The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery. In this study, by screening fungal extracts against coxsackievirus B3 (CVB3), three new aspochalasins, templichalasins A‒C (1‒3), along with six known aspochalasins (4‒9) were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045. Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system, while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons. Their structures were characterized through extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Additionally, we demonstrated that compound 4 can be readily converted into compounds 1‒3 under mild acidic conditions and proposed a plausible mechanism for this conversion. Bioactivity evaluation of compounds 1‒9 against CVB3 revealed the inhibitory effects of all compounds against the virus. Notably, compound 9 exhibited superior antiviral activity, surpassing the commercial drug ribavirin in selectivity index (SI) value.
Antiviral Agents/isolation & purification* ; Aspergillus/chemistry* ; Molecular Structure ; Enterovirus B, Human/drug effects* ; Endophytes/chemistry* ; Cytochalasins/isolation & purification* ; Drug Discovery ; Humans

Objective:To investigate the current situation and changing trends of coal-burning-borne endemic fluorosis (coal-burning-borne fluorosis) areas in Henan Province, and evaluate the effectiveness of prevention and control measures.Methods:From 2019 to 2021, monitoring was carried out in all villages affected by coal-burning-borne fluorosis in Henan Province. A simple random sampling method was used to select 30 households in each affected village each year to investigate the use of stoves and the formation of related healthy living behaviors. According to the criteria of "Diagnosis of Dental Fluorosis" (WS/T 208-2011), all children aged 8 to 12 in the affected villages were examined for dental fluorosis. The evaluation for control and elimination of the disease areas was carried out in accordance with the "Evaluation Approach for Control and Elimination of Priority Endemic Diseases (2019 Edition)".Results:From 2019 to 2021, a total of 7 472 households were monitored, the rate of qualified improved stoves were all ≥99.80%, the correct use rate of qualified improved stoves and correct drying of corn and pepper were reached 100%. From 2019 to 2021, the prevalence of dental fluorosis in children was 5.38% (237/4 405), 5.18% (232/4 477), and 3.68% (145/3 937), respectively, showing a declining trend (χ 2trend = 12.73, P < 0.001). The prevalence of dental fluorosis among children in affected villages was less than 15%. From 2019 to 2021, all affected villages in coal-burning-borne fluorosis in Henan Province had met the elimination criteria. Conclusion:Coal-burning-borne fluorosis areas in Henan Province have been continuously eliminated, with significant prevention and control effects, and the disease has been effectively controlled.

Objective:To investigate the current situation and changing trends of coal-burning-borne endemic fluorosis (coal-burning-borne fluorosis) areas in Henan Province, and evaluate the effectiveness of prevention and control measures.Methods:From 2019 to 2021, monitoring was carried out in all villages affected by coal-burning-borne fluorosis in Henan Province. A simple random sampling method was used to select 30 households in each affected village each year to investigate the use of stoves and the formation of related healthy living behaviors. According to the criteria of "Diagnosis of Dental Fluorosis" (WS/T 208-2011), all children aged 8 to 12 in the affected villages were examined for dental fluorosis. The evaluation for control and elimination of the disease areas was carried out in accordance with the "Evaluation Approach for Control and Elimination of Priority Endemic Diseases (2019 Edition)".Results:From 2019 to 2021, a total of 7 472 households were monitored, the rate of qualified improved stoves were all ≥99.80%, the correct use rate of qualified improved stoves and correct drying of corn and pepper were reached 100%. From 2019 to 2021, the prevalence of dental fluorosis in children was 5.38% (237/4 405), 5.18% (232/4 477), and 3.68% (145/3 937), respectively, showing a declining trend (χ 2trend = 12.73, P < 0.001). The prevalence of dental fluorosis among children in affected villages was less than 15%. From 2019 to 2021, all affected villages in coal-burning-borne fluorosis in Henan Province had met the elimination criteria. Conclusion:Coal-burning-borne fluorosis areas in Henan Province have been continuously eliminated, with significant prevention and control effects, and the disease has been effectively controlled.

Objective:To compare iodine nutritional status of different populations consuming iodized salt and non-iodized salt in iodine adequate areas, and to provide a basis for formulating iodine supplementation strategies.Methods:In October 2021, Luyi County in Henan Province was selected as an iodine adequate area consuming iodized salt, while Ningling County was selected as an iodine adequate area consuming non-iodized salt. Stratified by water iodine (50 - 59, 60 - 69, 70 - 79, 80 - 89, 90 - 100 μg/L), one village was selected from each layer. One hundred children aged 8 - 10, one hundred adults, and 20 pregnant women were selected from each village to collect their urine and salt samples for testing salt and urinary iodine, and their thyroid gland was measured by ultrasound.Results:A total of 600 salt samples in Luyi County were collected, with the coverage rate of iodized salt (99.8%, 599/600) and the consuming rate of qualified iodized salt (95.5%, 573/600). A total of 1 008 salt samples in Ningling County were collected, with the rate of non-iodized salt (93.8%, 946/1 008). The median urinary iodine of children in Luyi County ( n = 240) was higher than that in Ningling County ( n = 468, 305.0 vs 232.0 μg/L, Z = - 8.10, P < 0.001). There was no statistically significant difference in median urinary iodine between pregnant women in Luyi County ( n = 120) and Ningling County ( n = 53, 240.0 vs 236.0 μg/L, Z = - 1.02, P = 0.306). The median urinary iodine of adults in Luyi County ( n = 238) was higher than that in Ningling County ( n = 486, 289.0 vs 178.5 μg/L, Z = - 11.14, P < 0.001). Children's urinary iodine ( r s = 0.21, P = 0.001) in Luyi County and adults' urinary iodine ( r s = 0.17, P < 0001) in Ningling County were positively correlated with water iodine. There was no statistically significant difference in the incidence of thyroid enlargement in children between Luyi County (0.8%, 2/240) and Ningling County (0.4%, 2/468, χ 2 = 0.80, P = 0.586), but the incidence of thyroid nodules in children in Luyi County (11.2%, 27/240) was higher than that in Ningling County (1.7%, 8/468, χ 2 = 27.36, P < 0.001). The incidence of thyroid nodules in pregnant women in Luyi County (23.3%, 28/120) was lower than that in Ningling County (46.5%, 33/71, χ 2 = 10.99, P = 0.001). There was no statistically significant difference in the incidence of adult thyroid nodules between Luyi County and Ningling County (χ 2 = 0.86, P = 0.354), with a ratio of 29.6% (71/240) to 32.9% (160/486). Conclusions:Providing population with non-iodized salt in iodine adequate areas, the overall iodine nutrition is at an appropriate level. However, children consuming iodized salt in iodine adequate areas have high level of iodine nutrition, and it is necessary to consider supplying non-iodized salt or reducing the concentration of iodized salt. Pregnant women in iodine adequate area should maintain the current policy of supplying iodized salt unchanged.

Objective:To investigate the iodine nutritional status of key populations in iodine adequate areas in Henan Province, and provide a basis for timely adoption of targeted prevention and control measures and scientific formulation of iodine supplementation strategies in iodine adequate areas.Methods:From March to September 2022, a cross-sectional survey was conducted in 60 iodine adequate counties (cities, districts) in 13 provincial-level cities in Henan Province. Administrative villages with a median water iodine level of 40 - 100 μg/L within each county (city, district) were stratified by water iodine value (40 - 49, 50 - 59, 60 - 69, 70 - 79, 80 - 89, 90 - 100 μg/L). One administrative village was selected from each water iodine layer, and 40 non boarding students aged 8 - 10 years old (age balanced, half male and half female) and 20 pregnant women were selected from each administrative village to collect their household edible salt samples and once random urine sample for test salt iodine and urinary iodine contents; and the thyroid volume of children was measured.Results:A total of 12 203 samples of household edible salt were collected from children aged 8 - 10 years old, with a median salt iodine of 24.5 mg/kg, the iodized salt coverage rate was 85.3% (10 414/12 203), and the qualified iodized salt consumption rate was 77.1% (9 406/12 203). A total of 3 999 samples of household edible salt were collected from pregnant women, with a median salt iodine of 24.0 mg/kg, the iodized salt coverage rate was 84.2% (3 366/3 999), and the qualified iodized salt consumption rate was 74.5% (2 981/3 999). A total of 12 241 urine samples from children aged 8 - 10 years old were collected, with a median urinary iodine of 290.4 μg/L. A total of 4 084 urine samples from pregnant women were collectedd, with a median urinary iodine of 233.0 μg/L. The thyroid volume of 11 971 children was examined, and the rate of goiter was 2.1% (257/11 971). Stratified by water iodine content, the median urinary iodine levels of children in 40 - 59, 60 - 79, and 80 - 100 μg/L water iodine groups were 269.7, 298.0 and 308.0 μg/L, respectively, with a statistically significant difference between the groups ( H = 67.32, P < 0.001). The goiter rates of children were 2.2% (100/4 603), 2.1% (80/3 733), 2.1% (77/3 635), respectively, with no statistically significant difference between the groups (χ 2 = 0.03, P = 0.986). The median urinary iodine levels of pregnant women were 225.4, 243.1, 234.4 μg/L, respectively, with a statistically significant difference between the groups ( H = 10.96, P = 0.004). Conclusions:The iodine nutrition level of children in iodine adequate areas in Henan Province is at an excessively suitable level, and pregnant women's iodine nutrition is at an appropriate level. It is recommended to strengthen surveillance on the basis of maintaining current prevention and control measures, and adjust prevention and control measures in a timely manner according to changes in iodine nutrition in the population.

Objective:To investigate the iodine nutritional status of children aged 8-10 years old and pregnant women in Henan Province.Methods:From March to September 2020, a cross-sectional survey was conducted in 18 provincial-level cities and 9 directly administered counties (collectively referred to as provincial-level cities) and 155 counties (cities, districts) in Henan Province. One township was selected from each county (city, district) in five directions: east, west, south, north, and central. One primary school was selected from each township, and 40 non boarding children aged 8-10 years old (half male and half female) were selected from each primary school; 20 pregnant women were selected from each township. Home edible salt samples and once urine samples from children and pregnant women were collected, to detect salt iodine and urinary iodine levels. Thyroid volume of children in 1/3 of the monitored counties (cities, districts) under the jurisdiction of each provincial-level city was examined.Results:A total of 31 645 home edible salt samples were collected from children aged 8-10 years old, with a median salt iodine of 25.8 mg/kg, the iodine salt coverage rate was 97.8% (30 941/31 645) and qualified iodine salt consumption rate was 93.4% (29 545/31 645). A total of 15 234 home edible salt samples were collected from pregnant women, with a median salt iodine of 25.7 mg/kg, the iodized salt coverage rate was 98.1% (14 937/15 234), and the qualified iodized salt consumption rate was 92.2% (14 040/15 234). A total of 31 642 urine samples from children aged 8-10 years old were tested, with a median urine iodine of 235.0 μg/L; 15 234 urine samples from pregnant women were tested, with a median urinary iodine of 196.5 μg/L. The thyroid volume of 13 792 children was examined, and the rate of goiter was 1.2% (165/13 792).Conclusions:Iodine nutrition of 8-10 years old children in Henan Province is at an over appropriate iodine level, and the prevalence of goiter is less than 5%. Pregnant women's iodine nutrition is at an appropriate iodine level.

Objective:To investigate the iodine content in drinking water of residents in Henan Province, and clarify the distribution characteristics of water iodine in Henan Province.Methods:In 2017, in all counties (cities and districts, hereinafter referred to as counties) of Henan Province, taking township (town, subdistrict office, hereinafter referred to as township) as the unit to carry out an investigation of iodine content in drinking water; and in the township with water iodine content of 10 μg/L or more, taking administrative village (neighborhood committee, hereinafter referred to as the administrative village) as the unit to carry out the drinking water iodine content investigation. Supplementary investigation was conducted from 2018 to 2020 in administrative villages where water iodine levels had never been tested or had not been tested after replacing water sources. At least 25 ml water samples were collected at each sampling site, and the water iodine content was determined by cerous sulfate catalytic spectrophotometry.Results:From 2017 to 2020, the median water iodine in Henan Province was 8.20 μg/L. A total of 50 124 administrative villages in 2 465 townships, 160 counties and 18 provincial-level cities were investigated for iodine content in drinking water, of which 65.5% (32 807/50 124) of the administrative villages had a median water iodine < 40 μg/L, belonging to iodine deficiency area; 16.9% (8 473/50 124) of the administrative villages had a median water iodine of 40-100 μg/L, suitable for iodine; and 17.6% (8 844/50 124) of the administrative villages had a median water iodine > 100 μg/L, belonging to water source high iodine area.Conclusions:Henan Province as a whole is at the state of iodine deficiency in the external environment. Most administrative villages are iodine deficiency areas. There are certain proportion of water source areas with high iodine and areas with suitable iodine.

Objective:To investigate the iodine nutritional level of residents in iodine adequate areas in Henan Province, and provide basis for making policy of targeted guidance and rational iodine supplementation.Methods:In the 156 counties of Henan Province in 2020, one township was selected from each location (east, west, south, north and middle) in each county; one school was selected from each township; 40 children aged 8-10 years in the school and 20 pregnant women in the township were selected to collect their urine and salt samples to test urine and salt iodine levels. One third of the counties were selected to examine the thyroid gland of children. Individuals lived in villages with water iodine between 40 and 100 μg/L were included in the study.Results:In iodine adequate areas, a total of 2 097 salt samples were collected from children and tested, the consumption rate of qualified iodized salt was 93.6% (1 962/2 097). A total of 2 096 urine samples were collected from children and tested, and the median urinary iodine was 288.0 μg/L. The goiter rate of children was 0.7% (5/723). A total of 1 068 salt samples from pregnant women were tested, and the consumption rate of qualified iodized salt was 93.0% (993/1 068). A total of 1 068 urine samples from pregnant women were tested, with a median urinary iodine 232.7 μg/L. Stratified by water iodine (40-59, 60-79, 80-100 μg/L), the median urinary iodine of children was 273.8, 288.6, and 305.9 μg/L, respectively, statistically significantly different between groups ( H = 15.79, P < 0.001); the goiter rate of children was ≤2%, and the difference between groups was statistically significant (χ 2 = 7.31, P = 0.026); but the median urinary iodine of pregnant women was not significantly different ( H = 1.82, P = 0.402). Under different water iodine conditions, there was no significant difference in urinary iodine levels in children and pregnant women between the high salt iodine concentration group (≥21 mg/kg) and the low salt iodine concentration group (< 21 mg/kg, P > 0.05). Conclusions:The iodine nutrition level of children in iodine adequate areas in Henan Province is relatively high, and the iodine nutrition of pregnant women is appropriate. The goiter rate of children is at a relatively low level. Continuous surveillance should be conducted to comprehensively evaluate the iodine nutrition level. Various measures will be taken by regions and populations.

Objective:To compare the coverage rate of non-iodized salts, children's iodine nutrition and the change trend of goiter rate between the original water source high iodine areas in Henan Province in 2017 and the newly designated water source high iodine areas in 2019.Methods:Using a cross-sectional survey method, household edible salt monitoring was conducted in all 20 counties (cities, districts) with high iodine content in Henan Province in 2017. Ten counties (cities, districts) were selected to monitor water iodine, urinary iodine and thyroid volume of children aged 8 to 10 years. A total of 4 430 salt samples and 1 012 urine samples were collected, and thyroid volume of 1 012 children were measured. In 2019, monitoring of household edible salt, water iodine, urinary iodine, and thyroid volume was carried out in all 55 newly designated counties (cities, districts) with high iodine village. A total of 9 835 salt samples and 9 830 urine samples were collected, and the thyroid volume of 8 896 children was measured. The monitoring results of two years were compared, and the relationship between children's urinary iodine and goiter rate was analyzed by univariate logistic regression.Results:In 2019, the water iodine content in newly designated high iodine areas decreased compared to the original high iodine areas in 2017 (119.8 to 191.0 μg/L), and the difference was statistically significant ( Z = - 2.48, P = 0.013). The rate of non-iodized salts in 2019 was only 35.5% (3 494/9 835), significantly lower than that in 2017 (96.2%, 4 263/4 430, χ 2 = 4 536.74, P < 0.001). The median urinary iodine of children in 2017 and 2019 were 338.2 and 317.8 μg/L, respectively, the difference between the two years was statistically significant ( Z = - 2.46, P = 0.014). In 2017 and 2019, the goiter rate of children aged 8 to 10 years was 1.5% (15/1 012) and 2.1% (187/8 896), respectively, and there was no significant difference between the two years (χ 2 = 1.76, P = 0.185). The results of univariate logistic regression analysis showed that, compared with the control group with urinary iodine < 100 μg/L, the risk of goiter rate (but the enlargement rate did not exceed 5%) increased with the increase of urinary iodine level (100 - 199, 200 - 299 and ≥300 μg/L groups), and the differences were statistically significant [odds ratio ( OR) = 8.64, 7.68, 10.69, P < 0.05]. Conclusion:After the implementation of the new demarcation standard for areas with excessive iodine in water sources, the supply of non-iodized salts in Henan Province is relatively lagging behind, and the iodine nutrition level of children is still high, but the goiter rate is relatively stable.

Objective:To compare the clinical effecacy of artificial dermal regeneration matrix (as "artificial dermis" hereafter) and flap transfer in the treatment of soft tissue defects around interphalangeal joint.Methods:Through postoperative follow-up at outpatient clinic, a retrospective study was conducted on the clinical data of 60 patients who had soft tissue defects around the interphalangeal joints and received treatment in the Department of Hand Surgery, the Sixth Hospital of Ningbo from January 2018 to January 2022. According to applied surgical procedures, patients were divided into a flap transfer group (group A, n=30) and an artificial dermis group (group B, n=30). Group A included 19 males and 11 females aged 44.83 years ± 11.56 years including 5 patients with simple soft tissue defects, and 6 with soft tissue defects and fractures, 10 with soft tissue defects with tendon and (or) ligament injuries, 3 with soft tissue defects and vessel and (or) nerve injuries, and 6 with soft tissue defects and over 2 other types of compound injuries. The defect areas ranged from 2.5 cm×1.2 cm to 5.0 cm×1.6 cm. After emergency debridement and treatment for bone and tendon injuries, the patients in group A received transfers of free flap or transfers with adjacent digit flaps or island flaps. Postoperative functional exercise started from 1-6 weeks after surgery. Patients in group B included 17 males and 13 females, aged 44.70 years ± 11.20 years and there were 6 patients with simple soft tissue defects, 6 with soft tissue defects and fractures, 9 with soft tissue defects and tendon and (or) ligament injuries, 5 with soft tissue defects and vessel and (or) nerve injuries, and 4 with soft tissue defects and over 2 other types of compound injuries. The defect area ranged from 3.1 cm ×1.3 cm to 4.5 cm × 1.8 cm. Debridement and treatment of the bone and tendon injury in group B were the same as what in group A, but the patients in group B received artificial dermis coverage other than transfer of flap. After an artificial dermis had completely vascularised, a split-thickness skin graft was performed over the neo-dermis in the second phase surgery. Postoperative functional exercise started from 1-2 weeks after artificial dermis grafting surgery. The interval time of flap transfer or split-thickness skin grafting, survival rate of flap transfer or split-thickness skin grafting, Vancouver Scar Scale(VSS), TPD and total active movement(TAM) were compared between the 2 groups. The count data were analysed by Chi-square test. All measured data were analysed by independent sample t test or Mann-Whitney U test. P<0.05 indicates a statistically significant difference. Results:The interval time of flap transfer in group A and artificial dermis grafting in group B were 2.93 days ± 2.48 days and 19.87 days ± 3.35 days, respectively. There was a statistically significant difference between the 2 groups( P<0.05). All patients were entered in postoperative outpatient follow-up for 11-14 months(12.00 months ± 0.93 months). The appearance of flaps of some patients in group A was bloated with slightly limited digit movement. In group B, the digit movement was normal, without obvious scar hyperplasia in both of the recipient and donor sites. The survival rate of flap transfer or artificial dermis graft, TPD, VSS score and TAM score for group A and group B were 96.00% ± 9.32% and 98.17% ± 3.07%, respectively, 8.67 mm ± 2.01 mm and 9.50 mm ± 1.81 mm, 3.40 ± 1.07 and 3.17 ± 0.91 and 18.30 ± 1.97 and 18.93 ± 1.64, respectively. There were no significant differences between the 2 groups( P>0.05). Conclusion:In comparison with the transfer of flap, an artificial dermis is also effective and satisfactory in the treatment of soft tissue defects around the interphalangeal joint. Further large scale and multi-centre investigations are required.