A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

A UHPLC-Q-Orbitrap/MS method was developed to identify the related substances in apixaban tablets. Complete separation was accomplished with a Waters Xbridge C18 (250 mm×4.6 mm, 5 μm) column by linear gradient elution using a mobile phase consisting of 30 mmol/L ammonium acetate buffer solution (pH 4.50) and acetonitrile. The related substances were successfully characterized through the accurate mass and elemental composition of the parent ions and their product ions determined by electrospray positive ionization high-resolution Q-Orbitrap/MS methods. Under the established analytical condition, apixaban and its related substances were well separated, and 30 related substances were detected and identified by hyphenated techniques in apixaban tablets and their stressed samples. Among them, 11 were known impurities and the rest 19 were unknown related substances identified for the first time in this study. The results obtained are valuable for apixaban manufacturing process optimization and quality control.

Objective To explore the normal reference range of perchlorate content in the urine of primary school students, and compare whether there are differences in their urine perchlorate contents among different populations, and to provide reference for the health care of primary school students. Methods A total of 441 primary school students aged 6 to 15 years old in a certain city were selected, and their urine samples were collected. The contents of perchlorate in the urine were determined by ultra-high performance liquid chromatography coupled with mass spectrometry, and the measurement data was statistically analyzed using SPSS software. Results There was no significant gender difference in the content of perchlorate in the urine of primary school students, but there was an age difference. The normal reference range for the content of perchlorate in the urine of primary school students aged 6-9 years old was 0-99.09 μg/L, and the normal reference range for the content of perchlorate in the urine of primary school students aged 10-15 years old was 0-74.56 μg/L. Conclusion Through the measurement and analysis of a large number of samples, a normal reference range for the content of urinary perchlorate in primary school students have been recommended.

Objective:To investigate the correlation between blood lipid variability and recurrence of cerebrovascular events in patients with ischemic stroke.Methods:Patients with ischemic stroke admitted to Qingdao Municipal Hospital from June 1, 2020 to December 31, 2022 were prospectively enrolled and followed up for 30 months. The standard deviation (SD) and coefficient of variation (CV) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were calculated during follow-up, and the attainment rate of blood lipid before and after follow-up were compared. The recurrence of cerebrovascular events was monitored, including ischemic stroke, cerebral hemorrhage, and transient ischemic attack. Cox proportional hazards regression model was used to analyze the correlation between the variability of TC, LDL-C, HDL-C, and TG and the recurrence of cerebrovascular events.Results:A total of 142 patients with ischemic stroke were enrolled, including 81 males (57.0%), aged 63.4±5.8 years. During follow-up, 34 patients (23.9%) experienced recurrent cerebrovascular events. At the end of the follow-up, TC, TG, and LDL-C levels decreased significantly compared to before the follow-up (all P<0.05), and the attainment rate of blood lipid increased significantly compared to before the follow-up (51.4% vs. 12.7%; P=0.001). CV of LDL-C in the recurrent group was significantly higher than that in the non-recurrent group ( P=0.005). Cox proportional hazards regression analysis showed that after adjusting for age, gender, body mass index, baseline blood lipids, and baseline blood pressure, LDL-C variability (SD: hazard risk [ HR] 4.051, 95% confidence interval [ CI] 2.671-5.687, P=0.034; CV: HR 3.785, 95% CI 2.356-5.013, P=0.041) and TC variability (SD: HR 3.821, 95% CI 2.450-5.224, P=0.039; CV: HR 3.715, 95% CI 2.401-5.036, P=0.042) during follow-up were independently associated with the recurrence of cerebral vascular events. Conclusions:LDL-C and TC variability are the independent influencing factors for the recurrence of cerebrovascular events in patients with ischemic stroke. Monitoring the variability of LDL-C and TC in patients with ischemic stroke and intervening in a timely manner may reduce the risk of recurrence of cerebrovascular events.

Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P＜0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P＜0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P＜0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P＜0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.

Objective To investigate the effect of varying ureteral wall thickness(UWT)at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy(URL).Methods The clinical data of 164 patients with ureteral stones in our hospital were retrospectively analyzed.According to different UWT,the patients were divided into the mild thickening group(84 cases,UWT<3.16 mm),the moderate thickening group(31 cases,UWT 3.16 to 3.49 mm),and the severe thickening group(49 cases,UWT>3.49 mm),and the differences of clinical related indicators among the three groups were compared.Results The incidence of postoperative renal colic and leukocyte disorder in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,and the differences were statistically significant(P<0.05).The postoperative catheterization time in the mild thickening group and the moderate thickening group were shorter than that in the severe thickening group,and the incidences of secondary lithotripsy,residual stones and stone return to kidney in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,with statistically significant differences(P<0.05).The length of hospital stay and hospitalization cost in the mild thickening group and the moderate thickening group were shorter/less than those in the severe thickening group,with statistically significant differences(P<0.05).Conclusion With the increase of UWT(especially when UWT>3.49 mm),the incidence of postoperative complications and hospitalization cost of URL increase to varying degrees,and the surgical efficacy decreases.In clinical work,UWT measurement holds potential value in predicting the surgical efficacy and complications of URL.

Objective:To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia(ET).Methods:The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed.According to driver mutation type,patients were divided into JAK2 group,CALR group and triple-negative group.The sex,age,cardiovascular risk factors,thrombosis,splenomegaly,routine blood test and coagulation status of patients in three groups were analyzed.Results:Among 69 ET patients,46 cases were associated with JAK2 mutation,14 cases with CALR mutation,8 cases with triple-negative mutation,and one with MPL gene mutation.There were no significant differences in age and sex among the three groups(P＞0.05).The highest thrombotic rate was 26.09％(12/46)in JAK2 group,then 12.5％(1/8)in triple-negative group,while no thrombotic events occurred in CALR group.The incidence of splenomegaly was the highest in JAK2 group(34.78％),while no splenomegaly occurred in triple-negative group.The white blood cell(WBC)count in JAK2 group was(9.00±4.86)× 109/L,which was significantly higher than(6.03±2.32)× 109/L in CALR group(P＜0.05).The hemoglobin(Hb)and hematocrit(HCT)in JAK2 group were(148.42±18.79)g/L and(0.44±0.06)％,respectively,which were both significantly higher than(131.00±15.17)g/L and(0.39±0.05)％in triple-negative group(P＜0.05).The platelet(PLT)in JAK2 group was(584.17±175.77)× 109/L,which was significantly lower than(703.07±225.60)× 109/L in CALR group(P＜0.05).The fibrinogen(Fg)in JAK2 and triple-negative group were(2.64±0.69)g/L and(3.05±0.77)g/L,respectively,which were both significantly higher than(2.24±0.47)g/L in CALR group(P＜0.05,P＜0.01).The activated partial thromboplastin time(APTT)in triple-negative group was(28.61±1.99)s,which was significantly decreased compared with(31.45±3.35)s in CALR group(P＜0.05).Conclusions:There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations.Among ET patients,JAK2 mutation is most common.Compared with CALR group,the thrombotic rate,WBC and Fg significantly increase in JAK2 group,while PLT decrease.Compared with triple-negative group,the incidence of splenomegaly and HCT significantly increase.Compared with CALR group,Fg significantly increases but APTT decreases in triple-negative group.

Objective:To compare the efficacy and clinical value of high-throughput sequencing(HTS)and Sanger sequencing in detecting ABL kinase domain mutations in patients with chronic myeloid leukemia(CML).Methods:A total of 198 samples of 147 CML patients from July 2017 to March 2021 in Henan Cancer Hospital were collected and underwent high-throughput sequencing and Sanger sequencing to detect the mutations in ABL kinase domain,and the relevant clinical data were collected for comparative analysis.Results:The proportion of total mutations and ≥ 2 mutations detected by high-throughput sequencing were significantly higher than those detected by Sanger sequencing(P=0.01;P=0.046).≥ 2 mutations were detected in 22 cases,of which 5 cases(22.7％)had compound mutations.High-throughput sequencing can detect low level mutations that cannot be detected by Sanger sequencing.In 198 samples,25(12.6％)were low level mutations,33(16.7％)were high level mutations and 10(5.1％)were mixed high and low level mutations.In the analysis of related clinical factors,the total mutation rate and the low level mutation rate in the optimal period,failure period and warning period were gradually increased(total mutation rate,P=0.016;low level mutation rate,P=0.005).The mutation rate of the samples with additional chromosomal abnormalities was also significantly increased(P=0.009).The mutation rate of patients who received first-and second-line treatment was significantly lower than that of patients who received third-or higher-line treatment(P=0.006).Analysis based on variant allele frequency(VAF)of the mutation site was helpful to visually evaluate the clonal evolution status of TKI-resistance CML cells.Conclusion:High-throughput sequencing is more sensitive and accurate than Sanger sequencing in mutation detection,which is helpful to accurately and visually evaluate TKI treatment response and optimize treatment strategy for CML.

Objective:To explore with healthy adults any effect on postural control of transcranial direct current stimulation (tDCS) applied over the left dorsolateral prefrontal cortex (L-DLPFC) and the primary motor cortex (M1).Methods:Eighteen healthy adults received 3 tDCS stimulation protocols sequentially applied to either the left dorsolateral prefrontal cortex alone, the left dorsolateral prefrontal cortex and the bilateral primary motor cortex simultaneously or sham stimulation, respectively. Each intervention protocol lasted for 20 minutes with a total current intensity of less than 4mA, with a 7-day interval between the each stimulation protocol. Single-task and dual-task walking and balance tests were administered before and after each stimulation protocol, followed by statistical analysis.Results:The results of the single-task gait function testing showed that the change in step width before and after single-target tDCS stimulation was (-0.511±1.072)cm, significantly better than with sham stimulation. In the dual-task gait function tests the change in step width after single-target tDCS stimulation was (-0.511±1.072)cm, significantly better than in the other two groups.Conclusions:Stimulating only the dorsolateral prefrontal cortex can effectively regulate cognitive-motor postural control. Multi-target tDCS offers no particular advantage.

Objective:To investigate the current status of pertussis laboratory diagnosis and confirmed pertussis cases reporting in Shaanxi Province, and evaluate the quality of case reports.Methods:The information of confirmed pertussis cases reported in Shaanxi Province from January to July 2022 was collected through the China Disease Control and Prevention Information System. The laboratory diagnostic methods and pertussis vaccine immunization history of confirmed cases were investigated, and the descriptive epidemiological method was used for statistical description.Results:Of the 164 confirmed cases of pertussis reported from January to July 2022, two were not tested in the laboratory and 162 were tested in the laboratory. The proportions of different detection methods were 1.85% (3/162) of isolation and culture, 31.48% (51/162) of serum antibody IgG, 14.20% (23/162) of serum antibody IgM, 49.38% (80/162) of serum antibody PCR and 3.09% (5/162) of serum antibody IgM+ PCR. Among the 79 serological positive cases, 12 cases (15.19%)had no history of pertussis immunization, and 15 cases (18.99%), 11 cases (13.92%) and 41 cases (51.90%) had the time interval from vaccination to detection of <1 year, 1-3 years and >3 years, respectively. Based on the analysis of laboratory testing methods and vaccination history, 38 cases were misdiagnosed/misreported among 164 cases, with a misdiagnosis or misreported rate of 23.17%. There were 17, 12 and 9 cases of misdiagnosis/misreport in 0-2 years old group, 3-6 years old group and≥7 years old group, and the misdiagnosis or misreported rates were 27.42%(17/62), 26.67%(12/45) and 15.79%(9/57), respectively.Conclusions:The selection of pertussis laboratory testing methods in some medical institutions in Shaanxi Province is incorrect, which leads to a certain proportion of misdiagnosis or misreport, and it is necessary to further strengthen the training and standardization.