Advances in the gene therapy of primary hyperoxaluria / 中华泌尿外科杂志

Primary hyperoxaluria (PH) is a rare autosomal recessive hereditary disease, characterized by calcium oxalate kidney stone and nephrocalcinosis caused by defects in enzymes of liver glyoxylate metabolism. Up to now, treatment options for PH are limited. Although medication treatment and liver transplantation can slow down the progression and mitigate the symptoms, the evidence for them turned out to be weak. In recent years, breakthroughs in biotechnology provide novel promising directions for drug development. Small interfering RNA drugs, such as lumasiran and nedosiran, selectively reduce hepatic expression of glycolate oxidase and lactate dehydrogenase respectively, reducing hepatic oxalate production and urinary oxalate levels in PH patients. Gene-editing, such as CRISPR/Cas9, will be a potential treatment method of PH. This review encompasses recent developments in the gene therapy of PH.

Advances of monogenic kidney stone diseases associated with purine metabolism / 中华泌尿外科杂志

Some kidney stones are caused by single gene mutations, and monogenic kidney stone diseases associated with purine metabolic disorder mainly including adenine phosphoribosyltransferase(APRT) deficiency, hypoxanthine-guanine phosphoribosyltransferase(HPRT)deficiency, hereditary xanthinuria(HX), and some diseases caused by gene mutations such as PRS1, SLC22A12, SLC2A9 and ABCG2. Such diseases can lead to abnormal metabolism of purine and uric acid, and then form 2, 8-dihydroxyadenine stones, uric acid stones or xanthine stones. This kind of diseases are rare, the genotype and phenotype of different types of monogenic diseases related to purine metabolism have their own characteristics and are not widely recognized. At present, the main treatment is medical therapy. Gene sequencing will make the diagnosis and find more disease-related genes or mutations. Gene editing, such as CRISPR/Cas9 technology, makes it possible to cure monogenic kidney stone diseases associated with purine metabolism disorder in the future.

How many COVID-19 PCR positive individuals do weexpect to see on the Diamond Princess cruise ship?

The coronavirus disease 2019 (COVID-19) has become a global epidemic crisis with tens of thousands confirmed cases surfacing everyday. The infection rates in households, offices and public places are quite different from those in encompassed spaces such as airplanes, trains and cruise ships. Studying the behavior of COVID-19 in confined spaces like Diamond Princess cruise is of great importance to understand the disease progression and to manage the epidemic. We propose a novel mixture model to estimate the infection distribution and total infected number after 14 days of quarantine based on PCR test data performed on the Diamond Princess cruise. ResultsIn contrast to the officially reported 634 individuals with PCR-positive results after the 14 day quarantine, which as of April 27, 2020 had increased to 712, we conclude that this number should be at least 1000. The discrepancy might be caused by the false-negative result of the PCR test or the occurrence of infection after the test.

Infection Density and Epidemic Size of COVID-19 in China outside the Hubei province

The novel coronavirus (COVID-19) has spread to almost all countries in the world, claiming more than 160,000 lives and sickening more than 2,400,000 people by April 21, 2020. There has been research showing that on average, each infected person spreads the infection to more than two persons. Therefore the majority of the population is at risk of infection if no intervention measures were undertaken. The true size of the COVID-19 epidemic remains unknown, as a significant proportion of infected individuals only exhibit mild symptoms or are even asymptomatic. A timely assessment of the evolving epidemic size is crucial for resource allocation and triage decisions. In this article, we modify the back-calculation algorithm to obtain a lower bound estimate of the number of COVID-19 infected persons in China outside the Hubei province. We estimate the infection density among infected and show that the drastic control measures enforced throughout China following the lockdown of Wuhan City effectively slowed down the spread of the disease in two weeks. Our findings from China are expected to provide guidelines and enlightenment for surveillance and control activities of COVID-19 in other countries around the world.

Relationship between the ABO Blood Group and the COVID-19 Susceptibility

The novel coronavirus disease-2019 (COVID-19) has been spreading around the world rapidly and declared as a pandemic by WHO. Here, we compared the ABO blood group distribution in 2,173 patients with COVID-19 confirmed by SARS-CoV-2 test from three hospitals in Wuhan and Shenzhen, China with that in normal people from the corresponding regions. The results showed that blood group A was associated with a higher risk for acquiring COVID-19 compared with non-A blood groups, whereas blood group O was associated with a lower risk for the infection compared with non-O blood groups. This is the first observation of an association between the ABO blood type and COVID-19. It should be emphasized, however, that this is an early study with limitations. It would be premature to use this study to guide clinical practice at this time, but it should encourage further investigation of the relationship between the ABO blood group and the COVID-19 susceptibility.

Three-dimensional anatomical analysis of the perpendicular plate of ethmoid among Chinese and its safety harvesting range in rhinoplasty / 中华整形外科杂志

Objective@#To investigate the morphology and structure of the perpendicular plate of ethmoid and measure its anatomical parameters among Chinese population. To discuss the safety range of harvesting perpendicular plate of ethmoid in rhinoplasty.@*Methods@#Sixty-four healthy Chinese were included in accordance with certain requirements and their paranasal sinus was examined using 64 slices computed tomography (CT). The three-dimensional (3D) structure of their perpendicular plate of ethmoid was reconstructed, and the area, length, height and thickness were measured by Mimics 17.0 software. Statistical analysis was completed by SPSS 22.0 software and was checked out by t-test.@*Results@#According to the result from 3D anatomical analysis, the length of the anterior border of perpendicular plate of ethmoid was (28.58±2.91) mm, the inferior border was (26.17±5.76) mm and the posterior border was (19.84±3.17) mm. The thickness of the anterior border three sections were (3.07±0.72) mm, (3.09±0.73) mm and (1.75±0.55) mm respectively. The thickness of the inferior border in three sections were (1.96±0.62) mm, (1.94±0.73) mm and (1.87±0.67) mm, respectively. The length of the middle and lower third of the perpendicular plate of ethmoid anterior border was (10.04±2.39) mm. As to the superior border, the length was (35.31±6.52) mm. The total area of the perpendicular plate of ethmoid was (1 057.85±184.38) mm2, the lower section area was (474.09±109.60) mm2, and the ratio of middle and lower third to the total area was 0.45±0.07.@*Conclusions@#The thickness of the lower 1/3 segment of the vertical plate of the ethmoid bone is thinner than that of the upper segment, and it is far away from the skull base, which is easily to harvest and meet the application in surgery.

Application of Nipple Retractor for Correction of Nipple Inversion: A 10-Year Experience.

BACKGROUND: Nipple inversion is a relatively common problem in adolescent and adult women; however, most present surgical treatments are prone to injure the lactiferous ducts and impair the breast feeding function. A nipple retractor was developed by us in 2003 to correct nipple inversion to avoid lactiferous duct injury. The details and a 10-year evaluation of this technique were introduced in this paper. METHODS: The nipple retractor was made from the hollow end of single-use syringe, then eight holes were punctured for sutures crossing the base, and the height of retractor depended on the sizes of nipple-areola complex and breast volume. Two sutures were made to cross beneath the base of the nipple to elevate the nipple, and the hollow retractor was placed on the areola with the nipple and four ends of the sutures in the center, sutures then passed the prefabricated holes on the retractor base and were fixed with knots and suitable tension. The retractor was worn for 3-6 months and then could be removed. RESULTS: A total of 257 nipples in 136 patients with nipple inversion (unilateral: 15 patients; bilateral: 121 patients) received this operation from Jan 2003 to Dec 2012, among which 233 nipples were successfully corrected (90.7 %), and 24 nipples reoccurred in 2 years. The effective rates of grade I and grade II inversions were significantly higher than that of grade III (P < 0.01). Thirty-two patients with 56 treated nipples underwent labor and breastfeeding, and all the nipples were functional. The complications included fistula after suture removal (19 nipples, 7.4 %), breaking of suture (8 nipples, 3.1 %), erosion of nipple (28 nipples, 10.9 %), and chronic pain (10 nipples, 3.4 %), and all these complications were properly managed. CONCLUSION: The nipple retractor technique is a feasible, effective, and safe method for correction of grade I and grade II nipple inversions, and could also be indicated for primary correction of grade III inversion. Its most significant advantage is that lactiferous duct injury can be avoided and the breast feeding function preserved. LEVEL OF EVIDENCE V: Nipple inversion is a common malformation in adolescent and adult women, which can be present unilaterally or bilaterally. It was generally initiated from the adolescent period and could be caused by primary hypogenesis of smooth muscle and supporting tissue of the nipple-areola complex or hypoplasia of lactiferous ducts [1] . Some other secondary factors such as chronic infection, tumor, and previous surgery could contribute to the fibrosis, and some of them were believed to be congenital and hereditary [2, 3]. Since the openings of lactiferous ducts are immersed, inversion might cause reoccurring infection and breast feeding difficulty, and the appearance of the breast would be affected as well, which would impact patients' psychological health. Nipple inversion can be clinically divided into three categories according to Han et al.'s grading rules. In grade I, the nipple is easily pulled out manually and maintains its projection quite well. In grade II, the nipples can be pulled out but cannot maintain projection and tend to go back again. In grade III, the nipple can hardly be pulled out manually. [4] The images of three grades of nipple inversion are present in Fig. 1. Fig. 1 Three categories of nipple inversion grade I inverted nipple(a), grade II inverted nipple(b), grade III inverted nipple(c) Surgical interventions are the most effective treatments at present; however, injury to lactiferous ducts is inevitable in most surgical techniques [1, 5-10]. Some conservative nonoperative techniques have been developed in the last several years, such as a self-retraction and suction device, but only mild cases of grade I are indicated. Several suspension and retraction devices have been reported in recent years [10, 11], and the effect was acceptable, but long-term results were not reported. To simplify the operation procedures and diminish the possibility of lactiferous duct injury, we developed a nipple retractor, which was made from a single-use syringe, to correct nipple inversion from 2003. The details of procedures and techniques are introduced in this paper, as well as a 10-year retrospective analysis.

Nursing and effect of cyclogest in threatened abortion treatment / 现代临床护理

Objective To explore the effect of cyclogest and femotroneinthreatened abortion treatment and summerize key points of nursing. Methods Forty-two cases of first trimester threatened abortion women were selected from department of gynecology and obstetrics, which were randomly divided into the control group (n=21) and experiment group (n=21)using random digit table. The control group was given femotrone 40mg intramuscular injection each day while the experiment group was given 90 mg of vaginal progesterone suppository (Cyclogest) each day. Compare the improvement of symptoms, the success rate of pregnancy, changes in serum human chorionic gonadotropin (HCG) and progesterone. Results The improvement of symptoms, curative effects and change of HCG of both groups were no significantly difference. But elevatorconcentration of serum progesterone in femotrone group was higher than that of the cyclogest groupwith statistically difference. Conclusions Although cyclogest cannot appear significantly in increasing serum progesterone levels, it has the same effect as femotrone. Recommendations and notes about the use and side effects of cyclogest and femotrone should be provided for education to alleviate concerns of patients.

Comparison of insulin resistance and pancreatic β cell function between the pregnant women with normal and abnormal glucose metabolism / 中华内分泌代谢杂志

Objective To observe and compare the variation of insulin resistance and pancreatic β-cell function in pregnant women with abnormal and normal glucose metabolism during the first,second,and third trimesters,and to explore the feasibility of early diagnosis of gestational diabetes mellitus(GDM).Methods This is a prospective study.507 pregnant women with regular antenatal care from February 2009 to March 2010 were included in the study.Based on the results of oral glucose tolerance test,the patients with GDM consisted of 58,86,and 66 subjects respectively in the first,second,and third trimesters.The control group included 72,164,and 66 subjects respectively in the first,second,and third trimesters.Homeostasis model assessment insulin resistance index( HOMA-IR),homeostasis model assessment β-cell function (HOMA-β),area under curve of glucose (AUCG),area under curve of insulin ( AUCI ),30-minute insulin increase to 30-minute glucose increase ( △I30/△G30 ),and insulin sensitivity index composite(ISIcomp) were calculated for the evaluation of insulin resistance and pancreatic β-cell function.Results ( 1 ) AUCG and AUCI in the GDM group were statistically higher than those in control group while △I30/△G30and ISlcomp in the GDM group were statistically lower than those in the control group during the first trimester(P＜0.05),but HOMA-IR showed no statistically significant difference between two groups.In the GDM groups HOMA-IR,AUCG,and AUCI were statistically higher,whereas △I30/△G30 and ISIcomp were statistically lower than those in the control groups during the second and third trimesters (P ＜ 0.05 ). HOMA-β showed no statistically significant differences between the GDM groups and control groups during 3 trimesters.( 2 ) During thefirst,second,and third trimesters,blood glucose reached its peak by 0.5 h in the oral glucose tolerance test,and insulin reached its peak by 0.5-1 h in the control groups; while in the GDM groups the respective figures were 1 h and 2 h.Conclusions The insulin resistance in GDM patients diagnosed during the first,second,and third trimesters was higher than in pregnant women with normal glucose metabolism,and the peaks of blood glucose and insulin reached in oral glucose tolerance test were respectively delayed.The impaired pancreatic β-cell insulin secretion in GDM patients was present from early pregnancy.Thus for high-risk groups,oral glucose tolerance test during early pregnancy will be helpful for screening abnormal glucose metabolism.

PHARMACOKINETIC STUDY OF CEFUROXIME / 中国药理学通报

Clinical pharmacological study of cefuroxime was carried out in 8 normal volunteers. The drug obeyed two-compartment model kinetics in serum. The mean peak serum concentrations were 32.14, 89.06 and 63.11 (.is/ml respectively after IM, IV injection and IV infusion of 0.75g cefuroxime. Serum concentrations after IV administration dec re- ased rapidly, the elimination half lives ranged from 1.05-1.48 hours Absorption after IM injection was rapid and complete, the bioava-ilability being 98.89%,The apparent volume of distribution. ranged from 0.34 L/kg to 0.37 L/kg after IM and IV administration which showed that cefuroxime distributed mainly in extracellular fluid.The mean urinary recovery of cefuroxime was more than 90% within 24 hours after the administration of the drug.Based on its pha.rmacokinetic characteristics and antimicrobial activity, a therapeutic regimen is suggested for use in the treatment of various infections.