Ruxolitinib， a small molecule inhibitor， selectively targets Janus kinase （JAK） by competitively binding to adenosine triphosphate on the catalytic site of the JAK1 and JAK2 domain， thereby inhibiting JAK activation and signal transducer and activator of transcription （STAT） phosphorylation and prevents the expressions of the JAK-STAT signaling pathway. Oral ruxolitinib has demonstrated promising efficacy for myelofibrosis and polycythemia vera. The topical Ruxolitinib cream， approved by the US FDA as the first non-segmental vitiligo home treatment drug， is set to be launched in domestic medical pioneer areas in August 2023 and is expected to bring about a breakthrough in the treatment of vitiligo. Clinical cases have also shown that Ruxolitinib cream has significant curative effects on atopic dermatitis， alopecia areata， and other conditions， indicating great application prospects.

Objective To investigate the correlation between serum vitamin D level and central precocious puberty(CPP)in girls.Methods A total of 103 girls(case group)with central precocious puberty from Ningbo Woman and Children's Hospital and 53 healthy girls(control group)from health check-ups in Ningbo Women and Children's Hospital were collected as subjects.The serum levels of 25-hydroxyvitamin D3[25(OH)D3]in the two groups were detected by chemiluminescence method.The weight and height of girls in the case group were measured.The serum levels of follicle-stimulating hormone(FSH)and its peak value,luteinizing hormone(LH)and its peak value,estradiol(E2),prolactin(PRL),human chorionic gonadotropin(HCG)and thyroid function were measured by radioimmunoassay.The peak value of LH/FSH was calculated.B ultrasound examination of uterine adnexa was completed to calculate uterine volume and bilateral ovarian volume.According to the results of serum 25-(OH)D3,girls in the case group were divided into normal vitamin D group and vitamin D deficiency group,and the differences of hormone levels,uterine and ovarian development between the two groups were compared.Results The serum level of 25-(OH)D3 in case group was lower than that in control group,and the vitamin D deficiency rate in case group was higher than that in control group,with statistical significance(P<0.05).The age of breast nodules in vitamin D deficiency group was lower than that in vitamin D normal group(P<0.05).There were no significant differences in body weight,height,body mass index(BMI),uterine volume and left ovarian volume between vitamin D normal group and vitamin D deficiency group(P>0.05),and the right ovarian volume in vitamin D deficiency group was significantly higher than that in vitamin D normal group(P<0.05).There were no significant differences in serum levels of FSH,LH,PRL,HCG,peak value of FSH and thyroid function between normal and deficient groups(P>0.05).The levels of E2,LH and LH/FSH in vitamin D deficiency group were significantly higher than those in vitamin D normal group(P<0.05);25-(OH)D3 was negatively correlated with LH/FSH peak(r=-0.197,P<0.05),but was not significantly correlated with thyroid function,FSH,LH,PRL,E2,HCG,FSH and LH peak(P>0.05).Conclusion Vitamin D deficiency is associated with central precocious puberty in girls.Vitamin D deficiency may lead to early onset of precocious puberty.Vitamin D deficiency may affect the hypothalamic-pituitary-gonadal axis function,resulting in changes in reproductive hormone indexes and consequent increase in ovarian volume in girls.

Objective:To follow up the iodine nutrition and intellectual development of school children aged 8-10 years old in Nangqian County of Qinghai Province after 9 years of the implementation of iodine deficiency disorders intervention measures with iodine supplement as the main measure.Methods:In order to improve the iodine nutritional status of the population in Nangqian County, free iodized salt distribution, health education and other intervention measures for iodine deficiency disorders were implemented for 9 consecutive years since 2013. In May 2012 (before iodine supplementation) and September 2021 (after iodine supplementation), the same 5 townships (towns) were selected, and children aged 8-10 years old (half male and half female, age balanced) born locally in the central primary school of each township (town) were selected as the survey subjects. Household edible salt samples and random urine samples were collected for salt iodine and urinary iodine detection; the second revised version of the Chinese Combined Raven's Test (rural version) was used to assess the intelligence quotient (IQ) of children. The Flynn effect (FE) gain was used to adjust IQ, the corrected IQ = (IQ starting point value - current year's IQ value) - FE gain (calculated by 0.74/year). The differences of salt iodine and urinary iodine related indexes, IQ value and corrected IQ were compared before and after iodine supplementation.Results:After iodine supplementation, the coverage rate of iodized salt reached 100.00% (300/300), and the consumption rate of qualified iodized salt reached95.00% (285/300), the median urinary iodine increased to 157.20 μg/L, and all indexes met the elimination standard of iodine deficiency disorders. The IQ value of children aged 8-10 years old after iodine supplementation was 99.00 ± 14.90, significantly higher than that before iodine supplementation (82.00 ± 13.20, F = 156.82, P < 0.001). The FE gain in 9 years was 6.66, and the actual IQ gain of children aged 8-10 years old after iodine supplementation was 10.34. There were statistically significant differences in IQ value before and after iodine supplementation in male and female children ( F = 78.84, 78.88, P < 0.001). After iodine supplementation, there was a statistically significant difference in IQ value between children in the 8-year-old group and the 10-year-old group ( P = 0.010). There were statistically significant differences in IQ value before and after iodine supplementation in 8, 9 and 10 years old groups ( F = 55.23, 65.79, 36.85, P < 0.001). Conclusion:Intervention measures for iodine deficiency disorders, mainly iodine supplement, can significantly improve the iodine nutrition status of children aged 8-10 years old, and significantly promote the intellectual development of children.

Objective:To analyze the external quality control assessment results of urinary iodine, salt iodine and water iodine in iodine deficiency disorders laboratories in Qinghai Province, to evaluate the testing capacity of provincial, municipal and county-level laboratories and the operation of external quality control network, so as to provide quality assurance for consolidating and eliminating iodine deficiency disorders.Methods:In 2021, 1 provincial, 8 municipal, and 43 county-level laboratories in Qinghai Province had participated in the assessment of urinary iodine and salt iodine, while 1 provincial and 8 municipal-level laboratories had participated in the assessment of water iodine. The assessment results were evaluated using the method of reference value ± uncertainty of external quality control samples.Results:All laboratories that participated in the assessment had provided feedback. One provincial-level laboratory passed the assessment of urinary iodine, salt iodine, and water iodine. Among 8 municipal-level laboratories, 2 laboratories failed the urinary iodine assessment, with a pass rate of 6/8; the assessment of salt iodine and water iodine in 8 laboratories were all qualified. Among 43 county-level laboratories, 7 laboratories failed the urinary iodine assessment, with a pass rate of 83.7% (36/43); the assessment of salt iodine in 43 laboratories were all qualified.Conclusions:The external quality control network of iodine deficiency disorders laboratories in Qinghai Province has fully covered all municipal and county-level laboratories. The testing capability of provincial-level laboratory is stable and maintains a high level; the testing quality of some municipal and county-level laboratories is still unstable and needs to be further strengthened.

Objective:To investigate the clinical characteristics, diagnosis and treatment of dermatomyositis with kidney neoplasm.Methods:The data of two patients with dermatomyositis complicated with kidney neoplasm in Tongji Hospital from January to February 2022 were retrospectively analyzed. The first case was a 55-year-old female, who was admitted with the chief complaints of recurrent erythema of upper extremities for 2 months and facial erythema for 1 month. Physical examination: erythema can be seen on upper limbs and face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Mi-2 antibody and anti-SSA /Ro-52 antibody were positive. Contrast CT showed nodular uneven enhancement in the right kidney with a size of 50 mm×41 mm. The second case was a 58-year-old female, who was admitted with the chief complaints of kidney occupying for a month. Physical examination: flaky erythema on face, no tenderness or percussion pain in kidney area. Myositis enzyme profile test showed that anti-Ro-52 antibody and anti-MDA5 antibody were positive. Contrast CT showed a significantly uneven enhanced mass with a size of about 50 mm×41 mm on left kidney. Both patients were diagnosed with kidney neoplasm before surgery and underwent laparoscopic partial nephrectomy in Tongji Hospital.Results:Both patients received regular oral prednisone after surgery. The pathological presentation of case 1 was papillary renal cell carcinoma, the facial erythema subsided 1 month after surgery, and there was no tumor recurrence for 13 months. The pathological presentation of case 2 was clear cell renal cell carcinoma, facial erythema subsided 2 weeks after surgery, and there was no tumor recurrence for 12 months.Conclusions:The diagnosis of dermatomyositis should be combined with clinical manifestations and laboratory examination, and the possibility of malignant tumor should be excluded due to the high likelihood of concomitant malignancy. For patients with dermatomyositis with kidney neoplasm, the main treatment is still surgery, and supplemented with glucocorticoid therapy.

Objective:To investigate the molecular mechanism of excessive iodine induced experimental autoimmune thyroiditis (EAT) in mice.Methods:Sixty female non-obese diabetic (NOD) mice were selected and divided into 5 groups according to body weight [(25 ± 3) g] via the random number table method, with 12 mice in each group: control group (group A), 10-fold high iodine group (group B), 100-fold high iodine group (group C), 1 000-fold high iodine group (group D) and 1 000-fold high iodine combined with polyinosinic acid-polycytidylic acid [Poly (I:C)] group (group E). The experiment period was 16 weeks. Mice in each group drank purified water with sodium iodine (NaI) content of 0.000, 0.005, 0.050, 0.500 and 0.500 mg/L, respectively; mice in group E were intraperitoneally injected with Poly (I:C) at week 7 and week 15, respectively. At the end of the 16th week, mice were dissected and blood samples and thyroid tissue were taken. The levels of serum thyroid function indexes [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), and thyroid peroxidase antibody (TPOAb)] were detected by enzyme-linked immunosorbent assay (ELISA); the pathological changes of thyroid tissue were observed after hematoxylin-eosin (HE) staining; differentially expressed genes in thyroid tissue were detected by RNA-sequencing (RNA-seq), and analyzed by KEGG pathway; mRNA and protein levels of p38, intercellular adhesion molecule-1 (ICAM-1) and chemokine 10 (CXCL10) in thyroid tissue were detected by real-time fluorescence quantitative PCR (qPCR) and Western blotting, respectively. Results:There were statistically significant differences in serum levels of TSH (ng/ml: 6.53 ± 0.86, 6.61 ± 0.82, 7.68 ± 0.55, 7.93 ± 0.60, 8.73 ± 1.60), FT 3 (pg/ml: 59.35 ± 10.16, 53.73 ± 10.96, 46.19 ± 8.03, 41.01 ± 8.67, 34.21 ± 11.75), FT 4 (pg/ml: 136.74 ± 10.06, 124.33 ± 14.34, 101.80 ± 6.78, 91.37 ± 6.75, 73.29 ± 17.31), and TPOAb (U/ml: 130.81 ± 24.53, 145.47 ± 28.89, 166.52 ± 41.59, 199.78 ± 42.19, 201.99 ± 44.03) among the 5 groups of mice ( F = 4.77, 4.96, 23.12, 3.68, P < 0.05). Compared with group A, the serum TSH levels of mice in groups C, D and E were higher, the levels of FT 3 and FT 4 in groups B, C, D and E were lower, and the levels of TPOAb in groups D and E were higher, and the differences were statistically significant ( P < 0.05). HE staining showed that the thyroid follicle lesion in groups D and E was serious, and the EAT phenotype appeared in both groups. The differentially expressed genes were analyzed by KEGG pathway. Compared with group A, 8 metabolic pathways related to thyroid autoimmunity and inflammation were found in groups B, C, D and E. Further analysis found that 3 genes appeared in multiple pathways, namely p38, ICAM-1 and CXCL10. There were significant differences in the mRNA levels of p38, ICAM-1 and CXCL10 in thyroid tissue of the 5 groups of mice ( F = 14.77, 12.76, 16.39, P < 0.05); compared with group A, the mRNA levels of p38 in groups B, C, D and E were higher, and the mRNA levels of ICAM-1 and CXCL10 in groups C, D and E were higher ( P < 0.05). There were significant differences in the protein levels of p38, ICAM-1 and CXCL10 in thyroid tissue of the 5 groups of mice ( F = 7.97, 73.86, 18.02, P < 0.05); compared with group A, the protein levels of ICAM-1 and CXCL10 in groups B, C, D and E were higher ( P < 0.05). Conclusion:Excessive iodine promotes the occurrence and development of EAT in mice by up-regulating the expressions of p38 and ICAM-1 genes that are closely related to thyroid autoimmune and inflammatory responses.

Objective:To investigate the dietary iodine intake of people in different areas of Qinghai Province, and to provide the basis for scientific iodine supplementation and continuous elimination of iodine deficiency hazards.Methods:From 2018 to 2019, according to administrative division, natural geographical regions, population distribution and economic development level of Qinghai Province, a total of 14 survey sites were selected. One village was selected from each survey site, and 20 households were selected from each village, the salt samples and 24 h urine samples of all family members were collected to detect salt iodine and urinary iodine. One drinking water sample was collected at the five directions of east, west, south, north and middle of each village to detect water iodine. Salt iodine was detected by direct titration, urinary iodine and water iodine were detected by arsenic-cerium catalytic spectrophotometry. At the same time, the 3-day weighing method was used to investigate the diet, the daily dietary iodine intake per capita (the result was expressed as average) and the proportion of dietary iodine in urinary iodine were calculated, the daily dietary iodine intake per capita of different production modes (agricultural region and pastoral region), different geographical environment (Hehuang Valley, Qaidam Basin, Qilian Mountain and Qingnan Plateau), different nationalities (Han, Tibetan, Hui, Mongolian, Tu, Salar) and different economic levels (< 8 000, 8 000 -, 10 000 -, ≥12 000 Yuan) were compared.Results:A total of 999 people from 280 families were surveyed, including 511 males and 488 females. The median water iodine of each survey site was less than 10 μg/L, all of which were environmentally iodine-deficient areas. A total of 280 salt samples were collected, the median salt iodine was 26.0 mg/kg, and the consumption rate of qualified iodized salt was 100% (280/280). A total of 999 urine samples were tested, and the median urinary iodine of people was 192.5 μg/L, which was at an appropriate level of iodine. There was no statistically significant difference ( t =-1.599, P > 0.05) in the daily dietary iodine intake per capita (28.53, 33.44 μg) of people in agricultural region ( n = 643) and pastoral region ( n = 356). The daily dietary iodine intake per capita (25.38, 33.30, 32.98, 34.79 μg) of people in Hehuang Valley ( n = 448), Qaidam Basin ( n = 125), Qilian Mountain ( n = 157), and Qingnan Plateau ( n = 269) were compared, the difference was statistically significant ( F = 2.883, P < 0.05); among them, the daily dietary iodine intake per capita in Hehuang Valley was lower than that in Qingnan Plateau ( P < 0.05). The daily dietary iodine intake per capita of different nationalities were compared, the difference was statistically significant ( F = 3.647, P < 0.05), Salar ( n = 68) and Tibetan ( n = 239) were higher (37.21 and 32.21 μg). The daily dietary iodine intake per capita (38.97, 17.01, 30.86, 33.14 μg) of annual per capita disposable income < 8 000 ( n = 194), 8 000-( n = 221), 10 000-( n = 302), ≥12 000 Yuan ( n = 282) were compared, the difference was statistically significant ( F = 9.407, P < 0.05). The proportions of dietary iodine in urinary iodine of various population ranged from 5.35% to 15.54%. Conclusions:The iodine nutrition of people in Qinghai Province is suitable, the dietary iodine intake of people is closely related to geographical environment, nationality and economic level. But the proportion of dietary iodine in urinary iodine is relatively low, the consumption of iodized salt is still the main way for people to intake iodine, and it is also the main measure to continuously eliminate the harm of iodine deficiency in Qinghai Province.

Objective:To understand the water iodine content in Qinghai Province and draw a distribution map of water iodine, so as to provide a basis for scientific supplementation of iodine and continuous elimination of iodine deficiency hazards.Methods:In 2017, in all counties (cities, districts) in Qinghai Province, with townships (towns, streets, referred to as townships) as the unit, the residents' drinking water samples were collected, water iodine content was tested, the median water iodine was calculated, and the water iodine distribution map of Qinghai Province was drew.Results:Totally 1 836 drinking water samples were collected in 392 townships, the median water iodine was 1.7 μg/L. Townships that had the median water iodine < 5 μg/L, in the range of 5 to 10 μg/L and > 10 μg/L accounted for 80.6% (316/392), 17.1% (67/392) and 2.3% (9/392), respectively. Among all townships, the highest of the median water iodine was 24.8 μg/L. Based on the results, water iodine distribution map of Qinghai Province, water iodine distribution map of Xining City and water iodine distribution map of Haidong City were compiled.Conclusions:Iodine deficiency is widespread throughout natural environment in Qinghai Province. Hence, salt iodization measures to prevent iodine deficiency disorders should be implemented continuously. According to the water iodine distribution map, the people should be guided to supplement iodine scientifically.

Objective To summarize the preliminary experience of extraperitoneal laparoscopic radical prostatectomy (C.R.P.C.four-step) for localized prostate cancer and the outcomes based on early follow-up.Methods A total of 102 prostate cancer patients were screened by prostate specific antigen (PSA) and diagnosed by prostate magnetic resonance imaging and prostatic puncture biopsy with cT1c-cT3b,with average age of (67 ±5) years old,average preoperative total PSA value of (45.32 ± 18.33) ng/ml,and average prostate volume was (42 ± 12)cm3.All these patients underwent extraperitoneal laparoscopic radical prostatectomy by the four-step technique,abbreviating as C.R.P.C.[C:control DVC (dorsal deep venous complex).R:recognize three anatomical layers (prostate and bladder junction,seminal vesicle,and Denonvilliers' fascia surface).P:preserve urethral sphincter and bladder neck.C:continuous anastomosis between urethra and bladder neck (4 key needles at 3,5,7 and 9 o'clock)].The operative time,estimated blood loss,length of hospital stay and postoperative complications were recorded,and the postoperative PSA was followed up.Results All the 102 cases were successfully treated by iaparoscopic radical prostatectomy.The operative time was from 55 to 156 min (mean 92 min),and the estimated blood loss was from 55 to 185 ml (mean 105 ml).There was no case converted of open surgery,only one case received blood transfusion for postoperative hemorrhage (0.98％),and positive surgical margin was found in 15 case (14.70％) by pathological examination.Postoperative urinary extravasation within one week occurred in 2 (1.96％) cases,and resolved after tensioning the catheter and prolonging the indwelling time.During the follow-up period of 12 to 45 months,2 cases were incontinent (grade I-II),and the other cases(98.04％) had no incontinence or dysuria.However,11 cases (10.78％) developed to biochemical recurrence within 6 months after the operation.Conclusions The C.R.P.C.four-step technique of lparoscopic radical prostatectomy is easily to be grasped and performed by the greenhand urologists,and was efficient and safe.

Objective:To analyze the assessment results of the external quality control in iodine deficiency disorders laboratories at all levels in Qinghai Province so as to provide quality assurance for monitoring and control effect evaluation of iodine deficiency disorders.Methods:The results of urinary iodine, salt iodine, and water iodine quality control assessments at the provincial, city (state) and county-level iodine deficiency disorders laboratories were analyzed in Qinghai Province from 2013 to 2018 (sourced from the annual evaluation results issued by National Reference Laboratory for Iodine Deficiency Disorders). Among them, there were 1 provincial, 8 city (state) and 43 county-level (2017, 2018) laboratories participated in the urinary iodine assessment; 1 provincial, 8 city (state) and 30 county-level (43 in 2017 and 2018) laboratories participated in the salt iodine assessment; 1 provincial and 8 city (state)-level laboratories participated in the water iodine assessment.Results:From 2013 to 2018, the feedback rates and qualified rates of provincial and city (state)-level laboratories participated in the urinary iodine external quality control assessment were 100.0%; the feedback rates of 43 county-level laboratories (2017 and 2018) were 100.0%, and the qualified rates were 93.0%(40/43) and 88.4%(38/43), respectively. The feedback rates and qualified rates for salt iodine assessment in provincial and city (state)-level laboratories were 100.0%; the county-level laboratories feedback rates were 100.0%, and the qualified rates were > 90.0% except for 2014. And the feedback rates of provincial and city (state)-level laboratories for water iodine assessment were 100.0%; the qualified rate of provincial-level laboratory was 100.0%, and the city (state)-level laboratories were 100.0% except 2016 (7/8).Conclusions:The quality control network of Qinghai Province's iodine deficiency disorders laboratories has fully covered all city (state) and county-level laboratories. Provincial, city (state)-level laboratories have stable and reliable levels of urinary iodine, salt iodine, and water iodine; some individual county-level laboratories testing capabilities still need to be improved.