Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective: To investigate the influencing factors of depressive symptoms among rural elderly patients with chronic diseases in China, so as to provide insights into depression prevention and control among the rural elderly patients with chronic diseases. Methods: The basic demographics, health status, and lifestyle of rural residents at ages of 65 years and older who had at least one chronic disease were retrieved from The Chinese Longitudinal Healthy Longevity Survey (CLHLS) database in 2018, and participants' depressive symptoms were assessed with The Center for Epidemiological Studies Depression-10 (CES-D-10) scale. Factors affecting the depressive symptoms were identified with a multivariable logistic regression model. Results: Totally 5 146 rural elderly patients with chronic diseases were enrolled, including 2 373 men (46.11%) and 2 773 women (53.89%). The prevalence of depressive symptoms was 27.13%. Multivariable logistic regression analysis identified having two and more children (OR=0.614, 95%CI: 0.387-0.975), living alone (OR=1.450, 95%CI: 1.192-1.764), life satisfaction (general, OR=1.933, 95%CI: 1.651-2.264; low, OR=5.366, 95%CI: 3.488-8.254), self-assessed health status (general, OR=2.697, 95%CI: 2.284-3.185; poor, OR=5.338, 95%CI: 4.262-6.685), disability in instrumental activities of daily living (OR=1.592, 95%CI: 1.328-1.908), sleep duration (normal, OR=0.502, 95%CI: 0.429-0.586; too long, OR=0.494, 95%CI: 0.405-0.603), exercise (OR=0.721, 95%CI: 0.607-0.856), watching TV (OR=0.787, 95%CI: 0.664-0.933), and gardening activities (OR=0.781, 95%CI: 0.626-0.975) as factors affecting depressive symptoms among rural elderly patients with chronic diseases. Conclusions The prevalence of depressive symptoms was 27.13% among rural elderly patients with chronic diseases. Number of children, living style, life satisfaction, health status, sleep duration, exercise, watching TV, and gardening activities are associated with the development of depressive symptoms among rural elderly patients with chronic diseases.

Objective:To investigate the iodine nutritional status of pregnant women in Qingdao and the effect of prevention and treatment of iodine deficiency disorders (IDD), so as to provide a basis for residents to supplement iodine scientifically, and take targeted prevention measures and adjust intervention strategies.Methods:In accordance with the requirements of the "National Iodine Deficiency Disorders Surveillance Program (2016 edition)" and "Shandong Iodine Deficiency Disorders Surveillance Program", the cluster sampling method was adopted to select pregnant women from 10 districts (cities) in Qingdao from 2018 to 2020, to investigate their basic information and thyroid disease history. Meanwhile, household edible salt samples and random urine samples were collected to detect iodine content.Results:A total of 3 000 pregnant women were monitored from 2018 to 2020, the median age was 31 years, and the median gestational age was 18 weeks. There were significant differences in the distribution of age, gestational age, whether senile puerpera, and pregnancy in different years ( H/χ 2 = 29.35, 81.03, 65.62, 77.34, P < 0.001). The median salt iodine of edible salt ( n = 3 000) and iodized salt ( n = 2 700) in pregnant women's homes were 23.02 and 23.70 mg/kg, respectively. The qualified rate of iodized salt, the coverage rate of iodized salt and the consumption rate of qualified iodized salt were 89.59% (2 419/2 700), 90.00% (2 700/3 000) and 80.63% (2 419/3 000). The comparison of qualified rate of iodized salt, coverage rate of iodized salt and consumption rate of qualified iodized salt among different years was statistically significant (χ 2 = 48.09, 36.62, 61.08, P < 0.001), the coverage rate of iodized salt and the consumption rate of qualified iodized salt showed a downward trend year by year (χ 2trent = 35.54, 29.50, P < 0.001). A total of 3 000 urine samples were collected from pregnant women and the median urinary iodine of pregnant women was 147.85 μg/L. The urinary iodine level in the third trimester was lower than that in the first and second trimesters ( P < 0.001). The urinary iodine level in the non elderly group was higher than that in the elderly group ( Z = - 6.66, P < 0.001). The urinary iodine level in the group without thyroid disease was higher than that in the group with thyroid disease ( Z = - 1.99, P = 0.047). The urinary iodine level in iodized salt group was higher than that in non-iodized salt group ( Z = - 2.42, P = 0.015). Conclusions:The iodine nutrition of pregnant women in Qingdao is generally at an insufficient level, and the risk of iodine deficiency is high, which needs attention. In recent years, the coverage rate of iodized salt and the consumption rate of qualified iodized salt in Qingdao have shown a downward trend, and have failed to meet the requirements of national standards. In the future, we should strengthen the monitoring and health education of IDD in pregnant women.

Background The pathogenesis of beryllium-induced pulmonary fibrosis is unknown and there is no specific treatment for the disease as yet. MicroRNA (miRNA) may play a role in the process of beryllium-induced pulmonary fibrosis. Objective To construct a microRNA-21 (miR-21) interfering cell line, and to investigate the effect of miR-21 on beryllium sulfate (BeSO₄)-induced fibrosis in human lung adenocarcinoma alveolar basal epithelial cells (A549 cells) and its potential mechanism. Methods The miR-21 target genes were predicted by the online database miRBase and verified by experiments using dual luciferase reporter gene. After transfecting A549 with miR-21interference lentivirus, puromycin was used to select a stable cell line. An in vitro model of pulmonary fibrosis was established using BeSO₄ infecting A549 cells with a concentration of 10 μmol·L⁻¹ and an exposure time of 48 h. Then the treated cells were divided into control group, model group, miR-21 interference group, and miR-21 interference control group. Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the relative expression level of miR-21 gene. Western blotting was used to detect the relative expression levels of TGF-β1/Smads pathway related proteins [Smad2, Smad3, p-Smad2, p-Smad3, Smad7, and transforming growth factor-β1 (TGF-β1)], myofibrosis cell marker α-smooth muscle actin (α-SMA), andextracellular matrix collagen-I (COL-I) and collagen-Ⅲ (COL-Ⅲ). Results The miRBase predicted that miR-21 had a binding site with Smad7, and the results of the dual luciferase reporter gene experiment showed that the target gene of miR-21 was Smad7. The construction of miR-21 interfered with A549 cell line was successful. Compared with the control group, the relative expression of miR-21 gene in the model group increased by 97.57%; the relative expression of Smad7 protein in the model group decreased by 15.48%; the relative protein expression of Smad2, Smad3, p-Smad2, p-Smad3, TGF-β1, α-SMA, COL-I, and COL-Ⅲ increased by 13.55%, 35.72%, 18.35%, 35.75%, 25.52%, 31.58%, 24.61%, and 11.66% respectively (P<0.05). Compared with the interference control group, the miR-21 gene expression level in the interference group decreased by 28.96%; the relative expression of Smad7 protein increased by 19.07%; the relative protein expression of Smad2, Smad3, p-Smad2, p-Smad3, TGF-β1, α-SMA, COL-I, and COL-Ⅲ decreased by 8.01%, 19.95%, 14.56%, 19.37%, 11.95%, 10.96%, 18.81%, and 31.36% repectively (P<0.05). There was no statistically significant difference in the gene abd protein expression levels of each gene between the model group and the interference control group (P>0.05). Conclusion In an in vitro model of pulmonary fibrosis induced by beryllium compounds, miR-21 may promote fibrosis by targeting Smad7 to regulate the TGF-β1/Smad signaling pathway.

Objective:To investigate the iodine nutritional status of children in Qingdao City and the effects of prevention and treatment measures on iodine deficiency disorders (IDD), and to provide a scientific basis for guiding residents to scientifically supplement iodine, taking timely targeted prevention and control measures, and scientifically adjusting intervention strategies.Methods:According to "National Iodine Deficiency Disorders Surveillance Program (2016 edition)" and "Iodine Deficiency Disorders Surveillance Program of Shandong Province", from 2018 to 2020, using the cluster sampling method, children aged 8-10 years in Qingdao City were chosen to test their household salt iodine content and random urinary iodine content, and to examine their thyroid volume by B-ultrasonography, and the correlation between thyroid volume and physical development indexes was analyzed.Results:From 2018 to 2020, a total of 6 057 children were monitored, including 3 068 boys and 2 989 girls. The median of salt iodine and iodized salt iodine of children was 23.50 and 24.10 mg/kg. The qualified rate of iodized salt was 89.95% (4 832/5 372), the coverage rate of iodized salt was 88.69% (5 372/6 057), and the consumption rate of qualified iodized salt was 79.78% (4 832/6 057). There were significant differences in the qualified rate of iodized salt, the coverage rate of iodized salt and the consumption rate of qualified iodized salt between different years (χ 2 = 135.26, 314.71, 342.87, P < 0.001). A total of 6 057 urine samples were collected from children, and the median of urinary iodine was 193.92 μg/L, of which 16.2% (979/6 057) were < 100 μg/L, and 22.5% (1 361/6 057) were ≥300 μg/L. There were statistically significant differences in the medians of urinary iodine between different years, gender and whether eating iodized salt ( H/Z = 37.25,-3.89,-5.69, P < 0.001), the median of urinary iodine in boys was higher than that of girls, and the median of urinary iodine in eating iodized salt group was higher than that of eating non-iodized salt group. There was no significant difference in the median of urinary iodine between different age ( H = 4.33, P = 0.119). The rate of goiter in children was 3.45% (71/2 057), and the difference between different years was statistically significant (χ 2 = 42.68, P < 0.001). The incidence of goiter in 2020 [7.31% (45/616)] was significantly higher than that in 2018 and 2019 [2.81% (18/641), 1.00% (8/800), P < 0.001]. Thyroid volume of children was positively correlated with height and weight ( r = 0.20, 0.22, P < 0.001). Conclusions:The iodine nutritional level of children aged 8-10 years in Qingdao City is appropriate. However, the incidence of goiter in children in some years is relatively high. The qualified rate of iodized salt, the coverage rate of iodized salt and the consumption rate of qualified iodized salt are all lower than the national standard for elimination of IDD, which should be paid attention to.

Objective:To evaluate the effect of prevention and control measures to drinking-water-borne endemic fluorosis in Qingdao, and to provide scientific basis for formulating prevention and control strategies.Methods:From 2019 to 2021, a full coverage surveillance was carried out in 1 146 villages in 7 drinking-water-borne endemic fluorosis areas in Qingdao, including the operation status of the water improvement and fluoride reduction project, the water fluoride content in the villages, and the prevalence of dental fluorosis among children aged 8-12 years.Results:From 2019 to 2021, all the 1 146 affected villages in Qingdao had improved their water supply, and the rates of water fluoride exceeding the standard were 7.16% (82/1 146), 1.40% (16/1 146) and 3.84% (44/1 146), respectively, and the differences between years were statistically significant (χ 2 = 48.36, P < 0.001). The detection rates of dental fluorosis in children aged 8-12 years were 3.11% (803/25 856), 2.68% (629/23 460) and 3.00% (655/21 846), respectively, and the differences between years were statistically significant (χ 2 = 8.26, P = 0.016). The detection rate of dental fluorosis among children in villages with qualified water fluoride (2.85%, 1 986/69 565) was lower than that in villages with excessive water fluoride (6.32%, 101/1 597), with a statistically significant difference (χ 2 = 67.74, P < 0.001). Conclusions:From 2019 to 2021, the effect of prevention and control measures to drinking-water-borne endemic fluorosis in Qingdao is significant and the detection rate of dental fluorosis in children is low, the detection rate of dental fluorosis in villages with qualified water fluoride is significantly lower than that in villages with excessive water fluoride. In the future, we should continue to strengthen water fluoride monitoring and engineering maintenance to ensure that the water fluoride content continues to be qualified and effectively reduce the harm of fluorosis.

Objective:To assess the operation and usage conditions of all water improvement projects in Qingdao, master the water fluoride content and the prevalence of dental fluorosis in children in drinking-water-borne endemic fluorosis villages, evaluate the prevention and control effect of water improvement project.Methods:From April to October in 2020, all drinking-water-borne endemic fluorosis villages in 7 cities (districts) of Qingdao were selected to investigate the operation and usage conditions of water improvement project, water fluoride and prevalence of dental fluorosis of 8 to 12 years old children. The prevention and control effect of water improvement project on drinking-water-borne endemic fluorosis in Qingdao was evaluated according to the control contents and criteria of drinking-water-borne endemic fluorosis.Results:There were 1 146 drinking-water-borne endemic fluorosis villages, the water improved rate of villages was 100.00% (1 146/1 146), the rate of normal operation of water improvement project was 99.91% (1 145/1 146). There were 1 130 villages with qualified water fluoride and the qualified rate was 98.60% (1 130/1 146). A total of 23 473 children aged 8 - 12 years old were examined, and 631 children were detected with dental fluorosis. The detection rate of dental fluorosis was 2.69% (631/23 473), the dental fluorosis index was 0.048, and the prevalence was negative. The detection rate of dental fluorosis of children in villages with excessive water fluoride (7.03%, 40/569) was higher than that in villages with qualified water fluoride (2.58%, 591/22 904, χ 2 = 41.235, P < 0.01). Conclusion:The operation and usage conditions of water improvement projects in 7 drinking- water-borne endemic fluorosis cities (districts) in Qingdao are good, and the detection rate of dental fluorosis in children is low, which has reached the national control standard.

Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.

Background Studies have shown that stress during pregnancy can affect the growth and development of fetuses and offspring, and this effect has sex differences, but the results are controversial, and there are few studies on the emotional damage of offspring of different sexes caused by stress during pregnancy. Objective This experiment is designed to observe the effect of chronic stress during pregnancy on emotional damage of offspring of different sexes. Methods Thirty-two SD female rats were randomly divided into a model group and a control group (16 rats in each group), 24 male rats were divided into a model mating group (n=16) and a control mating group (n=8). Each rat of the model group was reared in a single cage and received chronic unpredictable mild stress (CUMS) for 28 d, including hot water swimming for 5 min, cold water swimming for 5 min, tail pinching for 2 min, crowding for 24 h, moist bedding for 24 h, cage shaking for 30 min, and space restriction for 2 h. One stressor was administered daily and the same stressor did not repeat within 7 d. Blood was collected from the endocanthal vein of the two groups of female rats 1 d before and 1, 7, 14, 21, and 28 d after stress, the plasma was separated by centrifugation, and ¹³¹I radioimmunoassay was used to measure plasma corticosterone concentration. On postnatal day 21 (PND21), 16 offspring rats (half male and half male) were randomly selected from each group, their plasma corticosterone concentration was measured on PND28 and PND42, and their emotional damage was measured on PND42. Results The plasma corticosterone levels of dams in the model group on the 14th, 21th, and 28th days of stress [(394.02±97.40), (444.12±90.43), and (463.71±107.75) μg·L⁻¹] were higher than those in the control group [(285.63±81.64), (341.78±48.39), and (320.42±84.76) μg·L⁻¹] (all P< 0.05). On PND28 and PND42, the plasma corticosterone levels in the female model offspring group [(543.30±90.21) and (530.76±83.10) μg·L⁻¹] were higher than those in the female control offspring group [(397.77±64.27) and (325.78±61.03) μg·L⁻¹] (both P<0.05). In the sugar water preference test, the total fluid consumption [(10.74±1.28) mL], sugar water consumption [(5.50±1.30) mL], and 1% sucrose preference percentage [(20.36±3.41) %] in the female model offspring group were lower than those in the female control offspring group [(13.74±2.06) mL, (8.56±2.04) mL, and (62.11±8.05) %] (all P<0.05). In the open field test, the horizontal score, vertical score, and cleaning times of the male model offspring group were lower than those of the male control offspring group (all P<0.05). In the tail suspension test, the immobility time of the female and male model offspring groups [(126.95±39.88) and (70.24±28.98) s] was longer than the control offspring groups of the same sex [(54.30±24.99) and (38.63±18.91) s] (both P<0.05), and the duration of immobility time in the female model offspring group was longer (t=3.253, P=0.006). In the forced swimming test, the immobility time of the female model offspring group [(7.97±6.66) s] was longer than that of the female control offspring group [(1.85±2.12) s] (t=2.478, P=0.037). On PND42, the plasma corticosterone level of female offspring was negatively correlated with total fluid consumption, sugar water consumption, and 1% sucrose preference percentage (r=−0.621, r=−0.728, r=−0.699; P<0.05), and positively correlated with immobility time in the tail suspension test and immobility time in the forced swimming test (r=0.571, r=0.712; P<0.05), However, there was no correlation between plasma corticosterone and emotional indicators on PND42 in male offspring (P>0.05). Conclusion Chronic stress during pregnancy causes emotional damage to the offspring, and female offspring show depression-like behaviors.

Objective:To investigate the effect of chronic stress of pregnant rats on the gut microbiota of female rats and offspring, and explore the role of intestinal microbiota in chronic stress during pregnancy.Methods:In November 2019, SPF-grade healthy adult SD rats were selected. 16 female rats were randomly divided into control group and model group, with 8 in each group; 12 male rats were randomly divided into model mating group (8) and control mating group (4) . A model of chronic unpredictable mild stress (CUMS) during pregnancy was established. Blood samples were collected from the iliac vein of the female rats 1 day before and 1, 7, and 14 days after the CUMS protocol, and measured for plasma corticosterone content by radioimmunoassay. After the stress was completed, fresh feces of the female rats were collected for testing. The offspring's fresh stool samples were collected on postnatal day 20 (PND20) , and they were divided into control offspring group and model offspring group samples. The sequence of 16S rRNAV3-V4 regions of microorganisms in the feces of offspring was determined by Illumina MiSeq technique; and the interaction between microbial community structure and diversity were analyzed.Results:The content of plasma corticosterone in the model group was higher than that in the control group on the 7th and 14th day of stress ( P<0.05) . Compared with the control group, the Sobs index, Chao index, ACE index and Shannon index of the model group were decreased ( P<0.05) . The number of unique species abundance (OTU) in the control group was 130, and 91 in the model group. The relative abundance of female Firmicutes in the control group (64.87%) was higher than that in the model group, and the relative abundance of Bacteroides (31.72%) was lower than that of the model group (46.35%) . The Sobs index, Chao index, ACE index, Simpson index and Shannon index of the control offspring group were higher than those of the model offspring group ( P<0.05) . The number of unique OTUs in the model offspring group was 75, and 93 in the control offspring group. The relative abundance of Firmicutes (60.24%) in the control offspring group was higher than that of the model offspring group (52.95%) . Conclusion:Chronic stress during pregnancy can not only lead to the disorder of intestinal flora in female rats, but also lead to the change of intrauterine environment, thus affecting the diversity of intestinal flora in offspring.