Immune Heterogeneity and Epistasis Explain Punctuated Evolution of SARS-CoV-2

Identifying drivers of viral diversity is key to understanding the evolutionary as well as epidemiological dynamics of the COVID-19 pandemic. Using rich viral genomic data sets, we show that periods of steadily rising diversity have been punctuated by sudden, enormous increases followed by similarly abrupt collapses of diversity. We introduce a mechanistic model of saltational evolution with epistasis and demonstrate that these features parsimoniously account for the observed temporal dynamics of inter-genomic diversity. Our results provide support for recent proposals that saltational evolution may be a signature feature of SARS-CoV-2, allowing the pathogen to more readily evolve highly transmissible variants. These findings lend theoretical support to a heightened awareness of biological contexts where increased diversification may occur. They also underline the power of pathogen genomics and other surveillance streams in clarifying the phylodynamics of emerging and endemic infections. In public health terms, our results further underline the importance of equitable distribution of up-to-date vaccines.

Surgical outcomes in survivors of childhood cancer undergoing thyroidectomy: A single-institution experience.

BACKGROUND: Childhood cancer survivors (CCS) are at increased risk for thyroid disease, and many require definitive management with thyroid surgery. Despite this, there is limited evidence on surgical outcomes among CCS. We sought to evaluate postoperative outcomes at our institution among CCS undergoing thyroid surgery compared to patients without a history of primary childhood malignancy. PROCEDURE: Medical records were reviewed for 638 patients treated at the Children's Hospital of Philadelphia Pediatric Thyroid Center between 2009 and 2020. Rates of surgical complications, including recurrent laryngeal nerve (RLN) paralysis and hypoparathyroidism, among CCS were compared to patients with sporadic/familial thyroid cancer, Graves' disease, and other benign thyroid conditions. Operative time and intraoperative parathyroid hormone levels were also evaluated. RESULTS: There were no significant differences in long-term surgical complication rates, such as permanent RLN paralysis and hypoparathyroidism, between CCS and patients without a history of primary childhood malignancy (all p > .05). For all surgical outcomes, there were no significant differences in complication rates when CCS were compared to those undergoing surgery for sporadic/familial thyroid cancer or Graves' disease (all p > .05). CCS with benign final pathology had significantly higher rates of transient hypoparathyroidism compared to patients with benign thyroid conditions (p < .001). CONCLUSIONS: Our study suggests that CCS are not at higher risk of long-term complications from thyroid surgery when treated by high-volume surgeons within a multidisciplinary team.

Evaluation of Standardized Usage of Oral Antidiabetic Agents in Inpatients' Prescriptions / 中国药师

Objective:To evaluate the standardized usage of oral antidiabetic agents in inpatients to provide reference for the pre -scription standardization .Methods:A retrospective study was used to evaluate the prescriptions of oral antidiabetic agents in inpatients during January and March in 2017 , and statistical analysis was conducted on drug usage and standardization evaluation .Results:There were 886 medication plans including 4,397 prescriptions, which involved in 13 kinds of antidiabetic agents .Metformin and acarbose a-gents were used most frequently .The non-standardization rate was 70.54％with 66.03％unlabeled accurate time for oral administra-tion and 4.51％ labeled wrong time for oral administration .Twelve antidiabetic agents existed non-standardized applications ( >50％) .Conclusion:The main problem in the non-standardized usage of antidiabetic agents is leaving the special time for oral adminis -tration of antidiabetic agents out of account , which not only affect the best efficacy , but also reduce patients ' compliance .It' s neces-sary to standardize the prescriptions of antidiabetic agents to improve the standardization of medication therapy .

Clinical Observation of Treating PHN by Dorsal Root Ganglia Radio Frequency Combined Ozone / 医学研究杂志

Objective To compare the curative effect of treating postherpetic neuralgia (PHN) by dorsal root ganglia pulsed radiofrequency combined ozone and simple dorsal root ganglia pulsed radiofrequency.Methods 68 cases of chest and back PHN patients in accordance with incorporation standard were randomly divided into two groups:control group (n =34) received dorsal root ganglia pulsed radiofrequency while experimental group (n =34) received dorsal root ganglia pulsed radiofrequency combined ozone.The visnal analogue scale (VAS) of two groups before treatment,and 1,3,7 days,1,3 and 6 months after treatment was observed and compared;the clinical treatment effect was evaluated.Results VAS of two groups after treatment all declined obviously compared with that before treatment (P =0.000).Compared with control group,the VAS of experimental group 1 and 3 days after treatment was not significantly different (P＞ 0.05).However,the VAS 7 days,1 and 3 months after treatment declined obviously (P ＜ 0.05).The obvious effect rate of experimental group was higher than control group,so the difference was statistically different (P ＜ 0.05).Patients in both of the groups obtained satisfying curative effect,among which the effective rates of control group and experimental group were 85.29％ and 91.18％ separately.The difference was not statistically different (P ＜ 0.05).But the obvious effect rate of experimental group (70.59％) was higher than control group (38.24％),and the difference was statistically different (P ＜ 0.05).Conclusion Both dorsal root ganglia pulsed radiofrequency combined ozone and simple dorsal root ganglia pulsed radiofrequency generate effect in treating postherpetic neuralgia.But the curative effect of dorsal root ganglia pulsed radiofrequency combined ozone is superior to simple dorsal root ganglia pulsed radiofrequency within medium and long term;therefore,it is a safe and effective treatment.

Clinical Observation of Treating PHN by Dorsal Root Ganglia Radio Frequency Combined Ozone / 医学研究杂志

Objective To compare the curative effect of treating postherpetic neuralgia (PHN) by dorsal root ganglia pulsed radiofrequency combined ozone and simple dorsal root ganglia pulsed radiofrequency.Methods 68 cases of chest and back PHN patients in accordance with incorporation standard were randomly divided into two groups:control group (n =34) received dorsal root ganglia pulsed radiofrequency while experimental group (n =34) received dorsal root ganglia pulsed radiofrequency combined ozone.The visnal analogue scale (VAS) of two groups before treatment,and 1,3,7 days,1,3 and 6 months after treatment was observed and compared;the clinical treatment effect was evaluated.Results VAS of two groups after treatment all declined obviously compared with that before treatment (P =0.000).Compared with control group,the VAS of experimental group 1 and 3 days after treatment was not significantly different (P＞ 0.05).However,the VAS 7 days,1 and 3 months after treatment declined obviously (P ＜ 0.05).The obvious effect rate of experimental group was higher than control group,so the difference was statistically different (P ＜ 0.05).Patients in both of the groups obtained satisfying curative effect,among which the effective rates of control group and experimental group were 85.29％ and 91.18％ separately.The difference was not statistically different (P ＜ 0.05).But the obvious effect rate of experimental group (70.59％) was higher than control group (38.24％),and the difference was statistically different (P ＜ 0.05).Conclusion Both dorsal root ganglia pulsed radiofrequency combined ozone and simple dorsal root ganglia pulsed radiofrequency generate effect in treating postherpetic neuralgia.But the curative effect of dorsal root ganglia pulsed radiofrequency combined ozone is superior to simple dorsal root ganglia pulsed radiofrequency within medium and long term;therefore,it is a safe and effective treatment.

Whole Chromosome 7 Gain Predicts Higher Risk of Recurrence in Pediatric Pilocytic Astrocytomas Independently From KIAA1549-BRAF Fusion Status.

The most frequent genetic alteration identified in pediatric pilocytic astrocytomas and pilomyxoid variant is the KIAA1549-BRAF fusion, which typically results from a 2.0 Mb tandem duplication in chromosome band 7q34. Less frequent abnormalities include fusion genes,BRAF, FGFR, KRAS, and NF1 point mutations, and whole chromosome gains. To correlate genetic alterations with clinical course data, we retrospectively analyzed the tumors with pilocytic and pilomyxoid histology of a cohort of 116 pediatric patients, aged 5 months to 23 years. Gross total resection was associated with a decreased risk of recurrence (p = 0.001), supporting previous findings that complete tumor excision correlates with long-term and disease-free survival. We found no significant association between recurrence rate and the presence of the KIAA1549-BRAF fusion or BRAF mutation (p = 0.167). Interestingly, gain of whole chromosome 7 (WC7) was associated with a 4.7-fold increased risk of tumor recurrence, even after adjusting for surgical status (p = 0.025), and other genetic alterations. Using fluorescence in situ hybridization, we demonstrated that when WC7 gain accompanies the KIAA1549-BRAF fusion, the fusion likely arises first. This study highlights the utility of genetic studies for risk assessment of pilocytic and pilomyxoid astrocytomas, which may impact treatment selections.

Pathological changes of nasal mucosa after instillation of 37℃ normal saline in rats / 中国耳鼻咽喉头颈外科

[ABSTRACT]OBJECTIVE To obser ve t he pathological changes of nasal mucosa in rats after instillation of 37℃ normal saline. METHODS Forty-eight qualified rats were given instillation of 37℃ nomal saline 30 times, once per minute. Another 2 qualified rats served as control. After instillation, in the 15, 30 minutes and 1st, 3rd, 7th, 14th, 42th, 28th day respectively, the nasal septum mucosa of 6 rats was observed by light and electron microscopy. The corresponding area of the mucosa of control group was also observed by light and electron microscope. RESULTS Under light microscope, the arrangement of cell was disordered in the 1st, 3rd, 7th days. But there is no damage of vascular gland structure. After 14 days, the disorder recovered. With electron microscope, edema of cells, expansion of perinuclear gap, disorder of cilia and microwilli was found in the 30 minutes, 1st, 3rd day. All these began recover in the 7th days, and completely restored in the 28th day. CONCLUSION 37℃ nomal saline drip can damage nasal mucosa, but the damage is light, which is characterized by disorder and shortage of cilia and microvilli, edema of the epithelial cells. And the damage can recover quickly. It began in the 30 minutes after instillation, reached its peak in the 3rd day. And the recovery began in the 7th day, and completed in the 28 day.

Analysis of the related risk factors for neuropathic pain in diabetic rats / 中国糖尿病杂志

Objective To explore the related risk factors for neuropathic pain in diabetic rats.Methods Female Wistar rats of clean grade were divided into three groups :Non diabetic standard diet (NdStd) group (n=10) ,diabetic high fat diet and pain (DbHFP) group (n=10) ,and diabetic high fat diet and no pain (DbHFNP) group (n=10).Body weight ,blood glucose ,TG ,TC ,HDL‐C ,LDL‐C and 50%pain threshold were measured regularly to assess the relationship between blood lipids and pain. Results Non‐conditional logistic regression analysis showed that pain threshold was negatively correlated with TG , LDL‐C and blood glucose(P 0.05). Conclusion Pain threshold of diabetic rats was negatively correlated with TG ,LDL‐C and blood glucose ,and positively correlated with HDL‐C.

Effect of mlodipine/hydrochlorothiazide in patients with essential hypertension：A systematic review / 重庆医学

Objective To systematically evaluate the efficacy and safety of amlodipine (A)/hydrochlorothiazide(H) versus val‐sartan(V)/hydrochlorothiazide(H) in treatment of essential hypertension .Methods Literature was retrieved online in Cochrane Li‐brary ,PubMed ,OVID ,MEDLINE ,EMBASE ,CBM ,CNKI ,VIP and Wan fang database up to November 2013 .Relevant magazines were retrieved manually .Quality of the included studies was assessed and Meta‐analysis was performed with RevMan 5 .2 software . Results Seven randomized controlled trials(RCTs) were finally included .Meta‐analyses showed that :in terms of lowering ABP ,V/H group was more effective than A/H group ,the difference was statistically significant (P0 .05) .Ad‐verse events occurred less frequently with V/H group compared with A/H group ,the difference was statistically significant (P<0 .05) .Conclusion A/H treatment of essential hypertension is inferior to V/H ,and has more adverse events .

Analysis on effect of small group learning in the course of introduction to general practice / 中华医学教育探索杂志

Objective To introduce small group learning in the course of introduction to gen-eral practice to cultivate students' ability of active learning and innovation. Methods Totally 221 students of 2008 grade A and B classes were enrolled as teaching objects and were divided into 20 groups. Introduction to general practice was used as learning materials. One week before the class, teacher gave students learning task and A and B classes carried on class discussion respectively. Re-view speaking was conducted by the representatives of groups. Effectiveness was evaluated through the observation,interview,questionnaire survey and answer scoring points. Results Overall support per-centage to small group learning was 91%. Percentages of students who believed that small group learn-ing was beneficial to cultivating the ability of active learning and innovation were 88% and 73% re-spectively. Conclusions Introducing small group learning in the course of introduction to general practice is effective and conductive to training students' ability to study and innovate.

Perioperative analgesia in total knee replacement:multimodal analgesia schemes and optimal pain management / 中国组织工程研究

BACKGROUND:Positive treatment of perioperative analgesia after total knee arthroplasty can accelerate recovery of joint function, reduce complications after replacement, and improve overal technical evaluation of total knee arthroplasty. ＜br> OBJECTIVE:To summarize commonly used analgesic drugs and analgesia method of total knee arthroplasty. ＜br> METHODS:A computer-based online research of Wanfang database and PubMed database was performed to col ect articles published between 1994 and 2014 with the keywords of“total knee replacement, epidural analgesia, peripheral nerve block, joint local analgesia, patient control ed analgesia, cold treatment”in Chinese and English. ＜br> RESULTS AND CONCLUSION:There were 986 articles after the initial survey. Final y, 55 articles were included according to the inclusion and exclusion criteria. As the technology for total knee arthroplasty, early functional rehabilitation and replacement of pain control has been widely concerned, a large number of literatures about analgesic drugs and analgesic programs emerge. Analgesic drugs include opioids, non-steroidal anti-inflammatory drugs, local anesthetics and N-methyl-aspartate receptor blockers. Analgesic program includes epidural analgesia, peripheral nerve blockage, joint local analgesia, patient-control ed analgesia and cold therapy. These analgesic drugs and methods have their advantages and disadvantages. At present, multimodal analgesia schemes have been recognized, but the optimal pain management scheme remains controversial. Increasing considerations should be paid on the choice of analgesic methods, depending on individual characteristics and existing technology.

Three cases of nasal sinus foreign body caused by debris flow / 临床耳鼻咽喉头颈外科杂志

A retrospective analysis of 3 patients with nasal sinus foreign body caused by debris flow admitted to our department. All of the three patients showed foreign odor and mucopurulent discharge in nasal cavity after the debris flow blast injury. CT examination found high density soft tissue shadow or calcification in the nasal sinus. All the diagnoses were nasal sinus foreign body in three patients. The nasal sinus foreign bodies was dislodged through endoscopic sinus surgery. Three patients are all well-healed.

Usefulness of determining a protein induced by vitamin K absence in detection of hepatocellular carcinoma / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Protein induced by vitamin K absence or antagonist II (PIVKA II), also called des-gamma carboxy prothrombin (DCP), is a sensitive marker for the diagnosis of hepatocellular carcinoma (HCC), in Japan and the United States since the sensitive kits were available (1998). PIVKA II is not used in clinical diagnosis in China so far. The aim of this study was to assess the diagnostic value of PIVKA II in Chinese patients with HCC.</p><p><b>METHODS</b>Serum PIVKA II and alpha-fetoprotein (AFP) levels were determined in 60 patients with HCC and 30 patients with cirrhosis not carrying HCC.</p><p><b>RESULTS</b>The mean serum concentration of PIVKA II in HCC patients (784.3 +/- 1364.1 mean +/- s) was higher than that in cirrhosis patients (16.1 +/- 31.7); this difference was highly significant (P < 0.0001). When the cutoff level of 40 mAU/ml was used as the level of discriminating HCC from cirrhosis, 51.7% of patients (31/60) with HCC had PIVKA II values above this level (sensitivity). Only 4 patients with cirrhosis had such high PIVKA II levels. Thus, the specificity of this test was 86.7% (26/30). Total accuracy was 62.2% [(31 + 26)/(60 + 30)]. Seven of 19 small HCCs (36.84%) had PIVKA II values above the cutoff level. Concentrations of AFP above 20 ng/ml were observed in 34 of 60 patients with HCC (56.7%) and in 11 patients with cirrhosis (36.7%). Eleven of 26 patients with HCC (46.2%) without increased AFP had concentrations of PIVKA II greater than 40 mAU/ml. No significant correlation was found between serum levels of AFP and PIVKA II that were measured in 60 HCC patients (rs = 0.101, P = 0.247). Combining the information from PIVKA II and AFP showed an increase of approximately 21.6% over AFP and 26.7% over PIVKA II alone. For small HCC patients, combining the information from PIVKA II and AFP showed an increase of approximately 15.8% over AFP alone and 21.1% over PIVKA II alone.</p><p><b>CONCLUSION</b>PIVKA II is a useful early diagnostic marker for HCC and may be more sensitive when combined with AFP in Chinese patients.</p>

Evaluation of different factors involved in volume treatment of hypovolemic shock / 中华麻醉学杂志

time of infusion. Data analysis indicated that A1B3C2 was the best combination of the 3 factors according to the degree of lung injury. Conclusion Adequate amount of HES 200/0.5 infused during compensated stage of hypovolemic shock produces best result.

The changes in blood electrolytes and blood gases during anaphylactic shock induced by Echinococcus granulosus in sheep / 中华麻醉学杂志

Objective To access the changes in blood gases and electrolytes during anaphylactic shock induced by Echinococcus granulosus (EG) in sheep.Methods Fifteen healthy sheep of either sex weighing 31.2 ? 3.5 kg were repeatedly infected with EG for six months. The infected sheep were anesthetized with intramuscular thiopental 20mg?kg-1 and ketamine 15 mg?kg-1. The animals were breathing spontaneously and placed on the left side. ECG (lead Ⅱ) was monitored. Swan-Ganz catheter was placed via right internal jugular vein for hemodynamic monitoring. Anaphylactic shock was induced with antigen prepared from fluid in EG capsules. Blood samples were taken from right internal carotid artery before shock (T0) and 3.5 min (T1 ), 8 min (T2), 15 min (T3), 30 min (T4) and 60 min (T5 ) after shock was induced for determination of blood Na+ , K+ , Hct, Hb, pH, PaO2 , PaGO2 and HCO3-. Shock was confirmed by hypotension (MAP decreased by 30%), tachypnea, dyspnea, agitation and pupil dilation. Results Three sheep did not develop shock and two sheep died of severe shock within 10 min after iv antigen challenge. Blood K+ significantly increased at T1 and T2 after antigen challenge and then gradually returned to baseline value at T5 . PaO2 decreased, PaGO2 increased and pH deceased after challenge. Hct and Hb also increased significantly after challenge. Conclusion There are significant changes in blood gas and electrolytes indicated by hyperkalemia, acidosis and hypoxemia during anaphylactic shock induced by EG.