifugation was successfully established to isolate and purify microglia from spinal cord of rats, the spinal microglia of old rats showed anti-inflammatory phenotype.

A comparative study of microwire electrode array with built-in and external reference electrodes / 中国应用生理学杂志

Objective: To compare the difference between the built-in and external reference electrode of microwire electrode array in the process of recording rat brain neuron firings, optimizing the production and embedding of the microwire electrode array, and providing a more affordable and excellent media tool for multi-channel electrophysiological real-time recording system. Methods: A 16 channel microwire electrode array was made by using nickel chromium alloy wires, circuit board, electrode pin and ground wires (silver wires). The reference electrode of the microwire electrode array was built-in (the reference electrode and electrode array were arranged in parallel) or external (the reference electrode and ground wire were welded at both ends of one side of the electrode), and the difference between the two electrodes was observed and compared in recording neuronal discharges in ACC brain area of rats. Experimental rats were divided into built-in group and external group, n=8-9. The test indicators included signal-to-noise ratio (n=8), discharge amplitude (n=380) and discharge frequency (n=54). Results: The microwire electrode array with both built-in and external reference electrodes successfully recorded the electrical signals of neurons in the ACC brain region of rats. Compared with the external group, the electrical signals of neurons in built-in group had the advantages of a higher signal-to-noise ratio (P＜0.05), a smaller amplitude of background signals and less noise interference, and a larger discharge amplitude(P＜0.05); there was no significant difference in spike discharge frequency recorded by these two types of electrodes (P＞0.05). Conclusion: When recording the electrical activity of neurons in the ACC brain region of rats, the microwire electrode array with built-in reference electrode recorded electrical signals with higher signal-to-noise ratio and larger discharge amplitude, providing a more reliable tool for multi-channel electrophysiology technology.

Behavioral-electrophysiological observation of the involvement of dopamine D1 receptor of the rat anterior cingulate cortex in the regulation of pain-related emotion / 生理学报

The present study was aimed to explore the involvement of dopamine D1 receptor of the anterior cingulate cortex (ACC) in the regulation of chronic inflammatory pain-related emotion. On the first day, the rats were acclimated to the environment and the baseline indices were measured. On the second day, the rats were administered with the dopamine D1 receptor antagonist SCH-23390 or agonist SKF38393 in the ACC, and then they were subcutaneously injected with complete Freund's adjuvant (CFA, 0.08 mL) in the left hind paw to establish conditioned place avoidance (CPA) response after pairing with specific environment. On the third day, the CPA response and the firing frequency of ACC neurons were observed synchronously, and the open-field behavior, mechanical pain behavior and paw withdrawal latency (PWL) tests were also observed subsequently. In other experiments, rats were given subcutaneous injection of normal saline (NS) on the left hind paw after SCH-23390 or SKF-38393 was administered in the ACC, and then the same observations were performed. The results showed that: (1) Compared with the control group, the PWL and mechanical pain thresholds of rats injected with CFA on the left hind paw were significantly decreased (P < 0.05); (2) The residence time of rats injected with CFA in the "pain environment" and open field center was significantly shortened (P < 0.05); (3) Pre-injection of antagonist SCH-23390 in ACC (10 μg) alleviated the anxiety-like negative behavior response induced by CFA (P < 0.05) and reversed CFA-induced increases of discharge frequency of ACC neurons (P < 0.05); (4) Pre-injection of agonist SKF-38393 in the ACC (10 μg) induced CPA-like behavioral response in rats injected with NS in the left hind paw, and increased the firing frequency of ACC neurons (P < 0.05); (5) Immunofluorescence detection showed that dopamine D1 receptor and NMDA receptor were co-expressed in the same neuron. These results suggest that inhibition of dopamine D1 receptor in ACC can alleviate the negative emotional response induced by persistent pain.

Study on the association between prenatal examinations of Tibetan pregnant women and low birth weight infants / 中华疾病控制杂志

Objective To understand the relationship between the number of prenatal examination during pregnancy in Tibetan mothers and low birth weight infants, and to provide reference for improving the quality of antenatal care and reducing the incidence of low birth weight infants. Methods Tibetan women and newborns who gave birth in a hospital in Lhasa, Tibet from January 2012 to December 2018 were selected as research objects. The basic data, delivery materials and newborn data of all single births were collected. Logistic regression models were used to analyze the relationship between the number of maternal prenatal examinations and the birth weight of the newborn. Results In 5 563 pregnant women, the prenatal check-up rate was 10.48%. Among the newborns, low birth weight accounted for 11.32%. With the increase in the number of maternal births, the neonatal low birth weight rate showed a downward trend ( 2=14.57, P=0.002). Multivariate Logistic regression model showed that after controlling for maternal age, fetal gender, mode of delivery, fetal asphyxia and other confounding factors, the number of low prenatal examinations was still related to the occurrence of low birth weight infants. The incidence of low birth weight infants who gave birth to antenatal check-ups and 1-2 prenatal visits was 1.41 times (95% CI: 1.00-1.98) and 2.34 times (95% CI: 1.09-5.02) higher than those who received standardized prenatal checkups. Conclusions Tibetan pregnant women receive a lower proportion of standardized prenatal examination and there is a higher risk of low birth weight infants. It is recommended to strengthen the quality of maternal and child health care work in minority areas to ensure maternal and child safety.

Influence of general anesthetic exposure in developing brain on cognition and the underlying mechanisms / 生理学报

With the evolution of medical techniques and technology, an increasing number of infants, neonates, and fetuses are exposed to general anesthesia for clinical diagnostic and therapeutic process. The neurotoxic effects of general anesthetics on developing brain have been a subject of concern and considerable research interest. Population-based study confirmed that single short-term general anesthetic exposure does not affect nervous system function, but multiple exposures to general anesthesia could damage cognitive function. Animal studies further discovered the underlying mechanisms. Nervous system is most susceptible to general anesthetics during the brain growth spurt. The time-point is more critical than the duration of exposure to general anesthetics. General anesthetics can induce intracellular calcium overload, disturb energy metabolism, promote cell apoptosis and lead to cell loss. General anesthetics can damage synaptic structure, transmission and plasticity, and impair brain function. High throughput omics technologies have been used to screen the differentially expressed genes induced by general anesthetics, which provide further understanding of the mechanism of general anesthetics affecting cognitive function. This review provides an update on the pathophysiologic mechanisms underlying the anesthesia-neurotoxicity, which will be helpful to provide instructions for the clinical use of general anesthesia in children.

Identification of Seven Novel Mutations in the Acid Alpha-glucosidase Gene in Five Chinese Patients with Late-onset Pompe Disease / 中华医学杂志(英文版)

<p><b>Background</b>Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene (GAA). A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease (LOPD) who carried novel GAA gene mutations.</p><p><b>Methods</b>Clinical and pathological data of patients diagnosed with glycogen storage disease at our institution from April 1986 to August 2017 were collected, and next-generation sequencing of frozen muscle specimens was conducted.</p><p><b>Results</b>Of the five patients included in the study, the median disease onset age was 13 years, with a median 5 years delay in diagnosis. The patients mainly manifested as progressive weakness in the proximal and axial muscles, while one patient developed respiratory insufficiency that required artificial ventilation. In muscle biopsies, vacuoles with variable sizes and shapes appeared inside muscle fibers, and they stained positive for both periodic acid-Schiff and acid phosphatase staining. Ten GAA gene mutations, including seven novel ones (c.796C>A, c.1057C>T, c.1201C>A, c.1780C>T, c.1799G>C, c.2051C>A, c.2235dupG), were identified by genetic tests.</p><p><b>Conclusions</b>The seven novel GAA gene mutations revealed in this study broaden the genetic spectrum of LOPD and highlight the genetic heterogeneity in Chinese LOPD patients.</p>

A Novel Mutation of Mitochondrial T14709C Causes Myoclonic Epilepsy with Ragged Red Fibers Syndrome in a Chinese Patient / 中华医学杂志(英文版)

<p><b>Background</b>Myoclonic epilepsy with ragged red fibers (MERRF) syndrome is characterized by myoclonus, generalized epilepsy, cerebellar ataxia, and ragged red fibers (RRFs) in the muscle. T-to-C transition at nucleotide position 14709 in the mitochondrial tRNA glutamic acid (tRNA) gene has previously been associated with maternally inherited diabetes and deafness. However, the association between MERRF and mitochondrial T14709C mutation (m.T14709C) has never been reported before.</p><p><b>Methods</b>Clinical information of a 17-year-old patient was collected; muscle biopsy and next-generation sequencing (NGS) of whole mitochondrial and neuromuscular disease panel were then conducted. Finally, sanger sequencing was carried out to confirm the mutations.</p><p><b>Results</b>The patient presented a typical MERRF phenotype with muscle weakness, epileptic seizure, clonic episodes, cerebellar ataxia, and spinal scoliosis. Muscle biopsy showed RRFs which indicated abnormal mitochondrial functions. NGS of whole mitochondrial gene revealed m.T14709C mutation, confirmed by Sanger sequencing.</p><p><b>Conclusion</b>We present a sporadic patient with typical MERRF presentation carrying the mutation of m.T14709C, which expanded the spectrum of m.T14709C.</p>

Experimental study on expression of connective tissue growth factor in viral myocarditis in mice / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the expression of connective tissue growth factor (CTGF) in the myocardial tissue of mice with viral myocarditis (VMC).</p><p><b>METHOD</b>Balb/c mice were infected with coxsackie virus B3 (CVB3) to establish VMC model. The mice were divided into control group (n = 50) and VMC group (n = 50). on days 4, 7, 14 and 21 after infection, heart specimens of 8 mice were randomly taken and examined after HE staining for myocardial necrosis and cellular infiltration. The area of positive Masson stained myocardium collagen fibers was measured, and collagen volume fraction (CVF) was measured. Then the level of serum creatine phosphokinase-MB (CKMB) was determined. The levels of CTGF and TGF-β₁ were detected by streptavidin peroxidase immunoperoxidase technique. Expression of CTGF and TGF-β₁ were detected with reverse transcription-polymerase chain reaction (RT-PCR). At the same time, the correlations were analyzed.</p><p><b>RESULT</b>(1) The level of CKMB peaked on day 7, and decreased afterwards (455.45 ± 37.95, 606.95 ± 35.64, 573.62 ± 42.90, 308.60 ± 20.49, respectively, 4 - 21 d points), in which 4, 7, 14 d points, there was significant difference compared with control group (t = 6.144, 12.558, 11.182, respectively, P < 0.01). (2) CVF increased significantly on day 14 (8.22 ± 1.95, t = 4.486, P < 0.01) and day 21 (9.46 ± 1.87, t = 4.486, P < 0.01) in VMC group. (3) Measured by streptavidin peroxidase immunoperoxidase technique, the levels of CTGF (171.50 ± 10.25, 141.70 ± 10.863, 110.35 ± 11.051, 81.05 ± 10.190, respectively, 4 - 21 d points) and TGF-β₁ (184.90 ± 11.480, 150.25 ± 9.915, 103.50 ± 10.455, 84.15 ± 9.848, respectively, 4 - 21 d points) increased after day 4 in VMC (P < 0.01). (4) Measured by RT-PCR, the expression of CTGF mRNA and TGF-β₁ increased in VMC group, and the increase was enhanced with the disease development (P < 0.01). (5) The expression of CTGF and TGF-β₁ was positively linearly correlated (r = 0.987, P < 0.01), the expression of CTGF was negatively correlated with CVF (r = -0.901, P < 0.01), but the expression of CTGF was detected earlier than myocardial fibrosis.</p><p><b>CONCLUSION</b>The increase of CTGF expression was associated with the severity of myocardial fibrosis in VMC. These results suggest that abnormal expression of CTGF may take part in the development of fibrosis in VMC.</p>