Objective:To investigate the distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three urban and rural areas of Inner Mongolia.Methods:From March to October 2019, in 3 central cities (Chifeng, Hohhot, Ordos) and rural areas of Inner Mongolia, an epidemiological investigation method combining multi-stage stratified random sampling and face-to-face questionnaire survey was adopted to screen suspected AR patients, and skin prick test (SPT) was applied for diagnosis. At the same time, pollen monitoring was carried out in 3 areas to analyze the distribution and clinical sensitization characteristics of artemisia pollen.SPSS26.0 statistical software was used to process all the data. Chi-square test was used to compare rates among different age, sex, region and nationality, Spearman test was used to describe correlation analysis, and pairwise comparison of positive rates among multiple samples was used Bonferroni method.Results:Among the 6 393 subjects, 1 093 cases were diagnosed with AR, and the prevalence of AR was 17.10% (1 093/6 393). Among them, pollen-induced allergic rhinitis, the prevalence of PiAR was 10.97% (701/6 393), accounting for 64.14%(701/1 093).The highest incidence was in the youth group (20-39 years old), accounting for 46.94% (329/701).The diagnosed prevalence was higher in females than in males (11.35% vs. 10.64%, χ2 value 12.304, P<0.001).The prevalence rate of ethnic minority was higher than that of Han nationality (13.01% vs. 10.65%, χ2 value 6.296, P=0.008).The prevalence in urban areas was also significantly higher than that in rural areas (18.40% vs. 5.50%, χ2 value 10.497, P<0.001).There was significant difference in prevalence rate among the three regions in Inner Mongolia (6.06% in Chifeng, 13.46% in Hohhot, 16.39% in Ordos, χ2 value 70.054, P<0.001).The main clinical symptoms of artemisia PiAR were sneezing (95.58%), nasal congestion (91.73%) and nasal itching (89.30%).Allergic conjunctivitis accounted for 79.60% (558/701), chronic sinusitis for 55.63% (390/701), asthma for 23.25% (163/701).The pattern of artemisia pollen sensitization was mainly multiple sensitization, and the frequency of clinical symptoms and clinical diseases induced by hypersensitization with other allergens accounted for more than that caused by single artemisia pollen. The spread period of Artemisia pollen in the three regions was from June to October, and the peak state was in August in summer. The peak time of clinical symptoms in artemisia PiAR patients was about 2 weeks earlier than the peak time of pollen concentration, and the two were significantly positively correlated ( R=0.7671, P<0.001). Conclusion:Artemisia pollens are the dominant pollens in late summer and early autumn in Inner Mongolia, and the prevalence of artemisia PiAR is high. Controlling the spread of Artemisia pollens is of great significance for the prevention and treatment of AR.

Objective:To investigate the distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three urban and rural areas of Inner Mongolia.Methods:From March to October 2019, in 3 central cities (Chifeng, Hohhot, Ordos) and rural areas of Inner Mongolia, an epidemiological investigation method combining multi-stage stratified random sampling and face-to-face questionnaire survey was adopted to screen suspected AR patients, and skin prick test (SPT) was applied for diagnosis. At the same time, pollen monitoring was carried out in 3 areas to analyze the distribution and clinical sensitization characteristics of artemisia pollen.SPSS26.0 statistical software was used to process all the data. Chi-square test was used to compare rates among different age, sex, region and nationality, Spearman test was used to describe correlation analysis, and pairwise comparison of positive rates among multiple samples was used Bonferroni method.Results:Among the 6 393 subjects, 1 093 cases were diagnosed with AR, and the prevalence of AR was 17.10% (1 093/6 393). Among them, pollen-induced allergic rhinitis, the prevalence of PiAR was 10.97% (701/6 393), accounting for 64.14%(701/1 093).The highest incidence was in the youth group (20-39 years old), accounting for 46.94% (329/701).The diagnosed prevalence was higher in females than in males (11.35% vs. 10.64%, χ2 value 12.304, P<0.001).The prevalence rate of ethnic minority was higher than that of Han nationality (13.01% vs. 10.65%, χ2 value 6.296, P=0.008).The prevalence in urban areas was also significantly higher than that in rural areas (18.40% vs. 5.50%, χ2 value 10.497, P<0.001).There was significant difference in prevalence rate among the three regions in Inner Mongolia (6.06% in Chifeng, 13.46% in Hohhot, 16.39% in Ordos, χ2 value 70.054, P<0.001).The main clinical symptoms of artemisia PiAR were sneezing (95.58%), nasal congestion (91.73%) and nasal itching (89.30%).Allergic conjunctivitis accounted for 79.60% (558/701), chronic sinusitis for 55.63% (390/701), asthma for 23.25% (163/701).The pattern of artemisia pollen sensitization was mainly multiple sensitization, and the frequency of clinical symptoms and clinical diseases induced by hypersensitization with other allergens accounted for more than that caused by single artemisia pollen. The spread period of Artemisia pollen in the three regions was from June to October, and the peak state was in August in summer. The peak time of clinical symptoms in artemisia PiAR patients was about 2 weeks earlier than the peak time of pollen concentration, and the two were significantly positively correlated ( R=0.7671, P<0.001). Conclusion:Artemisia pollens are the dominant pollens in late summer and early autumn in Inner Mongolia, and the prevalence of artemisia PiAR is high. Controlling the spread of Artemisia pollens is of great significance for the prevention and treatment of AR.

Objective:To investigate the clinical features, diagnosis, treatment, and future sex selection in patients with partial androgen insensitivity syndrome (PAIS).Methods:Retrospective analysis of clinical data of three patients with PAIS who received treatment in The Third Affiliated Hospital of Xi'an Medical University, Beijing Ditan Hospital of Capital Medical University, and Beijing Yayuncun Amcare Women's and Children's Hospital from 2013 to 2015 was conducted. Physical signs, specialized examinations, surgical explorations, and treatments were analyzed. The Chinese database was searched, and 12 cases of PAIS were collected and summarized.Results:Fifteen patients with PAIS presented with primary amenorrhea (15/15). Special clinical manifestations included gender as male or appearing as male (5/15), penile dysplasia or clitoral hypertrophy (14/15), urethral dysplasia (5/15), and breast development (4/15). Eleven cases were treated based on female gender (including surgery and hormone replacement therapy). There were three special patients with PAIS who had specific etiology, genetics, clinical manifestations, histopathology, diagnosis, and treatment and ultimately underwent treatment based on female gender.Conclusion:PAIS is a rare form of disorder of sex development, featuring a karyotype of 46, XY, and is a congenital X-linked recessive condition. Understanding the pathogenesis of PAIS more thoroughly can contribute to accurate diagnosis, personalized treatment, and well-organized follow-up, thereby preventing gender dysphoria.

Streptococcus pyogenes Cas9 (SpCas9) has become a powerful genome editing tool, but has a limited range of recognizable protospacer adjacent motifs (PAMs) and shows off-target effects. To address these issues, we present a rational approach to optimize the xCas9 mutant derived from SpCas9 by directed evolution. Firstly, energy minimization with the Rosetta program was applied to optimize the three-dimensional structure of Cas9 to obtain the lowest energy conformation. Subsequently, combinatorial mutations were designed based on the mutations sites of xCas9 acquired during the directed evolution. Finally, optimal mutants were selected from the designed mutants by free energy ranking and subjected to experimental verification. A new mutant yCas9 (262A/324R/409N/480K/543D/694L/1219T) with multiple PAM recognition ability and low off-target effects was obtained and verified by DNA cleavage experiments. This mutant recognizes the NG, GAA and GAT PAMs and shows low off-target DNA cleavage activity guided by mismatched sgRNA, thus provides a gene editing tool with potential applications in biomedical field. Furthermore, we performed molecular dynamics simulations on the structures of SpCas9, xCas9 and yCas9 to reveal the mechanisms of their PAM recognition and off-target effects. These may provide theoretical guidance for further optimization and modification of CRISPR/Cas9 proteins.
CRISPR-Associated Protein 9/metabolism* ; CRISPR-Cas Systems/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats ; Gene Editing ; RNA, Guide/genetics* ; Streptococcus pyogenes/metabolism*

Objective:To investigate changes in the expression of Cosmc and T-synthase in peripheral B lymphocytes and in serum levels of galactose-deficient IgA1 (Gd-IgA1) in patients with Henoch-Sch?nlein purpura (HSP) .Methods:From January to August 2014, 56 patients with HSP were collected from outpatient or inpatient department of dermatology and venereology in the Second Hospital of Hebei Medical University, and were divided into 4 groups, including skin type group (22 cases) , joint type group (9 cases) , abdominal type group (12 cases) and renal type group (13 cases) . Twenty healthy volunteers served as healthy controls. Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of Cosmc and T-synthase in peripheral B lymphocytes, and a lectin-based enzyme-linked immunosorbent assay (ELISA) to detect the serum level of Gd-IgA1. Comparisons among multiple groups were performed using one-way analysis of variance or Kruskal-Wallis H test, multiple comparisons were performed using least significant difference (LSD) - t test or Nemenyi test, and correlation analysis was performed using Spearman rank correlation analysis. Results:There was a significant difference in the duration from disease onset to the clinic visit ( χ2= 26.19, P < 0.05) among the skin type group (6.27 ± 3.09 d) , joint type group (5.56 ± 3.05 d) , abdominal type group (6.75 ± 3.75 d) , and renal type group (26.23 ± 14.12 d) , and the duration from disease onset to the clinic visit was significantly longer in the renal type group than in the other 3 groups (all P < 0.05) . The Cosmc mRNA expression significantly differed among the skin type group, joint type group, abdominal type group, renal type group and healthy control group (0.849 ± 0.239, 0.767 ± 0.181, 0.719 ± 0.183, 0.459 ± 0.121, 1.146 ± 0.232, F= 23.37, P < 0.05) , was significantly lower in the 4 patient groups than in the healthy control group ( P < 0.01) , and lower in the renal type group than in the other 3 patient groups (all P < 0.01) . There was no significant difference in the T-synthase mRNA expression in peripheral B lymphocytes among the patient groups and healthy control group ( F= 1.05, P > 0.05) . The serum level of Gd-IgA1 significantly differed among the skin type group, joint type group, abdominal type group, renal type group and healthy control group ( F= 7.06, P < 0.05) . Moreover, the Gd-IgA1 level was significantly higher in the patient groups than in the healthy control group (all P < 0.05) , and higher in the renal type group than in the other 3 patient groups (all P < 0.05) . The serum level of Gd-IgA1 in the HSP patients was significantly and negatively correlated with the mRNA expression of Cosmc ( rs=-0.50, P < 0.01) . Conclusion:Decreased mRNA expression of Cosmc and increased serum levels of Gd-IgA1 were observed in patients with HSP, and there was a negative correlation between the two indices.

Objective:To investigate the demographic, epidemiological and clinical characteristics of measles in children, and to explore the risk factors for measles complicated with pneumonia in children.Methods:Children with measles aged≤18 years who were hospitalized in Jinan Infectious Disease Hospital from January 1, 2014 to December 31, 2018 were included. The demographic, epidemiological, clinical and laboratory data of inpatients were collected. The features of patients with pneumonia were analyzed. The risk factors of pneumonia were analyzed by chi-square test and multivariate logistic regression.Results:A total of 1 730 patients were recruited, including 423 patients (24.5%) in 2014, 437 patients (25.3%) in 2015, 856 patients (49.5%) in 2016, 10 patients (0.6%) in 2017 and four patients (0.2%) in 2018. The male to female ratio was 2∶1. The age ranged from four days to 18 years, and 1 572 patients (90.9%) were under three years old. There were 1 381 patients (79.8%) living in rural areas and 83 patients (4.8%) born with low birth weight. Two hundred and twenty-nine patients (13.2%) had a history of respiratory diseases within half a year before measles onset, and 1 489 patients (86.1%) had not been vaccinated before. According to the presence of pneumonia, 1 730 children with measles were divided into pneumonia group ( n=1 295) and non-pneumonia group ( n=435). There were more patients with bucking in pneumonia group than those in non-pneumonia group (56.8%(735/1 295) vs. 40.9%(178/435), χ2=32.770, P<0.01). Zero point seven percent (12/1 730) of children were critically ill, and 0.5%(8/1 730) of children died, all of whom were in pneumonia group. The white blood cell count, the percentage of white blood cell count>10×10 9/L, neutrophilic granulocyte count, the percentage of neutrophilic granulocyte count>7×10 9/L, C reactive protein level, the percentage of C reactive protein level>8.2 mg/L, procalcitonin level, the percentage of procalcitonin>0.5 ng/L, the percentage of hemoglobin level<110 g/L, and the percentage of albumin<35 g/L in pneumonia group were all significantly higher than those in non-pneumonia group ( t=7.153, χ2=47.239, t=8.297, χ2=41.176, Z=-6.769, χ2=40.131, Z=-4.119, χ2=19.284, χ2=7.465, χ2=18.356, respectively, all P<0.01). Multivariate logistic regression analysis showed that male (odds ratio ( OR)=1.316), living in rural areas ( OR=1.521), age7×10 9/L ( OR=3.666), and C reactive protein level >8.2 mg/L ( OR=1.871), procalcitonin>0.5 ng/L ( OR=1.711) were independent risk factors for pneumonia in children with measles. Conclusions:Measles vaccination in children should be farther strengthened. Male, children living in rural areas, low birth weight, history of respiratory diseases before measles and without measles vaccination are prone to be complicated with pneumonia, and special medical attention should be given.

Objective To understand the changes of serum tumor necrosis factor-α (TNF-α) among adults with Kaschin-Beck disease (KBD) in Qinghai,and to provide scientific data for KBD prevention and control.Methods A case-control study was used,according to "Diagnosis of Kaschin-Beck disease",104 cases of KBD patients [aged (47.61 ± 12.72) years old;50 males,54 females] and 95 cases of internal healthy controls [aged (48.28 ±14.87) years old;35 males,60 females],which were from KBD areas in Xinghai and Guide counties of Hainan Tibetan Autonomous Prefecture,Qinghai Province,and 73 cases of external healthy controls [aged (51.88 ± 13.93)years old;35 males,38 females] from non-KBD region of Xunhua County were included in July 2017.Serum TNF-α was determined via the enzyme linked immunosorbent assay (ELISA) method.Results Totally 272 persons were studied and divided into three groups,there was no statistical significant difference of ages among the three groups (F =2.236,P ＞ 0.05),meanwhile,there was no statistical significant difference of genders among the three groups (x2 =3.135,P ＞ 0.05).The serum TNF-α levels of KBD patients,internal and external healthy controls were (25.14 ± 10.29),(21.84 ± 9.37),and (24.98 ± 8.98) ng/L,respectively,which were statistically significantly different among the three groups (F =3.486,P ＜ 0.05).The serum TNF-α levels in the KBD group and the external healthy control were higher than that in internal healthy control (P ＜ 0.05).There was no significant difference between the KBD group and the external healthy control (P ＞ 0.05).Conclusion There may exist inflammatory changes among KBD patients in KBD areas of Qinghai Province.

Objective:To investigate the influence of endoplasmic reticulum stress (ERS) in the degeneration of cochlear hair cells in the type 2diabetic mice, and to clarify its mechanism.Methods:Twenty clean Kun Ming male mice aged one month were selected and randomly divided into control group and model group (n=10) .The mice in model group were injected with STZ (40 mg·kg-1) to establish the type 2diabetic models.The fasting blood glucose levels of the mice were measured through collecting the vena caudalis blood of the mice.Auditory brain stem response (ABR) was used to detect the ABR threshold of the mice.Otoacoustic emission (OAE) test was used to detect the OAE threshold of mice.The defect rate of mouse cochlear outer hair cells was calculated by the mouse cochlear spreading technique.The expression levels of GRP78, caspase-12, p-ERK and Nrf2proteins were detected by Western blotting method.Results:Compared with control group, the fasting blood glucose levels of the mice in model group at the 7th and the 14th days had no significant differences (P＞0.05) , but the levels were increased significantly at the 21th, 28th and 35th days and the level reached the highest value at the 35th day.The ABR thresholds of the mice in model group at 8, 12, and 24kHZ were increased significantly compared with control group (P＜0.05) .Under the stimulation of low frequency, there was no significant change in the OAE threshold of the mice in model grouop compared with control group.The OAE thresholds of the mice in model group were increased significantly under the medium frequency and high frequency stimulation compared with control group (P＜0.05) .The defects of the cochlear hair cells were mainly concentrated on the bottom of gyrus of the mice, and the defects in middle temporal gyrus and parietal gyrus were less.Compared with control group, the defect rate in the bottom of gyrus of the mice in model group was increased significantly (P＜0.05) ;the defect rates in the middle temporal gyrus and parietal gyrus were increased, but there was no significant difference (P＞0.05) .The expression levels of p-ERK and Nrf2in the cochlear hair cells of the mice in model group were lower than those in control group (P＜0.05) , and the expression levels of GRP78and caspase-12were higher than those in control group (P＜0.05) .Conclusion:ERS can result in the increase of defect rate of cochlear outer hair cells and ABR brainstem hearing threshold of the diabetic mice and decrease the expression levels of p-ERK and Nrf2proteins, suggesting that ERS can promote the degenerative lesions of cochlear hair cells in the type 2diabetic mice.

Objective: To explore the characteristics of adverse drug reactions (ADRs) in a grade three class A hospital to provide reference for rational drug use and reduction of ADRs. Methods: The new and serious ADRs reported during 2014 and 2016 were sta-tistically analyzed in terms of the report type, age, gender, administration route, drug variety and involving system. Results: The new and serious ADR reports reached to 400 cases, which accounted for 64. 52% of the total reports. Of the 400 ADR reports,there were 34. 25% distributed in the 60-74-year old. The proportion of male and female in the ADRs was basically equal, while that of male (50. 25% ) was slightly higher than that of female (49. 75% ). There were 57. 00% of ADRs caused by intravenous administration, and 31. 25% caused by anti-infective drugs, in which cephalosporins accounted for the most (32. 00% ). The most common manifesta-tion of ADR was damage to skin and its appendages, which accounted for 33. 00% , followed by the damage to gastrointestinal system (15. 50% ) and hepatorenal function (14. 00% ). Conclusion: Great attention should be paid to monitoring and reporting ADRs in our hospital, and drugs should be rationally used so as to reduce the occurrence of ADRs.

Objective To investigate the relationship between body composition and adequacy of dialysis,and analyze the related risk factors for inadequate delivery of hemodialysis.Methods In a prospective clinical trial,two different methods determining dialysis dose were simultaneously applied:Kt/Vdau (conventional method with Daugirdas' formula) and Kt/Vbem [online clearance monitoring (OCM) measurement with Ⅴ measured by body composition monitor (BCM)].Using the value of 1.27 as the boundary,the patients were divided into two groups:Kt/Vbcm ＜ 1.27 group and Kt/Vbcm≥ 1.27 group.Clinical indices were compared between the two groups.Multiple linear regression was applied to analyze the potential impact factors of the difference between Kt/V values calculated by the two methods.Receiver operator characteristic (ROC) curve was applied to analyze meaningful factors.Results A total of 138 maintenance hemodialysis patients with age of (54.9±12.7) years old were enrolled,and 55.1％ of them were males.There was no significant difference between Kt/Vdau and Kt/Vbcm [1.432(1.235,1.718) vs 1.434 (1.244,1.642),P=0.823].Kt/Vdau was incidentally prone to falsely high values due to operative errors,whereas in these cases OCM-based measurement Kt/Vbcm delivered realistic values.An excellent correlation was observed between Kt/Vdau and Kt/Vbcm;the mean difference was 0.07,95％CI (-0.66-0.79);the correlation coefficient was 0.842(0.821-0.862).The patients in Kt/Vbcm≥ 1.27 group had older age,lower body mass index (BMI),lower height and weight,lower total body water (TBW),lower extracellular water,lower intracellular water,and lower lean tissue index (LTI) compared to those in Kt/Vbcm ＜ 1.27 group.Excellent correlations were observed between Kt/Vbcm and TBW or LTI (r=-0.834,P ＜ 0.001;r=-0.721,P ＜ 0.001).ROC curve analysis showed that the sensitivity and specificity of predicting inadequate delivery of hemodialysis were 87.1％ and 86.5％,with a threshold of 30 L for TBW.It also showed that the sensitivity and specificity of predicting inadequate delivery of hemodialysis were 60.4％ and 94.6％,with a threshold of 11.05 kg/m2 for LTI.Conclusions BCM can give more accurate parameters of urea distribution volume,thus modifying the result of Kt/V.TBW and LTI are important risk influencing factors for inadequately dialysis,and special attention should be paid to patients with TBW ＞ 30 L or LTI ＞ 11.05 kg/m2.