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Pruritus is one of the typical clinical manifestations of bullous pemphigoid (BP) . In recent years, researchers have gradually recognized that the histamine-independent itch pathway plays an important role in BP. Eosinophils, basophils, interleukin (IL) -31, IL-4, IL-13, thymic stromal lymphopoietin, periostin and substance P are all closely related to the occurrence of pruritus in BP. This review mainly elaborates research progress in mechanisms related to pruritus in BP.
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Objective:To discover the effective terpenoids in Xinjiang <italic>Pleurotus ferulae</italic> with the activity of anti-esophageal carcinoma. Method:By screening the activity of human esophageal cancer Eca109 cells， the ethyl acetate extract phase of <italic>P. ferulae </italic>ethanol extract （PFEP-E） was separated and purified by silica gel chromatography and preparative thin layer chromatography. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q/TOF-MS） combined with online network databases such as Metlin， MassBank， PubChem and related literature were used to identify the effective elution sites and analyze their contents. Result:The elution fraction （Fr<sub>2-3∶1</sub>） of petroleum ether-ethyl acetate （3∶1） on the silica gel column had the strongest inhibitory activity on the proliferation of human esophageal cancer Eca109 cells. The component analysis showed that 24 effective terpenoids were identified under positive ion mode， and 28 effective terpenoids were identified under negative ion mode， a total of 52 terpenoids were identified， which were isolated from this edible fungus for the first time. Content of total terpenoids in Fr<sub>2-3∶1</sub> were 62.88 mg·g<sup>-1</sup>， including 2 monoterpenoids， 5 sesquiterpenoids， 15 diterpenoids and 30 triterpenoids， accounting for 1.32%， 12.04%， 47.55%， 39.09% of the total terpenoids， respectively. Diterpenoids and triterpenoids were the main components of the effective terpenoids in <italic>P. ferulae</italic>， accounting for 86.64% of the total terpenoids. Gibberellins were the main diterpenoids， accounting for 79.70% of the total diterpenoids， triterpenoids were mainly ganoderic acids， accounting for 29.25% of the total triterpenoids. The results of methyl thiazolyl tetrazolium （MTT） test showed that gibberellin A<sub>3</sub> and gibberellin A<sub>5</sub> had weak anti-esophageal cancer activity， while gypsogenin and oleanolic acid had strong anti-esophageal cancer activity. Conclusion:The effective terpenoids of <italic>P. ferulae</italic> against esophageal cancer are triterpenoids mainly composed of ganoderic acids， which can provide theoretical basis for the development of terpenoids of <italic>P. ferulae</italic> as anti-tumor drugs and the development of functional foods， and help to effectively improve the additional output value of <italic>P. ferulae</italic>.
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Objective:To compare the effect of one stage laparoscopic surgery and conservative treatment for periappendiceal abscess.Methods:From Jun 2013 to Jun 2020 116 patients with periappendiceal abscess were evenly divided into one stage appendectomy group and conservative treatment group . Clincal results were compared between the two groups .Results:The use of antibiotics in one stage operation group was shorter than that in the conservative group[5(4-6) d vs. 7(6-8)d , Z=-7.227, P=0.000], time to normal temperature was shorter[3(2-3) d vs. 5(4-5)d , Z=-7.809, P=0.000], Leukocyte count return to normal was quicker[4(3-5)d vs. 6(5-7) d , Z=-7.346, P=0.000], hospital stay was shorter[8(7-9) d vs. 14(13-15) d , Z=-9.293, P=0.000], hospital ecperss were less[8 848(8 434-9 073) yuan vs. 14 003(12 999-14 894) yuan, Z=-9.127, P=0.000], the rate of recurrent or residual abscess (7% vs.29%, χ 2=9.827, P=0.002) was lower, while effective rate was higher (93% vs. 79%, χ 2=4.640, P=0.031). Conclusion:One stage laparoscopic appendectomy for the treatment of periappendiceal abscess is safe and more economic , effective method.
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Objective:To evaluate lung protection of remote limb ischemic preconditioning after pulmonary resection.Methods:Methods sixty adult patients scheduled for elective pulmonary resection, were randomly divided into control group(group C, 30 cases) and remote limb ischemic preconditioning(group RLIP, 30 cases) using a random number table. Before one-lung-ventilation(T0), at 30 minites, 1 hour and 2 hours of OLV(T1, 2, 3), 15minites after re-expansion of the collapsed lung(T4), blood samples were drawn from the radial artery and vein for blood gas analysis, alveolar-arterial oxygen gradient(A-aDO 2)、pulmonary shunt ratio(Qs/Qt)were calculated. Extraction time of closed thoracic drainage tube, length of hospital stay, the incidence of in-hospital complications after operation were recorded. Results:Compared to T0 , each group at T1-T4, A-aDO 2 were obviously increased. We found that at T3, A-aDO 2 of group C increased much more higher and statistically significant( P<0.05). Compared to group RLIP, Qs /Qt of group C were significantly increased at T2( P<0.05). Compared with C group, the expression of microtubule-associated protein 1 light chain 3B in lung tissues was significantly"up-regulated in RLIP group( P<0.05). Followed the extraction time of closed thoracic drainage tube, length of hospital stay, the incidence of in-hospital complications after operation there were no statistically different( P>0.05). Conclusion:Remote limb ischemic preconditioning had some protective effect after pulmonary resection, which mechanism may be related to enhancing autophagy in the operated 1ung tissues of the patients.
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Objective To analyze the clinicopathological features and prognostic factors of common subtypes of non-transparent renal cell carcinoma.Methods Retrospective analysis of 115 patients with pathologically confirmed non-transparent renal cell carcinoma from January 2003 to December 2017,including 67 males and 48 females,with a male to female ratio of 1.4∶ 1.The average age is (51.2 ± 13.4)years old.71 cases were asymptomatic renal cancer,44 cases had clinical symptoms,including 10 cases of gross hematuria,28 cases of low back pain,4 cases of hematuria with low back pain,and 2 cases of abdominal mass.There were 49 open surgery and 66 laparoscopic surgery.58 patients underwent radical nephrectomy and 57 underwent partial nephrectomy.Of the 115 patients,17 (14.9％) had abnormal hemoglobin (Hb),22 (19.1％) had abnormal platelet (PLT) count,18 (15.7％) had abnormal alkaline phosphatase,and abnormal lactate dehydrogenase 16 cases (13.9％).The Kaplan-Meier survival analysis method was used to calculate the survival rate of patients,and the Cox proportional regression risk model was used to analyze the prognostic factors.Results The postoperative pathological stage was 57 cases in T1a stage,38 cases in T1b stage,12 cases in T2a stage,8 cases in T2b stage,2 cases of regional lymph node positive,and 113 cases negative;no distant metastasis.Pathological types:42 cases of renal chromophobe cell carcinoma,37 cases of papillary renal cell carcinoma type Ⅰ,36 cases of type Ⅱ.The average follow-up time was 38.6 months,and the rate of loss of follow-up was 3.5％ (4/115).The 1,3,and 5 year overall survival rates of 115 patients with common subtypes of non-transparent renal cell carcinoma were 99.1％,95.8％,and 81.1％,respectively.Multivariate Cox regression analysis found that the pathological type (OR =4.625,P =0.014),four indicators ≥ 3 abnormalities (OR =30.853,P =0.024),lymph node metastasis (OR =35.663,P =0.006) were the group.An independent factor in the survival time of patients with common subtypes of non-transparent renal cell carcinoma.Conclusions Compared with papillary renal cell carcinoma type Ⅰ and renal chromophobe cell carcinoma,papillary renal cell carcinoma type Ⅱ has a higher degree of malignancy and a poor prognosis.The pathological types of the common subtypes of nontransparent renal cell carcinoma,four indicators (Hb,PLT count,alkaline phosphatase,and lactate dehydrogenase) ≥3 abnormalities and lymph node metastasis are independent prognostic factors for overall survival.
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OBJECTIVE@#To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis.@*METHODS@#Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ⪖ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ⪖ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis.@*RESULTS@#The serum lysophosphatidylglycerol level was significantly higher in the group with ⪖ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ⪖ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ⪖ 71% and the group with sputum neutrophils < 71%.@*CONCLUSION@#Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.
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Adult , Female , Humans , Male , Middle Aged , Asthma , Blood , Allergy and Immunology , Eosinophils , Allergy and Immunology , Glycerophospholipids , Blood , Metabolomics , Neutrophils , Allergy and Immunology , Sputum , Cell Biology , Allergy and ImmunologyABSTRACT
BACKGROUND: Repair of bone defects is not only a clinical problem, but also a hot topic in the field of orthopedics. Although autologous bone grafting is considered as the "gold standard" for bone repair, its use is limited due to the limited source of autogenous bone, bone infections and pains that are easy to occur in the donor region. Allograft bones are always associated with immune rejection, slow healing, and infection. Therefore, it is imminent to develop new materials for bone repair. OBJECTIVE: To explore the effect of rabbit adipose-derived stem cells (rADSCs) as seed cells and hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) composite as a carrier on the repair of rabbit vertebral defects. METHODS:Thirty-eight 3-month-old New Zealand white rabbits were selected,and two of them were used to culture rADSCs in vitro. Passage 3 rADSCc were inoculated on HA/β-TCP scaffolds and then cultured in vitro for 2 weeks.A 5 mm×5 mm×3 mm bone defect was prepared at the anterior edge of L4/5vertebral body in the remaining 36 rabbits. These model rabbits were then randomized into cell-scaffold composite group, scaffold group and control group with no intervention, with 12 rabbits in each group. rADSCs/HA/β-TCP composite and HA/β-TCP scaffold were implanted into the cell-scaffold and HA/β-TCP groups, respectively. Anteroposterior and lateral DR of the spine and Lane-Sandhu X-ray were performed at 4, 8, 12 postoperative weeks. All rabbits were sacrificed at 12 postoperative weeks and specimens were collected for gross and histopathological observations. RESULTS AND CONCLUSION: Under the gross observation, bone defects in the cell-scaffold group were essentially replaced by new bone tissues, which was significantly better than that in the scaffold group and control group. At 12 postoperative weeks, the material implanted was basically absorbed in the cell-scaffold group, partially absorbed in the scaffold group and poorly absorbed in the control group in which there was a clear boundary with the surrounding tissues and patchy calcified shadows were visible. X-ray results showed that the repair effect in the cell-scaffold group was better than that in the scaffold group and control group (P < 0.05). Histopathological findings showed the marked absorption of the implant in the cell-scaffold group, partial residual in the scaffold group with some fibrous calluses and osteoid tissues, and a large amount of fiber tissues and a small amount of calluses in the control group. Overall, the rADSCs/HA/β-TCA has a good ability to repair bone defects.
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Objective To study the serum metabonomic changes in abnormal Savda rat model of type 2 diabetes mellitus (T2DM).Methods Sprague Dawley (SD) rats were subjected to abnormal Savda-producing conditions followed by induction of T2DM.Plasma samples were collected from each test group and analyzed by 1H nuclear magnetic resonance (NMR) spectroscopy.The spectral profiles were analyzed by multivariate analysis using orthogonal projection to latent structurs discriminant analysis (OPLS-DA).Results The content of glucose and lactic acid in plasma of the rats with abnormal Savda syndrome was decreased, while the contents of VLDL, LDL and carnitine increased obviously.For abnormal Savda rat model with T2DM, the concentration of amino acids (alanine, valine, isoleucine, leucine, tyrosine, glutamic acid, phenylalanine, methyl-histidine, glycine), and lactic acid, pyruvic acid, glycoprotein, citric acid, creatinine, β-hydroxybutyric acid, acetoacetic acid, acetic acid, acetate, creatine, carnitine, scyllo-inositol, VLDL, LDL were decreased, and glucose and taurine concentrations were increased significantly.Conclusions Protein metabolism, phenylalanine and tyrosine metabolic pathway, glycolytic pathway and the lipid metabolic pathway may be considered as biomarkers of abnormal Savda rat model of T2DM.
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The paper analyzes the status of trauma rescue and treatment informatization in Xinjiang,states the thoughts of construction of intelligent trauma medical center in southern Xinjiang (including the telemedicine system based on regional medical network,orthopedics trauma and disease diagnosis and treatment platform,etc.).It also provides the application examples and discusses the social economic benefits.
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Objective To explore the epidemic situation of animal plague in Junggar Basin natural plague foci.Methods Data on epidemics of plague and on population involved,as well as results on antibodies and pathogens,were analyzed.Samples on animals and vectors were collected from 18 counties in Junggar Basin plague natural foci between 2007 and 2016.Results The density of Rhombomys (R.) opimus was temporally fluctuant,from 2.1/hm2 to 22.6/hm2 respectively.However,the spatial distribution appeared asymmetrical,with the highest seen in Kelamayi and Wumuqimidong counties,as 14.2/hm2 and 13.0/hrn2 respectively.Rates of capture on nocturnal rodents were from 4.2％ to 10.1％,with the highest rate as 10.1％ in 2014.Meriones meridianus appeared the dominant species in the nocturnal community of rodents,which accounted for 81.9％.Regarding the spatial and temporal distributions,rates ofR.opimus with fleas appeared fluctuant,with an average rate as 90.7％ and the average total flea index was 10.44.In flea community of R.opimus,Xenopsylla (X.)skrjabini was found the dominant species,popular in distribution and accounted for 47.8％.The average rate of nocturnal rodents with flea was 20.2％,with total flea index as 1.20 and the dominant fleas were X.conformis conformis and Nosopsyllus laeviceps.A total of 13 species with 9 087 serum samples from rodents were detected as having Y.pestis antibody by IHA,with 617 positive samples.Of them,the positive rate of having R.opimus appeared the highest (9.4％),followed by D.sagitta (1.1％).Spatially,two clustered areas were found,with one in the eastern Junggar Basin from Changji to Mulei county,with the antibody positive rates ofR.opimus as 14.3％.The other one was in the central area of Junggar Basin,including Kelamayi,Shawan and Wusu counties,with the antibody positive rate as 13.6％.The prevalence of plague on R.opimus was fluctuant,with the lowest seen in 2008,with the average antibody positive rate of R.opimus as 1.0％ and the highest as 19.3％ in 2013.A total of 18 strains were isolated from 2007 to 2016.However,most of the strains were isolated from R.opimus and parasitic fleas,accounted for 8/9,in Kelamayi,Wulumuqi-midong and Jimusaer,respectively.Conclusions Complex ecosystem was seen in the Junggar Basin natural plague foci,with the multiple composition of species and different community structure of hosts and vectors,plus the flustering prevalence.Animal plague was seen in the whole region with succession of the plague nature foci.Passive transmission of plague between human beings and animals through close contacts was seen which was driven by economic benefits to some degree.
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Objective To explore the epidemic situation of animal plague in Junggar Basin natural plague foci.Methods Data on epidemics of plague and on population involved,as well as results on antibodies and pathogens,were analyzed.Samples on animals and vectors were collected from 18 counties in Junggar Basin plague natural foci between 2007 and 2016.Results The density of Rhombomys (R.) opimus was temporally fluctuant,from 2.1/hm2 to 22.6/hm2 respectively.However,the spatial distribution appeared asymmetrical,with the highest seen in Kelamayi and Wumuqimidong counties,as 14.2/hm2 and 13.0/hrn2 respectively.Rates of capture on nocturnal rodents were from 4.2％ to 10.1％,with the highest rate as 10.1％ in 2014.Meriones meridianus appeared the dominant species in the nocturnal community of rodents,which accounted for 81.9％.Regarding the spatial and temporal distributions,rates ofR.opimus with fleas appeared fluctuant,with an average rate as 90.7％ and the average total flea index was 10.44.In flea community of R.opimus,Xenopsylla (X.)skrjabini was found the dominant species,popular in distribution and accounted for 47.8％.The average rate of nocturnal rodents with flea was 20.2％,with total flea index as 1.20 and the dominant fleas were X.conformis conformis and Nosopsyllus laeviceps.A total of 13 species with 9 087 serum samples from rodents were detected as having Y.pestis antibody by IHA,with 617 positive samples.Of them,the positive rate of having R.opimus appeared the highest (9.4％),followed by D.sagitta (1.1％).Spatially,two clustered areas were found,with one in the eastern Junggar Basin from Changji to Mulei county,with the antibody positive rates ofR.opimus as 14.3％.The other one was in the central area of Junggar Basin,including Kelamayi,Shawan and Wusu counties,with the antibody positive rate as 13.6％.The prevalence of plague on R.opimus was fluctuant,with the lowest seen in 2008,with the average antibody positive rate of R.opimus as 1.0％ and the highest as 19.3％ in 2013.A total of 18 strains were isolated from 2007 to 2016.However,most of the strains were isolated from R.opimus and parasitic fleas,accounted for 8/9,in Kelamayi,Wulumuqi-midong and Jimusaer,respectively.Conclusions Complex ecosystem was seen in the Junggar Basin natural plague foci,with the multiple composition of species and different community structure of hosts and vectors,plus the flustering prevalence.Animal plague was seen in the whole region with succession of the plague nature foci.Passive transmission of plague between human beings and animals through close contacts was seen which was driven by economic benefits to some degree.
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Objective To discuss the surgical treatment and prognosis of solid pseudo papillary tumor of the pancreas. Methods The clinical data of 45 patients with solid pseudo papillary tumor of the pancreas were analyzed retrospectively. Surgical treatment was performed in all cases,including 11 cases of local excision of the pancreas,20 cases of resection of the pancreatic body and tail,5 cases of resection of the pancreatic body,tail plus spleen,and 9 cases of pancreaticoduodenectomy. Results A total of 43 ca-ses were followed up for 6 ~ 160 months,with an average of(41. 5 ± 1. 5)months. There were 8 cases of dyspepsia,2 cases of pancreatic fistula,2 cases of pleural effusion,2 cases of incision liquefaction and in-fection,and 1 case of early hemorrhage of the digestive tract. All patients were cured by conservative treat-ment. No metastasis,recurrence or death occurred after the operation. Conclusion The pseudo papillary tumor of the pancreas is a potential low grade malignant tumor which mainly appears in females. Surgery is the only radical treatment and its prognosis is generally good.
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BACKGROUND:Recently, subclinical hypothyroidism has been associated with increased carotid intima-media thickness, but it is controversial. OBJECTIVE:To assess whether carotid intima-media thickness in patients with subclinical hypothyroidism differs from that in euthyroid subjects. METHODS:We searched published studies concerning the carotid intima-media thickness of patients with subclinical hypothyroidism in comparison with euthyroid subjects. Then, we evaluated each potential study for eligibility, assessed the methodological quality, and extracted the data for a Meta-analysis. RESULTS:Eight observational studies with 3 602 cases met the eligibility criteria. In patients with subclinical hypothyroidism, the pooled estimate of the weighted mean difference (WMD) of increased carotid intima-media thickness was 0.056 [95%CI (0.020, 0.092)]. Sensitivity analysis using a pooled result of the seven higher-quality studies demonstrated higher carotid intima-media thickness level in patients with subclinical hypothyroidism than in euthyroid subjects [WMD=0.064, 95%CI(0.024, 0.105)]. In a subgroup analysis, subclinical hypothyroidism was even more significantly associated with the carotid intima-media thickness in patients with a mean thyrotropin level > 10.0 mU/L [WMD=0.082, 95%CI (0.049, 0.116)]. Subclinical hypothyroidism was also associated with a significant increase in systolic blood pressure, triglyceride levels, total cholesterol levels, low-density lipoprotein levels and with a decrease in fasting plasma glucose. This meta-analysis indicates that subclinical hypothyroidism is associated with an increased carotid carotid intima-media thickness, which may be due to elevated thyrotropin, dyslipidemia and hypertension. Despite the obvious individual differences, a prospective large-sample study is necessary to further assess the conclusions of this observation.
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Large vestibular aqueduct syndrome (LVAS) is one of common non-syndromic hearing disorders. With the rapid development of medical imaging, audiology, molecular biology, genetics, cochlear implant surgery, we have made remarkable achievements in the diagnosis and treatment of large vestibular aqueduct syndrome. This article reviewed related researches of the large vestibular aqueduct syndrome.
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Humans , Cochlear Implants , Hearing Disorders , Genetics , Vestibular Aqueduct , Congenital Abnormalities , Vestibular Diseases , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To understand the distribution, fauna, population structure of host animals and their parasitic fleas as well as popular dynamic of animal plague of natural plague foci in Junggar Basin.</p><p><b>METHODS</b>Sample materials and data of animals and vector insects were collected using ecological methods and the population structures were analyzed statistically. F1 antibody of Yersinia pestis in rodents' serum and organ suspension was detected by means of IHA while the pathogen of Y. pestis in rodents and vector insects was detected by means of aetiological detections and the isolated Y. pestis was detected using biochemical methods.</p><p><b>RESULTS</b>The small mammals which were found in Junggar Basin belonged to 17 species of 11 genera 7 families. Of them, 13 species of rodents were included whose parasitic fleas belonged to 19 species of 10 genera 8 families. The average coverage of Rhombomys opimus hole-community was 22.5% in Junggar Basin with the average density of R. opimus hole-community was 15.9/hm2 and the average rate of habitat of the hole-community was 70.2%. In the R. opimus community, the average density of rodents was 3.1/hole-community, and 34.4/hm2 in the nature plague foci. In the population structure of the hole-community of R. opimus, R. opimus accounted for 72.9% in the total captured rodents, Meriones meridianus was 24.5% while the others were 2.6%. In the nocturnal community of rodents, M. meridianus accounted for 64.0% in total captured rodents, Dipus sagitta was 15.1%, M. erythrourns was 7.5% and the others were 13.4%. In the rodents community of Junggar Basin, the rate of R. opimus with fleas was 84.9%, which was the highest, followed by M. tamariscinus, Euchoreutes naso and M. erythrourns, with the rates as 71.4%, 66.7% and 62.7% respectively. The rate of M. meridianus with fleas was 38.3%. There were 16 species of parasitic fleas in R. opimus, with the total flea index as 8.58 and the dominant species was Xenopsylla skrjabini. There were 17 and 16 kinds of fleas in M. erythrourns and M. meridianus respectively with the total flea index were 1.59 and 1.15, with dominant fleas were Nosopsyllus laeviceps and X. skrjabini. The serum and organ suspension of 3179 rodents which belonged to 12 species were detected by means of IHA, of them 174 samples were positive and the positive rate was 5.5%. There were 1356 samples of R. opimus in these materials, and 164 were positive, accounted for 12.1%. The samples of M. meridianus were 1255, with 9 positive, accounted for 0.7%. The samples of D. sagitta were 116 with 1 positive and the rate was 0.9%. The samples of other rodents were 452 but were all negative. There were in total 2975 organs collected from rodents, when detected by methods of isolated of Y. pestis. 15 strains of Y. pestis were isolated from 1243 R. opimus, and 2 strains isolated from 1230 M. meridianus. A total number of 11 647 fleas from rodents were detected by methods of isolated of Y. pestis in which 1 strain of Y. pestis was isolated from 4713 X. skrjabini, and 6 were isolated from 2101 Xenopsylla minax, 1 from 328 Xenopsylla conformis conformis and 1 from 250 Echidnophaga oschanini. Among the other 4255 fleas, none was isolated. The biochemical properties of these Y. pestis which isolated from Junggar Basin were positive of Maltose, Ejiao sugar and Glycerol, and negative of Rhamnose and Nitrogen, which were all strongly poisonous to mouse.</p><p><b>CONCLUSION</b>The natural plague foci in Junggar Basin spread all over the whole Junggar Basin. There were animal plague cases found in 12 counties (cites) while Karamy, Bole, Jimusaer and Qitai were confirmed as plague foci counties (cities). Animals and vector insects of the foci were complicated but the ecological system was stable. R. opimus was recognized as the dominant host animal and its biochemical type belonged to the Middle Ages, suggesting that the foci was a new type of natural plague foci.</p>