OBJECTIVE: To investigate the association between SPAG17 gene variant and Familial severe asthenozoospermia, and to assess its impact on the outcome of intracytoplasmic sperm injection (ICSI). METHODS: Two siblings (Probands 1 and 2) with severe asthenozoospermia from a Chinese family who presented at the Reproductive Medicine Center II of Gansu Maternity and Child Health Care Hospital (Gansu Provincial Central Hospital) in May 2023 were selected as study subjects. Clinical data were collected, and sperm morphology and ultrastructure (assessed by transmission electron microscopy) were analyzed. Pathogenic variants were screened using whole exome sequencing (WES) and verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of Gansu Maternity and Child Health Care Hospital (Ethics No.: 2023GSFYLS78). RESULTS: Probands 1 and 2 had primary infertility for 10 and 3 years, respectively, and both exhibited normal semen concentration, but the percentage of progressive motile sperm (PR) was significantly lower than the normal reference value (> 32.00%), measuring 2.33% ± 0.58% and 0.80% ± 0.45%, respectively. Additionally, the percentage of sperms with normal morphology was slightly below the reference range (> 4.00%), with the values of 3.36% ± 0.35% and 2.93% ± 1.36%. Both probands were found to harbor homozygous c.2188C>T (p.Q730*) nonsense variant of the SPAG17 gene (NM_206996.4), for which their mother was a heterozygous carrier (their father had already deceased). Both sibs underwent ICSI treatment using a long gonadotropin-releasing hormone agonist protocol during the follicular phase combined with assisted oocyte activation (AOA). The wife of Proband 1 ultimately gave birth to a healthy girl, whilst the wife of Proband 2 delivered two healthy girls. CONCLUSION The homozygous c.2188C>T (p.Q730*) nonsense variant of the SPAG17 gene is closely related with the severe asthenozoospermia phenotype. Live births can be achieved through ICSI combined with AOA technology, though the overall utilizable embryo rate may be relatively low.
Humans ; Male ; Asthenozoospermia/genetics* ; Adult ; Sperm Injections, Intracytoplasmic ; Pedigree ; Spermatozoa ; Female ; Exome Sequencing

Objective:To analyze the iodine nutrition status of key populations in water source high iodine areas in Jiangsu Province, providing a reference for scientific prevention and control of water source high iodine hazards.Methods:From May to June 2020, monitoring sites were determined by administrative villages in six high iodine counties (cities, districts) in Jiangsu Province, and drinking water samples were collected from residents to detect the iodine content in the water; 40 non boarding children aged 8 - 10 from one primary school in each village (half male and half female, with an age balance) and 20 pregnant women were selected. Salt samples were taken from children and pregnant women's homes, and urine samples were randomly taken once to detect salt and urine iodine contents. Thyroid volume of children was examined.Results:A total of 36 administrative villages were monitored, with a median of 45.3 μg/L for water iodine, ranging from 8.5 - 372.1 μg/L. A total of 1 422 salt samples were collected, of which 26 were iodized salt, accounting for 1.83%; and 1 396 non iodized salt, with the coverage rate of non iodized salt was 98.17%. A total of 1 365 urine samples were collected from children, with a median urine iodine of 405.6 μg/L. There were statistically significant differences in urine iodine levels among children in different regions, drinking water iodine contents, and age groups ( H = 128.39, 67.81, 39.94, P < 0.001). A total of 57 urine samples were collected from pregnant women, with a median urine iodine of 282.0 μg/L. There were statistically significant differences in urine iodine levels among pregnant women in different regions and drinking water iodine contents groups ( H = 17.54, 18.39, P < 0.001). A total of 1 365 children's thyroid volumes were examined, and 44 cases of thyroid enlargement were detected, with a goiter rate of 3.22%. There were no statistically significant differences in the incidence of thyroid enlargement among children in different regions, drinking water iodine contents, salt types, gender, and age groups ( P > 0.05). Conclusions:The iodine nutrition of children in water source high iodine areas in Jiangsu Province is at an iodine excess level, while the iodine nutrition of pregnant women is at an over optimal level. In areas with high iodine content in water sources, the iodine content in drinking water has a significant impact on the iodine intake of the local population. There is currently no correlation between the iodine content in drinking water, salt type, gender, and age factors and thyroid enlargement in children.

Objective:To learn about the implementation of prevention and control measures in drinking water-borne endemic fluorosis areas and the trend of the disease change in Jiangsu Province.Methods:In March to October 2021, a general survey was carried out in 1 972 villages with drinking water-borne endemic fluorosis in 27 counties (cities and districts) of Jiangsu Province, the operation of water improvement projects in the villages was monitored, and the water fluoride content was determined. The prevalence of dental fluorosis among children aged 8 to 12 years in all the villages was investigated.Results:The 1 972 villages with drinking water-borne endemic fluorosis had completed water improvement, and all water improvement projects were operating normally and the water was qualified. Among them, 1 774 villages in the disease affected areas had achieved the control goal, accounting for 89.96%; and there were 198 villages in the disease affected areas with control measures up to the standard, accounting for 10.04%. A total of 47 water improvement projects were monitored, including 2 small-scale water improvement projects, accounting for 4.26%. There were 45 large-scale water improvement projects, accounting for 95.74%. A total of 125 790 children aged 8 to 12 years were examined, and 12 625 cases of dental fluorosis were detected. The detection rate of dental fluorosis was 10.04%, and the dental fluorosis index was 0.19. The detection rate of dental fluorosis in children aged 8 to 12 years was 9.98% (1 854/18 579), 10.27% (2 704/26 323), 9.48% (2 765/29 152), 9.73% (2 835/29 145) and 10.92% (2 467/22 591), respectively, with statistically significant difference (χ 2 = 10.51, P = 0.015). Among the 198 villages with control measures up to standard, according to the historical water fluoride, the detection rate of dental fluorosis in children in each water fluoride range (1.20-2.00, 2.01-3.00, 3.01-4.00, > 4.00 mg/L) was 37.73% (698/1 850), 43.17% (1 176/2 724), 45.50% (769/1 690) and 55.20% (802/1 453), respectively, with a statistically significant difference (χ 2 = 104.15, P < 0.001). Conclusion:The water improvement measures in drinking water-borne endemic fluorosis areas in Jiangsu Province have achieved significant results, which still need to be further consolidated.

Objective:To dynamically observe the changes in iodine level in residents' drinking water after the change of regional water supply mode (2020) in Jiangsu Province.Methods:The survey of water iodine level was conducted from June to October 2020 in administrative villages of Jiangsu Province with a median water iodine ≥40 μg/L in 2017. The survey mainly covered 1 537 administrative villages in 21 counties (cities and districts) of 5 cities, including Huaian City, Lianyungang City, Suqian City, Yancheng City, and Xuzhou City. Based on the standard of "Definition and Demarcation of Iodine Deficient Areas and Iodine Adequate Areas" (WS/T 669-2020), the administrative villages with a median water iodine of 40 - 100 μg/L were classified as iodine adequate areas. Water iodine testing was conducted using the "Method for Water Iodine Testing in Iodine Deficient and High Iodine Areas" recommended by the National Reference Laboratory for Iodine Deficiency Disorders.Results:Totally 1 498 administrative villages in Jiangsu Province were monitored in 2020, all of which had centralized water supply. The minimum value of water iodine in all administrative villages was 1.2 μg/L and the maximum value was 606.7 μg/L, and the median water iodine was 35.2 μg/L. Among them, 206 administrative villages had median water iodine < 10 μg/L, accounting for 13.75% (206/1 498); 610 administrative villages had median water iodine from 10 to < 40 μg/L, accounting for 40.72% (610/1 498); 635 administrative villages had median water iodine from 40 to 100 μg/L, accounting for 42.39% (635/1 498); and 47 administrative villages with median water iodine > 100 μg/L, accounting for 3.14% (47/1 498). Except for Sucheng District in Suqian City, Xinyi City and Gulou District in Xuzhou City, Qingjiangpu District and Xuyi County in Huaian City, and Guannan County in Lianyungang City, the median water iodine in the administrative villages of the remaining 15 counties (cities and districts) in 2020 decreased significantly compared to 2017, and the differences were statistically significant ( P < 0.05). Conclusion:After change of regional water supply mode in 2020, in most monitored counties (cities and districts) of Jiangsu Province, the water iodine level of administrative villages has decreased significantly compared to 2017.

Objective:To analyze the detection rate of thyroid nodules and goiter in school-age children in different water iodine regions and investigate the difference of thyroid nodule and goiter in school-age children with different age, gender and body mass index (BMI) in Jiangsu Province.Methods:In 2017, three villages with water iodine values of 8.1, 51.2 and 115.4 μg/L (iodine deficient group, iodine appropriate group and iodine high group) were selected as survey sites in Xuzhou City, Jiangsu Province, where the supply of iodized salt was suspended. One primary school was selected from each village, and children aged 8 to 10 years old (age balance, half male and half female) were selected from each primary school as the survey subjects. Urine sample were collected, urinary iodine level was determined, height and weight were measured, and neck B ultrasound was performed.Results:A total of 131, 140 and 138 school-age children aged 8 to 10 years old were investigated in the iodine deficient group, iodine appropriate group and iodine high group, respectively, with a total of 409 children. The detection rates of thyroid nodules were 6.9% (9/131), 15.0% (21/140) and 16.7% (23/138), respectively, and the detection rates of goiter were 1.5% (2/131), 1.4% (2/140) and 6.5% (9/138) in the three groups, respectively. There were statistically significant differences in the detection rates of thyroid nodules and goiter in different water iodine groups (χ 2 = 6.92, 6.37, P < 0.05). The detection rates of thyroid nodules in different age groups were 9.5% (12/126), 11.3% (16/142) and 17.7% (25/141), the differences were statistically significant (χ 2 = 9.05, P < 0.05). The detection rates of thyroid nodules were 11.6% (24/207), 14.4% (29/202), and 12.5% (39/313), 16.9% (14/83), 0/9 and 0/4 in the subjects of different gender and BMI, the differences were not statistically significant (χ 2 = 0.69, P > 0.05). The detection rates of goiter in the subjects of different gender, age and BMI were 1.4% (3/207), 5.0% (10/202); 2.4% (3/126), 6.3% (9/142), 0.7% (1/141); 1.6% (3/313), 4.8% (4/83), 3/9 and 1/4. The differences were statistically significant (χ 2 = 4.07, 7.66, P < 0.05). Conclusion:The detection rate of thyroid nodules in school-age children in different water iodine regions in Jiangsu Province may have a certain relationship with age, and the detection rate of goiter may have a certain relationship with age, gender and BMI.

Objective:To evaluate the effect of health education on drinking-warter-borne endemic fluorosis in Jiangsu Province.Methods:From 2014 to 2018, a total of 12 counties (districts) with drinking-warter-borne endemic fluorosis were selected to carry out public health education activities, and 3 townships were chosen in each project county (district). School health education activities were carried out in the classes of grade 4 - 6 in the central primary school in each selected twonship. In the meantime, 3 villages were chosen in each selected township where the health education activities in the community were carried out. Before and after the health education activities, questionnaire surveys on knowledge of drinking-warter-borne endemic fluorosis prevention were conducted among 30 students in one class of grade 5 in the central primary school and 15 housewives lived near the central primary school in each township.Results:After the health education activities, the rates of knowledge awareness in the students and the housewives were 94.83% (15 362/16 200) and 95.14% (7 706/8 100), respectively, which were significantly higher than those before the health education activities [63.88% (10 348/16 200) and 65.94% (5 341/8 100)], and the differences were statistically significant (χ 2 = 4 700.00, 2 200.00, P < 0.001). There were no statistical differences in the rates of knowledge awareness in the students and housewives before the health education activities from 2014 to 2018 (χ 2 = 8.43, 0.88, P = 0.077, 0.928). Before the health education activities, the rate of knowledge awareness in the students was lower than that in the housewives, and the difference was statistically significant (χ 2 = 10.03, P = 0.002). After the health education activities, there was no statistical difference between the rate of knowledge awareness in the students and that in the housewives (χ 2 = 1.07, P = 0.301). Conclusions:The rates of knowledge awareness in the students and the housewives are increased significantly after the health education activities. We should expand the coverage of health education. Wide, deep and persistent health education in more ways for different people are needed to consolidate the achievements.

Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate

Objective:To investigate the iodine content distribution of drinking water in Jiangsu Province.Methods:In 2017, the iodine content in drinking water of residents in townships (streets, hereinafter referred to as townships) of Jiangsu Province was investigated. Administrative villages (neighborhood committees, hereinafter referred to as administrative villages) of Jiangsu Province were selected as units for the investigation of townships with the median water iodine greater than 10 μg/L. Delimitation criteria: the median iodine content of water < 40 μg/L was iodine deficiency area, 40-100 μg/L was suitable iodine area, and > 100 μg/L was high iodine area.Results:A total of 1 285 townships were surveyed in 101 counties (cities, districts) in 13 cities, and the median water iodine in townships was 7.28 μg/L. Among them, there were 875 townships with median water iodine < 10 μg/L, accounting for 68.09%; 315 townships 10-< 40 μg/L, accounting for 24.51%; 56 townships 40-100 μg/L, accounting for 4.36%; 39 townships > 100 μg/L, accounting for 3.04%. The water iodine survey at the administrative village level was conducted in 5 864 administrative villages in 410 townships in 6 cities. Among them, 769 administrative villages with median water iodine < 10 μg/L, accounting for 13.11%; 3 558 administrative villages 10 - < 40 μg/L, accounting for 60.68%; 613 administrative villages 40 - 100 μg/L, accounting for 10.45%; and 924 administrative villages > 100 μg/L, accounting for 15.76%.Conclusion:According to the water iodine, there are iodine deficiency, suitable iodine and high iodine areas in Jiangsu Province, mainly in iodine deficiency areas.

Objective To further understand and master the distribution and influencing factors of water iodine in Jiangsu Province.Methods From 2012 to 2014,half of the water plants in rural centralized water supply monitoring plants in 63 counties (cities,districts) of Jiangsu Province were selected as survey sites,and the types of monitoring,types of water plants,types of water sources,self-inspection ability,disinfection situation,water treatment methods were investigated and analyzed.One sample of peripheral water was collected from each survey site to determine the water iodine content.Results From 2012-2014,there were 938 samples of river water were monitored,and the median water iodine was 5.9 μg/L.There were 57 samples of lake water were monitored,the median water iodine was 6.8 μg/L.There were 228 samples of reservoir water were monitored,and the median water iodine was 7.1 μg/L.There were 43 samples of gully pond water were monitored,and the median water iodine was 6.9 μg/L.There were 5 474 samples of deep well water were monitored,and the median water iodine was 28.2 μg/L.There were 162 samples of shallow well water were monitored,and the median water iodine was 30.9 μg/L.There was a statistically significant difference in the median iodine content of water samples from different water sources (x2 =844.9,P ＜ 0.05).The differences of median iodine of lake water,reservoir water,gully pond water,deep well water and shallow well water among different monitoring types were significant (x2 =9.6,6.3,9.7,121.2,38.1,P ＜ 0.05).The differences of median iodine of river water,reservoir water,deep well water and shallow well water among different types of water plants were significant (x2 =109.5,39.0,153.3,7.6,P ＜ 0.05).The iodine contents of fiver water,lake water,deep well water and shallow well water had significant difference in selfinspection ability of different water plants (x2 =62.5,5.1,29.9,10.1,P ＜ 0.05).The iodine content of reservoir water,deep well water and shallow well water were significandy different in different disinfection situation (x2 =12.1,12.4,35.7,P ＜ 0.05).The medians iodine of river water,reservoir water,deep well water and shallow well water had significant difference in different water treatment methods (x2 =9.5,21.2,102.4,46.9,P ＜ 0.05).Conclusions The water iodine contents of water samples in different types of water sources in rural area of Jiangsu Province are different.The level of water iodine is affected by factors such as monitoring type,type of water plant,self-inspection ability,disinfection situation and water treatment method.

Objective To understand the drinking water type fluorosis in Jiangsu Province, dynamically monitor the disease trends, and to evaluate the operation effect of the water project comprehensively. Methods Twenty-six fluorosis districts and counties in Xuzhou, Lianyungang, Suqian, Huaian and Yancheng were selected as the monitoring sites. The change of water improvement engineering and the value of water fluoride were surveyed and tested. There were three different situations of changed water: the water improvement engineering operated normally was the first, the water improvement engineering operated abnormally or water fluorine excesses the standard was the second,and without water improvement was the last.The teeth of children aged 8 to 12 years were checked according to the method of Dean. The skeletal fluorosis of adults was checked according to "Diagnostic Criteria of Endemic Skeletal Fluorosis"(WS 192-2008) by X-ray inspection. Results The normal operation rates of changed water project from 2011 to 2015 were 100.00% (30/30), 85.29% (29/34), 82.50% (33/40), 95.92% (47/49),and 97.83%(45/46),and the excessive rates of water fluorosis for normal operating engineering were 13.33%(4/30),17.24%(5/29),9.09%(3/33),14.89%(7/47),and 11.11%(5/45).The dental fluorosis detection rates of children aged 8 to 12 years were 33.68% (194/576), 28.30% (711/2 512), 36.25% (1 577/4 350), 22.06% (837/3 794), and 20.44% (903/4 417) from 2011 to 2015, the differences were statistically significant (χ2= 190.952, P < 0.05). The dental fluorosis detection rates in the three situations of water changed annually was statistically significant (χ2=129.336, 130.402, 21.419, P < 0.05). The detection rates between three different water conditions were 21.88% (2 857/13 057), 57.23% (1 156/2 020), 36.54%(209/572), and the differences were statistically significant (χ2=206.295, P < 0.05). Differences between the villages with water improvement engineering changed but not worked and the villages with water improvement engineering changed and worked well and the villages without the water improvement engineering were statistically significant(χ2=200.861,36.336,P<0.0125).The difference of detection rates between the villages with normal operation and the villages without water improvement was not statistically significant(χ2=2.131, P>0.0125).The X-ray detection rates of skeletal fluorosis in adults from 2011-2015 were 17.83% (51/286), 16.61% (49/295), 15.36% (51/332), 10.95% (53/484), and 5.16% (16/310); urinary fluoride range was 0.02 - 22.0 mg/L; the geometric average was 0.67 - 4.06 mg/L, there was no statistical significant difference of skeletal fluorosis distribution annually(χ2=6.060, P > 0.05). Conclusion The general condition of drinking water type fluorosis in Jiangsu Province from 2011 to 2015 is gradually under control, but the engineering operation and water quality improvement still need to be improved; water change project not functioning or with excess fluorine is more harmful to children's teeth.