Objective To understand the impact of system reform of salt industry on iodine nutrition of people in Gansu Province, and to provide a scientific basis for policy adjustment of relevant departments. Methods The investigation period (2014-2021) was divided into two sub-periods: before system reform of salt industry (2014-2016) and after system reform of salt industry (2017-2021). Thirty counties were selected according to the method of ^“population proportional probability sampling (PPS)^” in 2014. According to the iodine deficiency disease monitoring program of Gansu Province, from 2016 to 2021, children aged 8-10 years and pregnant women were taken as research objects to collect urine samples for urine iodine detection. Children in 2014 and 2018 were selected to measure thyroid volume. Results A total of 90 989 children urine iodine samples were investigated, and the median urinary iodine (MUI) of children was 194.70µg/L; 7 663 and 83,326 children's urinary iodine samples were investigated in the two periods, the MUI was 180.73 µg/L and 196.00 µg/L, respectively, and the difference was statistically significant (P<0.05). A total of 44 741 pregnant women's urinary iodine samples were investigated, and the MUI of pregnant women was 176.50 µg/L; 4 480 and 40 261 pregnant women's urinary iodine samples were investigated in the two periods, the MUI was 160.61 µg/L and 178.10 µg/L, respectively, and the difference was statistically significant (P<0.05). The thyroid volume of 1 555 children and 8 509 children was investigated in the two periods, the median thyroid volume was 2.70 mL and 2.55 mL , respectively, and the difference was statistically significant (P<0.05). The rates of goiter in children were 3.15% and 1.26%, respectively, and the difference was statistically significant (P<0.05). Conclusion The iodine nutrition of people in Gansu Province has not fluctuated significantly after the reform of salt industry system and has maintained an appropriate level. It is necessary to pay attention to the potential risk of insufficient iodine nutrition level and thyroid health of key populations such as children and pregnant women and strengthen health education of scientific iodine supplementation.

Presbycusis is a disease characterized by hidden and slowly progressive bilateral sensorineural hear-ing loss.Its occurrence and development is a multifactorial process.The expression of each factor varies greatly a-mong individuals.Currently,there have been some studies on the pathogenesis of presbycusis,which can be catego-rized into ion channel abnormalities,cochlear synaptopathy,reactive oxygen species,hormone effects,mitochondrial abnormalities,genetic factors and vari other factors.This review summarizes the pathogenesis of presbycusis in re-cent years.

Objective:To explore the clinical characteristics of children with septic shock and analyze the drug resistance of blood culture positive bacteria.Methods:The clinical data,positive blood culture strains and drug sensitivity results of 127 children with septic shock admitted to the Department of Intensive Care Medicine of Hunan Children's Hospital from September 2015 to August 2021 were retrospectively analyzed.Results:A total of 134 strains of bacteria or fungi were isolated from the blood culture samples of 127 children with septic shock,and gram-negative strains were the main ones,accounting for 67.16% (90/134).Haemophilus influenzae and Escherichia coli were the main gram-negative bacteria,accounting for 38.81% (52/134) and 20.15% (27/134)，respectively,while Streptococcus pneumoniae was the main gram-positive bacteria,accounting for 8.21% (11/134),and Candida albicans was the main fungus,accounting for 10.45% (14/134).The number of white blood cells,the levels of serum C-reactive protein,procalcitonin,venous blood sugar and arterial blood lactic acid in patients were all significantly higher than normal values,and the white blood cells count and neutrophil percentage in gram-positive bacterial infections were significantly higher than those with gram-negative bacterial infections and fungal infections( P<0.05).Procalcitonin increased most obviously when infected by gram-negative bacteria,and the difference was statistically significant ( P<0.05).Gram-positive strains were sensitive to vancomycin,teicoplanin,and linezolid,but only 50% of Streptococcus pneumoniae were sensitive to penicillin.Gram-negative strains had relatively high drug resistance,among which Klebsiella pneumoniae were only highly resistant to imipenem,cilastatin and levofloxacin,reaching 50%.Haemophilus influenzae was resistant to cephalosporins and β-amides enzyme antibiotic,and the drug sensitivity rate of lactamase antibiotics was high,with a resistance rate of 50% only to ampicillin,cefuroxime,amikacin,and compound sulfamethoxazole.There were not many fungal strains,and most antifungal drugs were effective against blood culture-positive fungi. Conclusion:The main pathogens of infection in children with septic shock are gram-negative bacteria,and have high resistance to general antibiotics.We should pay attention to their drug resistance when using antibiotics empirically.

Objective:To investigate the intelligence status of children aged 10 - 12 in rural areas of Linxia Hui Autonomous Prefecture (referred to as Linxia) in Gansu Province.Methods:From September to November 2019, a cross-sectional study was carried out to investigate the intelligence status of children aged 10 to 12 in 8 counties (cities) of Linxia. Chinese Raven's Progressive Matrices (rural version) was used for intelligence test and children's intelligence quotient (IQ) was calculated by regular mold to evaluate children's intelligence level.Results:A total of 1 721 children in Linxia were tested for intelligence, with an average IQ of 103.2. Among them, low intelligence (≤69) accounted for 1.0% (18/1 721), borderline (70 - 79) accounted for 3.0% (52/1 721), middle and lower (80 - 89) accounted for 8.4% (144/1 721), moderate (90 - 109) accounted for 56.6% (974/1 721), middle and upper (110 - 119) accounted for 21.9% (377/1 721), excellent (120 - 129) accounted for 7.8% (135/1 721), extremely excellent (≥130) accounted for 1.2% (21/1 721). There were 635, 598 and 488 children aged 10, 11 and 12, respectively, with an average IQ of 106.1, 103.3 and 99.2. There were 919 males and 802 females, with an average IQ of 102.9 and 103.4, respectively.Conclusion:In 2019, the intelligence of children aged 10 to 12 in rural areas of Linxia has reached the moderate level.

Objective:To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease.Method:This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result:Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged ( M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) ( κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) ( κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn′t affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions:Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

Objective:To summarize the current research status, assessment tools, and influencing factors of fatigue in patients receiving maintenance hemodialysis (MHD) and provide a reference for the management of fatigue in this patient population.Methods:A literature search was conducted in databases including PubMed, Web of Science, ProQuest, Cochrane Library, Science Direct, Embase, CINAHL, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc for studies related to fatigue in patients receiving MHD. The search timeframe was from establishing the databases to January 23, 2024.Results:A total of 46 studies were included. Various assessment tools for fatigue in patients receiving MHD were identified, though specific tools were limited. The Short Form 36 Vitality Subscale (SF-36 VS) was the most commonly used assessment tool. The main factors influencing fatigue in these patients included sociodemographic, dialysis-related, disease-related, physical, nutritional, and psychological factors.Conclusions:Fatigue is a significant symptom in patients receiving MHD. Healthcare professionals must develop specific tools for accurately assessing fatigue in this population and explore standardized management plans.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the main pathogen that causes COVID-19,which is fast-mutating and highly transmissible.The infection has led to a global epidemic.As the main preventive and control measure,vaccination plays a critical role in fighting a-gainst COVID-19.Although a large number of epitope-based and mucosal vaccines have been stud-ied,few peptide epitope vaccines targeting the mucosa and their functional evaluation have been re-ported.In this study,we used SARS-CoV-2 structural protein M peptide epitope predicted by the IEDB database as an antigenic target to design the MS-3S gene containing 3 050 and 1 229 signal peptides and DCpep optimized for insertion into MS2 phage coat proteins.The expression plasmid pSIP:MS-3S was constructed by cloning the PCR fragments seamlessly and was transformed into Lactiplantibacillus plantarum 18 to obtain the recombinant bacterium LP18:MS-3S.Expression conditions such as induction time,inducer concentration,rotational speed and initial pH were opti-mized.The intranasal immunization experiments were performed to examine the vaccine efficacy.The results showed that the 916 bp-long target gene MS-3S modified and optimized was amplified and used to successfully construct the recombinant bacterial strain LP18:MS-3S.The optimal con-ditions for recombinant protein expression were obtained and verified by Western blot,flow cy-tometry,immunofluorescence and other detection methods.The optimal expression conditions were determined as follows:induction time was 4 h with 100 pg/L of SppIP as the optimal induction concentration.Antibody-specific for the epitope was verified by ELISA experiments in serum,alve-olar lavage fluid and fecal dilutions of mice.In summary,a recombinant bacterial strain expressing the epitope antigen of the SARS-CoV-2 M protein peptide was constructed.The obtained protein can induce the body to produce humoral and mucosal immunity,which lays the foundation for the development of a vaccine candidate for the mucosal immunity of COVID-19.

This paper discussed how to set the limit of impurities in the quality standard when the impurities in small-molecular innovative drugs were metabolites.Firstly,through the analysis and interpretation of each relevant guideline,in combination with the review cases of FDA and EMA,found out the conditions for qualification of im-purity,and then establ ish the acceptable limit of impurities based on the test results of multiple batches,the incre-ments of production process and storage process.

Objective:To analyze the monitoring data of Kashin-Beck disease (KBD) in Gansu Province and learn about the long-term trend of KBD incidence.Methods:The X-ray detection rate of children with KBD in Gansu Province from 1990 to 2021 was collected through Gansu Provincial Center for Disease Control and Prevention. Joinpoint regression model was used to analyze the trend of X-ray detection rate of KBD in children. The annual percent change (APC) and average annual percent change (AAPC) were used to analyze the trend of the observed indicators. In addition, a polynomial regression model was constructed to fit the change of X-ray detection rate of children with KBD over time.Results:From 1990 to 2021, a total of 126 726 children were examined for KBD by X-ray in Gansu Province, with 3 011 positive cases, X-ray detection rate of KBD in children was 0 in 2019 - 2021. Joinpoint regression model analysis showed that the X-ray detection rate of children with KBD in Gansu Province from 1990 to 2018 showed a decreasing trend (AAPC = - 14.40%, P = 0.001). The APC of 1990 - 1998, 2002 - 2008 and 2008 - 2012 was - 17.75%, - 21.89% and - 49.89%, respectively, showing a decreasing trend ( P < 0.05). The APC of 2012 - 2018 was 6.15%, but the trend change was not statistically significant ( P = 0.475). The curve fitting of X-ray detection rate of KBD in children in Gansu Province over time was carried out, and the quadric polynomial equation was y = 0.000 314 5 x4 - 0.021 37 x3 + 0.487 1 x2 - 4.635 x + 22.08. Conclusions:The condition of KBD in children of Gansu Province has been effectively controlled. The X-ray detection rate has remained at a relatively low level since 2012, and it has reached a state of elimination since 2019.

Phage therapy is one of the most important tools for the treatment of infections with multi-drug resistant bacteria. Such phages are usually isolated from hospital effluents, however, no systematic study on the distribution of phages in hospital effluents has been conducted so far. The aim of this study was to isolate the corresponding phages of common pathogenic bacteria isolated in the clinic as hosts, so as to assess the ecological distribution of phages in hospital wastewater and to provide a reference for the isolation and application of phages of drug-resistant bacteria in the clinic. A cross-sectional study design was used in this study. The 125 pathogenic bacteria (belonging to 16 different strains) isolated from the clinical microbiology laboratory of Qilu Hospital of Shandong University from May to June 2023 were selected as the target strains, and the phages corresponding to these strains were isolated and purified from the hospital wastewater by using the double-layer plate sandwich method. At the same time, the distribution of pathogenic bacteria in the same batch of wastewater was analyzed with the help of mNGS sequencing technology, so as to preliminarily investigate the abundance correspondence between pathogenic bacteria and phages in wastewater. The results showed that a total of 56 phage strains were isolated from 125 clinical pathogens as hosts, corresponding to six pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. All six pathogenic bacteria contained strains with different degrees of drug resistance, with a higher percentage of multi-drug resistant strains in A. baumannii, Escherichia coli and P. aeruginosa. The phage acquisition rates of these six pathogens were, in descending order, Escherichia coli (80%), Stenotrophomonas maltophilia (75%), Pseudomonas aeruginosa (70%), Klebsiella pneumoniae (66.67%), Acinetobacter baumannii (36.36%) and Staphylococcus aureus (12.5%). Preliminary mNGS sequencing results showed that the pathogenic bacteria with higher abundance in the batch of effluent were Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Acinetobacter baumannii, Klebsiella aerogenes, Klebsiella michiganensis and Pseudomonas aeruginosa. In conclusion, phages of most common clinical Gram-negative pathogens were isolated from hospital wastewater with high isolation rates; however, phages of Gram-positive pathogens were isolated at lower rates, and only phages corresponding to Staphylococcus aureus were isolated in this study. The corresponding mNGS sequencing results showed that the distribution of Gram-negative pathogens in sewage may had a positive correlation with the ecological distribution of phages.