Transmission in Latent Period Causes A Large Number of Infected People in the United States

The cumulative number of confirmed cases in the United States exceeded one million on 29 April 2020, becoming the country of the most serious pandemic in the world. We proposed a model to analyze the real situation and follow-up trend of the epidemic in the US. The proposed model divides the epidemic period into two phases, and includes three different categories of transmitters: the latent population, the documented infectious population, and the undocumented infectious population. We use metapopulation network to simulate the spread of the COVID-19 in the US, and apply the Bayesian inference to estimate the key parameters of the model. We also perform component analysis and sensitivity analysis, researching the compositions of the people with COVID-19. The results show that the basic reproduction number in the early period of propagation is 4.06. As of April 13, 2020, only 45% (95% CI: 35% - 73%) of symptom onset cases in the United States were documented. The incubation period of COVID-19 is 10.69 days (95% CI: 10.02 - 11.74). If the current level of interventions is continued, the cumulative number of confirmed cases is expected to reach more than 1.7 million in July and continue to grow.

Assessing the Global Tendency of COVID-19 Outbreak

COVID-19 is now widely spreading around the world as a global pandemic. In this report, we estimated the global tendency of COVID-19 and analyzed the associated global epidemic risk, given that the status quo is continued without further measures being taken. Based on official data of confirmed and recovered cases until May 21, 2020, the results showed that the global R0, excluding China, was estimated to be 2.76 (95% CI: 2.57 - 2.95). The United States, Germany, Italy, and Spain have peak values over 100,000. Using dynamical model and cluster analysis, we partition the globe into four regional epicenters of the outbreak: Southeast Asia extending southward to Oceania, the Middle East, Western Europe, and North America. Among them, Western Europe would become the major center of the outbreak. The peak values in Germany, Italy, and Spain were estimated to be 228,000, 291,000, and 298,000, respectively. Based on the current control measures by May 21, 2020, the peak value in the United States will reach 2,114,000. The cumulative number of 51 mainly researched countries patients might finally attain 6,542,000 (95% CI: 4,772,000 - 40,735,000). We also estimated the diagnosis rate, recovery rate, and infection degree of each country or region, and used clustering algorithm to retrieve countries or regions with similar epidemic characteristics. Several suggestions have been proposed for countries or regions in different clusters.

Estimating the Efficacy of Traffic Blockage and Quarantine for the Epidemic Caused by 2019-nCoV (COVID-19)

BackgroundSince the 2019-nCoV (COVID-19) outbreaks in Wuhan, China, the cumulative number of confirmed cases is increasing every day, and a large number of populations all over the world are at risk. The quarantine and traffic blockage can alleviate the risk of the epidemic and the infections, henceforth evaluating the efficacy of such actions is essential to inform policy makers and raise the public awareness of the importance of self-isolation and quarantine. MethodWe collected confirmed case data and the migration data, and introduced the quarantine factor and traffic blockage factor to the Flow-SEIR model. By varying the quarantine factor and traffic blockage factor, we simulated the change of the peak number and arrival time of infections, then the efficacy of these two intervation measures can be analyzed in our simulation. In our study, the self-protection at home is also included in quarantine. ResultsIn the simulated results, the quarantine and traffic blockage are effective for epidemic control. For Hubei province, the current quarantine factor is estimaed to be 0.405, which means around 40.5% of suceptibles who are close contacting with are in quarantine, and the current traffic blockage factor is estimaed to be 0.66, which indicates around 34% of suceptibles who had flowed out from Hubei. For the other provinces outside Hubei, the current quarantine factor is estimated to be 0.285, and the current traffic blockage factor is estimated to be 0.26. With the quarantine and traffic blockage factor increasing, the number of infections decrease dramatically. We also simulated the start dates of quarantine and traffic blockage at four time points, the simulated results show that the early of warning is also effective for epidemic containing. However, provincial level traffic blockage can only alleviate 21.06% - 22.38% of the peak number of infections. In general, the quarantine is much more effective than the traffic blockage control. ConclusionBoth of quarantine and traffic blockage are effective ways to control the spread of COVID-19. However, the eff icacy of quarantine is found to be much stronger than that of traffic blockage. Considering traffic blockage may also cause huge losses of economy, we propose to gradually deregulate the traffic blockage, and improve quarantine instead. Also, there might be a large number of asymptomatic carriers of COVID-19, the quarantine should be continued for a long time until the epidemic is totally under control.

EPIDEMIC TRENDS ANALYSIS AND RISK ESTIMATION OF 2019-NCOV OUTBREAK

Since December 1, 2019, the spread of COVID-19 is increasing every day. It is particularly important to predict the trend of the epidemic for the timely adjustment of the economy and industries. We proposed a Flow-SEHIR model in this paper to perform the trends of 2019-nCoV (COVID-19) in China. The results show that the number of daily confirmed new cases reaches the inflection point on Feb. 6 - 10 outside Hubei. For the maximum of temporal infected cases number, the predicted peak value in China except Hubei was estimated to be 21721 (95% CI: 18764 - 24929). The peak arrival time is on March 3 - 9. The temporal number of patients in most areas of China outside Hubei will peak from March 12 to March 15. The peak values of more than 73.5% provinces or regions in China will be controlled within 1000. According to Flow-SEHIR model and estimations from the data of evacuation of nationals from Wuhan, the real peak cumulative number of patients in Hubei is estimated to be 403481 (95% CI: 143284 - 1166936).

Effects of Simvastatin Combined with Rivaroxaban on Pharmacokinetics of Rivaroxaban in Rats / 中国药房

OBJECTIVE： To study the effects of simvastatin combined with rivaroxaban on pharmacokinetics of rivaroxaban in rats. METHODS： Thirty rats were randomly divided into rivaroxaban group （intragastric administration of normal saline+rivaroxaban 2.6 mg/kg）， simvastatin+rivaroxaban group （intragastric administration of simvastatin 5.3 mg/kg+rivaroxaban 2.6     mg/kg）， with 15 rats in each group. The rats were given normal saline/simvastatin intragastrically for 5 d， once a day， and then given intragastric administration of rivaroxaban+normal saline/simvastain once. The blood samples were collected from orbital cavity of rats before medication and 0.25， 0.5， 0.75， 1， 1.5， 2， 4， 8， 12， 24 h after medication. The plasma concentration of rivaroxaban was determined by LC-MS/MS. Plasma concentration-time curves were drawn， and the pharmacokinetic parameters were fitted by DAS 2.1.1 software. RESULTS： The pharmacokinetic parameters of rivaroxaban group and simvastatin+rivaroxaban group in rats included that AUC0-24 h were （2 599.86±791.82） and （2 777.74±989.25） ng·h/mL； AUC0-∞ were （3 053.28±        1 116.06） ng·h/mL and （3 396.78±1 409.80） ng·h/mL； t1/2 were （8.06±3.52） h and （9.25±4.18） h； tmax were（0.65±0.28） h and （0.60±0.13） h； CLZ were （0.95±0.32） L/（h·kg） and （0.88±0.34） L/（h·kg）； Vd were（10.37±4.43） L/kg and （11.07±4.48）      L/kg； cmax were （424.93±145.30） ng/mL and （507.15±132.40） ng/mL. Compared with rivaroxaban group， AUC0-24 h， AUC0-∞， t1/2， Vd and cmax of simvastatin+rivaroxaban group increased by 6.40％， 10.11％， 12.86％， 6.32％， 16.21％； tmax and CLZ decreased by 8.33％ and 7.95％. There was no significant difference （P＞0.05）. CONCLUSIONS： There is no significant change in pharmacokinetic parameters of rivaroxaban in rats after combination of simvastatin （5.3 mg/kg） and rivaroxaban （2.6 mg/kg）.

Total hip arthroplasty for Crowe type IV developmental dysplasia of hip in adults / 中国组织工程研究

BACKGROUND:Total hip arthroplasty is an optimal choice for patients with late hip dysplasia. Crowe type IV developmental dysplasia of the hip increases the difficulty of the operation, and the surgery is controversial. OBJECTIVE:To evaluate the clinical effects of total hip arthroplasty on Crowe type IV developmental dysplasia of the hip and the method of reconstruction of acetabulum and the treatment of proximal femur. METHODS:A total of 12 patients (14 hips) with Crowe type IV developmental dysplasia of the hip underwent total hip arthroplasty. Preoperative Harris hip score was averagely (35.0±6.8) points. Al hips were treated with smal acetabular components combined with medial protrusion technique in acetabular reconstruction, as wel as subtrochanteric shortening osteotomy in femur. Joint function of hips was evaluated according to the Harris hip score. RESULTS AND CONCLUSION:Al patients were fol owed up with an average of 4.6 years (ranged 1 to 7 years). Two cases (two hips) suffered from infraction of greater trochanter of femur during replacement, and it was fixed with wire. There was complete sciatic nerve injury in one case, which partial y restored after conservative treatment for 1 month. No infection, prosthesis loosening, or deep venous thrombosis with obvious clinical manifestations was visible. Bone union was observed at the site undergoing osteotomy at the side of femur. After replacement, final fol ow-up showed that Harris hip score was averagely (84.0±7.0) points. The mean amount of postoperative leg lengthening was 5 cm (range 4-6 cm). Shortened limbs were corrected satisfactorily. These results suggested that total hip arthroplasty using smal acetabular component, medial protrusion, and femoral subtrochanteric shortening osteotomy technique for the Crowe type IV developmental dysplasia of the hip can effectively restore hip function and leg length. The long-term curative effects require further investigations.

Effects of brain focal ischemia or chronic stress on the hippocampus-dependent learning and memory function / 中华神经科杂志

Objective To compare the intensity of cognitive impairment and the level of pathological lesion in hippocampus induced by ischemia or chronic stress for a more valuable guidance in the treatment of post-stroke cognitive impairment(PSCI).Methods Forty male adult SD rats were divided medially into 4 groups:control,stress,ischemia and ischemia plus stress.Animals in 3 treatment groups were subjected respectively to an operation of modified selective middle cerebral artery occlusion or a procedure of continuous 3-week chronic unpredictable mild stress or a combined program of the two treatments.Morris water maze was employed to assess hippocampus-dependent learning and memory function and the brain-derived neurotrophic factor(BDNF)expression was detected by immunohistochemical staining in CA3 area and the mRNA amplification through semi-quantitative reverse transcription polymerase chain reaction(RT-PCR).Results Both chronic stressors and ischemia could significantly decrease the learning and memory function in rats like the escape latency in the performance of the Morris water maze test compared with the controL The stress group was related preferentially to a more severe deterioration in the learning function but not statistically in the memory loss as compared to ischemia group.The cognitive function decreased more markedly in rats when suffered the chronic unpredictable mild stresses plus ischemia,In comparison to control,ischemia significantly increased BDNF+ cells in hippocampal CA3 area (27.0 ±2.5 vs 20.1 ±2.1),while stress markedly reduced the expression of BDNF(15.2 ± 1.8 vs 20.1 ±2.1).Their combined effects still statistically led to a reduction in BDNF expression(8.2 ± 1.5,F =52.87,P ＜0.05).The same tendency was found in BDNF mRNA expression.Conclusions Stress may preferentially and powerfully influence hippocampus-dependent cognitive function compared with ischemia and the combination of focal ischemia and stress leads to the most impairments in cognition and hippocampal BDNF expression.Data suggest that more attention should be given to the strategies to increase the resistance to psychosocial stressors and decrease the depressed symptoms for a full PSCI recovery.

Blood glucose control in a patient with diabetes mellitus after facial composite allotransplantation / 中华全科医师杂志

A facial allotransplanted patient presented hyperglycemia with blood glucose ranged 14. 3 -33. 3 mmol/L after receiving immunosuppressive drugs and glucocorticoids. To control the blood glucose level, the patient was treated with two subcutaneous doses of 10 U human neutral protamine hagedorn (NPH) insulin, and the fasting glucose level came down to 3. 6 - 9. 4 mmol/L. Then the continuous subcutaneous infusion of insulin aspart ( Novo Industri) was administrated (from 96 to 21 U/d) , and the fasting blood glucose levels were 3. 9 -4. 6 mmol/L. With oral administration of Metformin and Repaglinide, the fasting blood glucose was maintained to 4. 3 -5.9 mmol/L. With these medications, the blood glucose level of the patient was under good control and the acute and chronic complications of hyperglycemia were effectively prevented.

The optimum flow shear stress and the mass transport benefiting for construction of the tissue-engineered bone combining computational fluid dynamics / 中华骨科杂志

Objective To explore the optimum flow shear stress and mass transport for the construction of tissue-engineered bone.Methods The β-tricalcium phosphate (β-TCP) scaffolds seeded with human bone marrow-derived mesenchymal stem cells (HBMMSCs) were cultured in perfusion bioreactor.When the same flow rate was applied,the flow shear stress was separately 1×,2× and 3×.When the same flow shear stress was applied,the flow rates were separately 3 ml/min,6 ml/min and 9 ml/min.Cell proliferation was measured by MTT method.The construction of tissue-engineered bone was evaluated by measuring alkaline phosphatase (AKP) activity,secretion of osteopontin (OP) and osteocalcin (OC),and the mineralization of extracellular matrix (ECM).The flow shear stress and the mass transport were obtained using computational fluid dynamics.Results When the flow rate was same,the most cell proliferation was found in 2× group.The AKP activity and secretion of OC was higher in 2× and 3× groups than in those in 1× group.After 28days,the highest amount of mineralization of ECM was found in 3× group.When the flow shear stress was same,the AKP activity was highest in 6 ml/min group.After 28 days,secretion of OC and formation of mineralized ECM was highest in 3 ml/min group.When the flow rate was same,the flow shear stress was separately 0.004-0.007 Pa,0.009-0.013 Pa and 0.013-0.018 Pa.When the flow shear stress was same,the flow rate was separately 0.267-0.384 mm/s,0.521-0.765 mm/s and 0.765-1.177 mm/s.Conclusion When the tissue-engineered bone was constructed,0.013-0.018 Pa flow shear stress and 0.267-0.384 mm/s mass transport velocity could improve the construction of the tissue-engineered bone in vitro.

Effects of sex steroid hormones, thyroid hormone levels, and insulin regulation on thyrotoxic periodic paralysis in Chinese men.

Our study is to determine the expression of thyroid hormone, sex hormone, insulin, and C-peptide in Chinese male patients with thyrotoxic periodic paralysis (TPP). This study covered 102 patients with hyperthyroidism from Xijing Hospital. According to whether occurrence of TPP or not, patients were divided into two groups (those that were hyperthyroid with and without TPP) that were, matched with age, blood pressure, urea, and creatinine. We found the body mass index (BMI) in patients with TPP was higher than that in pure hyperthyroidism patients. The levels of the total thyroxine (T4), free triiodothyronine (FT3), and free thyroxine (FT4) were significantly lower in patients with TPP compared with pure hyperthyroidism patients, while serum testosterone levels were higher compared with pure hyperthyroidism patients. Moreover, after glucose administration, the concentration of insulin at 60, 120, and 180 min were significantly higher in patients with TPP than those in pure hyperthyroidism patients. The insulin area under the curve (AUC) was significantly increased in patients with TPP compared with pure hyperthyroidism patients. The levels of thyroid hormone, sex hormone, and insulin were different in Chinese male patients with TPP compared to those with only hyperthyroidism.

Wuling Capsule promotes hippocampal neurogenesis by improving expression of connexin 43 in rats exposed to chronic unpredictable mild stress / 中西医结合学报

Objective: To investigate the effects of Wuling Capsule, a compound traditional Chinese herbal medicine, on hippocampal neurogenesis by examining the expressions of brain-derived neurotrophic factor (BDNF) and connexin 43 (Cx43) in rats with depression induced by chronic unpredictable mild stress (CMS), and thereby to explore its antidepressant mechanism. Methods: Forty-five adult male Sprague-Dawley rats were randomly divided into three groups: control group (n=15), untreated group (n=15) and Wuling group (n=15). All rats except those in the control group were subjected to 3-week CMS to induce depression. At the same time Wuling Capsule was daily added to the diet of the rats in the Wuling group at a dose of 100 mg/kg body weight for 21 days. The degree of depression was determined by sucrose preference test. BDNF expression and neurogenesis were tested by using immunohistochemical staining with BDNF and 5-bromodeoxyuridine (BrdU) antibodies; and the mRNA and protein expression levels of Cx43 in hippocampus were examined by semi-quantitative reverse transcription-polymerase chain reaction and Western blotting. Results: The numbers of BDNF-positive neurons and BrdU-positive particles in dentate gyrus (DG) were significantly decreased in CMS rats as compared with the normal rats, and the same changes were found in Cx43 mRNA and protein expressions. After Wuling Capsule treatment, the depressed behaviors were improved. Moreover, the reduced expression levels of Cx43 mRNA and protein and fewer newborn neurons induced by CMS were recovered to the normal levels. However, BDNF-positive cells remained low in DG. Conclusion: Wuling Capsule can improve the low hippocampal neurogenesis in rats subjected to CMS and the antidepressant effects are related to enhancing the Cx43 expression but not through BDNF mediation.

Effects of cyclosporine A on the expressions of MMP-2 and MMP-9 in the heart of streptozocin-induced diabetic rats / 中华内分泌代谢杂志

The effects of cyclosporine A on matrix metalloproteinases(MMP)-2 and-9 expressions in the cardiac muscle of streptozocin-induced diabetic rats were investigated.The expressions of MMP-2 and MMP-9 mRNA and proteins in the cardiac muscle of diabetic rats were significantly upregulated,which could be decreasedby cyclosporine A(P＜0.05 or P＜0.01).The results suggest that cyclosporine A may effectively ameliorate the injuries of diabetic cardiomyopathy.

The effects of cyclosporine A on immunoglobulins deposition in retina of streptozotocin-induced diabetic rats / 中华内科杂志

Objective To study the autoimmune injuries on diabetic retinopathy(DR)and the protective effects of immunosuppre8sive therapy with eyelosporine A(CsA) on the DR of streptozotocin(STZ)-induced diabetic rats.Methods STZ-induced diabetic rats were randomly divided into 3 groups: group 1:diabetic group without any treatment;group 2:insulin-treated group;group 3:CsA-treated group which was further divided into 2 subgroups:subgroup A:CsA was given 1 week before hyperglycemia appeared and subgroup B:CsA was given one week after hyperglycemia appeared.Subgroup A and subgroup B were further subdivided into 3 groups respectively,based on the dose of CsA(1,4 and 8 mg·kg-1·d-1).As a control group,normal rats were also simultaneously monitored.The pathologic changes in the retina were investigated with HE stain and the deposition of immunoglobulins was detected with immunohistochemistry and immunofluorescent microscopy.Results After 8 week,the deposition of IgG, IgA and IgM was quite significant in the retina of diabetic rats.The data also suggested that insulin treatment had no effects on the DR.In contrast,with CsA intervention,the deposition of immunoglobulins on the retina of diabetic rats vanished.Conclusions Autoimmune injuries were shown,in the present study,to play a critical role in the pathogenesis of diabetic retinopathy.Immunosuppressive treatment with CsA showed protective effects by inhibiting the deposition of immunoglobulins in the retina of diabetic rats.

Detection of the RET proto-oncogene in a family with multiple endocrine neoplasia type 2A syndrome / 中华内分泌代谢杂志

Objective To detect mutations of the RET proto-oncogene in a family with multiple endocrine neoplasia type 2A (MEN2A). Methods Nineteen family members were recruited in the study. The phenotype of the members with MEN2A were observed. PCR was performed to amplify exans 10 and 11 of the RET proto-oncogene. The PCR products were purified and a direct DNA sequence analysis was performed. Results The Cys (TGC)634Arg(CGC) missense mutation and Gly( GGT)691Ser(AGT) in exon 11 of the RET proto-oncogene were both detected in four members of the family. Only the pelymorphism Gly691Ser in exon 11 of the RET proto-oncogene was detected in one member. The results of the ultrasound examination were shown as follows: two members with bilateral thyroid, one side of parathyroid and adrenal solid lesions; one member with bilateral thyroid and one side of adrenal solid lesions; one member with bilateral thyroid and adrenal and one side of parathyroid solid lesions; and one member with multiple thyroid small nodules. Additionally, another three members with abnormal findings on ultrasound examinations had no gene mutation. Conclusion Analysis of RET gene identifies a TGC to CGC mutation at codan 634 and the polymorphism Gly691 Set in exon 11 in this family with MEN2A. Direct DNA sequencing analysis is useful in diagnosis of MEN2A at gene level.