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Objective:Clinical and genetic analysis were conducted in 2 patients with hypophosphatasia(HPP) and their families to explore the pathogenic mechanism of HPP.Methods:The genomic DNA was extracted from peripheral blood of two patients with HPP and their family members. Sanger sequencing and pedigree verification were performed on the pathogenic variants identified using whole-exome sequencing. Then the function of the mutation sites was analyzed with bioinformatics software.Results:Proband 1 presented with developmental retardation, pectus funnel and premature loss of deciduous tooth, of which the serum alkaline phosphatase level was slightly lower than the bound of the normal range. Two complex heterozygous missense variants c. 1120G>A and c. 1334C>G of ALPL gene were detected in the proband 1 which were inherited from his parents respectively, showing an autosomal recessive inheritance. Both the variants were predicted to inflict deleterious effects on ALPL gene function by multiple bioinformatics program, and were classified as likely pathogenetic variants according to American College of Medical Genetics and Genomics(ACMG) guidelines. Proband 2 showed three missing permanent teeth and the significantly lower level of serum alkaline phosphatase than normal range. A heterozygous variant c. 1190-3C>G of ALPL gene was detected in proband 2 whose pattern of inheritance was unknown. The clinical significance of this variant was unknown according to ACMG standards and guidelines. All of these variants were considered as novel since none of them has been reported. Along with the above combined results, proband 1 and 2 were diagnosed as childhood HPP and Odontohypophosphatasia, respectively.Conclusion:This study reinforced the relationship between HPP and variants in ALPL gene. Two variants, c. 1120G>A and c. 1334C>G, were located in the homodimer interface and crown domain of tissue-nonspecific alkaline phosphatase(TNSALP), respectively, while c. 1190-3C>G were located in the splice sites, which might result in low TNSALP activity.
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Objective:To discuss the effective of artesunate in the treatment of coronavirus disease 2019 (COVID-19).Methods:Using prospective method, the 43 cases of confirmed COVID-19 patients in Nanning Fourth People's Hospital from January 22nd to February 15th in 2020 were enrolled and divided into routine treatment group ( n = 25) and artesunate treatment group ( n = 18) by odd-even rule after admission. According to the guidelines, the routine treatment group was recommended to receive lopinavir/ritonavir 500 mg + α-aerosolized interferon 500×10 4 U, twice daily; the artesunate treatment group was given artesunate 60 mg, twice daily besides the routine treatment, for 10 days in both groups. During the treatment period, the pharynx swab test of 2019 novel coronavirus (2019-nCoV) nucleic acid was carried out every 2 days, and the routine blood test, liver and kidney functions, blood coagulation function and myocardial enzymes were re-examined. Chest CT was checked every 3 days after the treatment, and re-examined every 5 days after the condition was improved. The routine blood test and biochemical results of two groups were observed, and the efficacy evaluation was performed by monitoring the time for significant improvement of symptoms, negative conversion time of throat swab virus nucleic acid, lung lesion absorption time, adverse drug reactions and the length of hospital stay of the two groups. Results:There were no significant differences between the two groups in terms of gender, age, body weight, routine blood test and biochemical results before treatment. In artesunate treatment group, the time for significant improvement of symptoms (days: 3.33±1.91 vs. 4.84±2.19), negative conversion time of 2019-nCoV nucleic acid (days: 4.72±2.16 vs. 6.68±3.76), lung lesion absorption starting time (days: 5.39±2.36 vs. 7.48±3.78), lung lesion absorption greater than 70% time (days: 14.11±4.16 vs. 17.04±4.42) and the length of hospital stay (days: 16.56±3.71 vs. 18.04±3.97) were significantly shorter than those in routine treatment group, with significant differences (all P < 0.05). The incidence of adverse drug reactions in two groups had no significant difference (72.2% vs. 80.0%, P > 0.05). Conclusion:Artesunate can shorten the treatment time of COVID-19, improve prognosis and eliminate pathogens, with fewer adverse reactions and a good application prospect.
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ObjectiveTo investigate the current situation of intensive care unit (ICU) inpatients in Infectious Disease Hospital of Nanning to provide a reference for the prevention and control of infectious diseases and construction and development of ICU in such a hospital.Methods The clinical data of inpatients from January 2011 to December 2015 in the Infectious Disease Hospital Affiliated to Guangxi Medical University (that is the Fourth People's Hospital of Nanning City) were retrospectively analyzed, and the distributions of patients with various diseases, ages, of the characteristics of children severe infectious diseases in ICU, the numbers of patients with infectious diseases in general ward and ICU, the average time and daily cost of hospitalization and mortality were conducted.Results During 2011 to 2015, 855 cases in ICU were treated, including 709 cases of infectious diseases, 146 cases of non-infectious disease. The top 5 infectious diseases were ranked as follows: tuberculosis, human acquired immune deficiency syndrome (AIDS), hand-foot-mouth disease (HFMD), viral hepatitis, tetanus, accounting for 96.47% of the total infectious disease inpatients in ICU; there were 25 cases of other legal infectious diseases, accounting for 3.53%, including dengue fever, measles, malaria, chicken pox, mumps, rabies, typhoid fever, paratyphoid fever, scrub typhus, bacillary dysentery, leptospirosis, human infections with highly pathogenic H7N9 avian influenza, epidemic hemorrhagic fever, A H1N1 influenza, and besides, critically ill patients carrying virus (viral hepatitis B and AIDS) in 7 pregnant women, 22 surgical patients, and 117 patients with internal medicine diseases were also admitted and treated. The top 4 infectious diseases causing deaths in ICU were tuberculosis, AIDS, viral hepatitis and HFMD: The infectious diseases with top 6 high mortalities in ICU were as follows: rabies, viral hepatitis, AIDS, tuberculosis and tetanus. The age range was wide in this study, from 73 days to 97 years, among which there were 167 cases of pediatric infectious diseases from pediatric department, accounting for 23.55% of ICU inpatients, being mainly severe HFMD, tuberculosis and severe varicella. From 2011 to 2015, the number of hospitalized patients showed a rising trend, and the average length of stay of patients in general wards presented a downward tendency, but the average time of hospitalization of inpatients with infectious disease in ICU, mortality and daily cost of hospitalization revealed a gradually increasing trend year by year.Conclusions It is of far-reaching significance to master the spectrum of dangerous severe infectious diseases to deal with the infectious disease epidemic situation and outburst with public health events.