Myelodysplastic syndrome (MDS) is a malignant hematologic tumor, which is currently difficult to cure. The theory of Xuanfu was proposed by Liu Wansu, which is unique in the clinical evidence of Chinese medicine and is less frequently applied to hematological diseases. The application of Xuanfu theory in myelodysplastic syndrome provides new ideas for the treatment of the disease. The abnormal flow of Qi, blood and fluids caused by the occlusion of the Xuanfu is the cause of toxic stasis obstruction, which is the pathogenesis of toxic stasis obstruction. Thus, the method of dispersion of Bone from Xuanfu, the external treatment of Xuanfu, and regulation of liver qi and Xuanfu help to return to normal of opening and closing function of Xuanfu, and release toxic stasis. In this paper, we analyzed the evidence of toxin-stasis obstruction in myelodysplastic syndrome from the theory of Xuanfu, aiming to provide a feasible theoretical basis for clinical treatment of the disease.

Objective:To investigate the etiological distribution of hydronephrosis caused by upper uri-nary tract obstruction in adult patients and to improve the diagnostic accuracy for this condition.Me-thods:The clinical information of adult patients with newly diagnosed hydronephrosis in Upper Urinary Tract Repair Outpatient Clinic of Peking University First Hospital from May 2020 to May 2021 were pro-spectively and continuously collected.Patients with ureteral calculi or upper urinary tract tumor were ex-cluded.A total of 767 patients were involved.The underlying causes of upper urinary tract obstruction were identified by senior urological surgeons according to symptoms,medical history,physical examina-tion,and a range of diagnostic imaging techniques including ultrasound,computed tomography(CT),magnetic resonance imaging(MRI),retrograde pyelography,antegrade pyelography,radionuclide reno-gram and ureteroscopy.Results:Among the 767 patients,359(46.8％)were male and 408(53.2％)were female.The median age of these patients was 37 years(range,14-84 years).Hydronephrosis was observed at left-sided in 357 cases(46.6％),right-sided in 251 cases(32.7％),and bilateral in 159 cases(20.7％).The causes of hydronephrosis were classified as follows:(1)Non-iatrogenic factors were found in 464 cases(60.5％).These included urinary malformations in 355 cases(76.5％),infec-tion in 29 cases(6.3％),pelvic lipomatosis and/or cystitis glandularis in 23 cases(5.0％),ureteral en-dometriosis in 18 cases(3.9％),retroperitoneal fibrosis in 15 cases(3.2％),trauma in 7 cases(1.5％)and other non-iatrogenic factors in 12 cases(2.6％).Some of these patients had multiple non-iatrogenic causes.Among the 355 cases with urinary system malformations,252 cases(71.0％)had ureteropelvic junction obstruction.(2)Iatrogenic ureteral injuries accounted for 210 cases(27.4％),including 112 cases(53.3％)of urological surgical injuries,51 cases(24.3％)of radiotherapy for malignant tumor re-lated injuries,34 cases(16.2％)of gynecological and obstetrical surgical injuries,and 13 cases(6.2％)of general surgical injuries.(3)The cause of hydronephrosis remained unknown in 93 cases(12.1％).Conclusion:Hydronephrosis in adults due to upper urinary tract obstruction has a diverse range of cau-ses,with urinary malformations and iatrogenic ureteral injuries being significant contributors.Urological surgeon involved in upper urinary tract reconstruction should be familiar with these potential causes to fa-cilitate accurate diagnosis and effective treatment.

Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Humans ; Blood Pressure/physiology* ; Cohort Studies ; Patient Discharge ; Ischemic Stroke ; Stroke ; Brain Ischemia ; Diabetes Mellitus ; Hypertension

BACKGROUND: Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps. METHODS: A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis. RESULTS: During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed. CONCLUSIONS ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.
Adult ; Humans ; Cardiovascular Diseases/prevention & control* ; East Asian People ; Prospective Studies ; Risk Factors ; Smoking

Objective:To investigate the effect of adenovirus-mediated short hairpin RNA (shRNA) downregulating SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) on the apoptosis of human hepatic stellate cells LX-2 cultured in vitro.Methods:The recombinant adenovirus Ad-shRNA/SHP2 carrying shRNA targeted SHP2 and expressing green fluorescent protein (GFP), and the empty control virus Ad-GFP expressing GFP were transfected into LX-2 cells cultured in vitro. Real-time fluorescence quantitative PCR was used to detect SHP2 mRNA expression in LX-2 cells. Western blot was used to detect the protein expressions of SHP2, Bax, and Bcl-2 in LX-2 cells. TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry were used to detect apoptosis in LX-2 cells. Experimental group: (1) Control group: LX-2 cells were transfected with DMEM instead of adenovirus; (2) Ad-GFP group: transfected with empty virus Ad-GFP; (3) Ad-shRNA/SHP2 group: transfected with recombinant adenovirus Ad-shRNA/SHP2. The means between multiple groups were compared using a one-way ANOVA and the LSD test was used for inter group comparisons.Results:shRNA-targeted SHP2 significantly down-regulated the expression of SHP2 protein and mRNA in LX-2 cells ( P < 0.05). The TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry results showed that the apoptosis rate of LX-2 cells in the Ad-shRNA/SHP2 group (12.755%±1.606%, 19.340%±2.505%) ( P < 0.05) was significantly higher compared to the control group (3.077%±0.731%, 9.438%±0.804%) and the Ad-GFP group (3.250%±0.851%, 8.893%±1.982%), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05). Western blot analysis of Bax and Bcl-2 protein expression in LX-2 cells of each group revealed that the Bax protein expression was significantly higher in the Ad shRNA/SHP2 group (2.493 ± 0.203) ( P < 0.05) compared to the control group and Ad-GFP group (1.989 ± 0.147, 1.999 ± 0.162), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05), while the Bcl-2 protein was significantly decreased in the Ad-shRNA/SHP2 group (1.042±0.148) compared with the control group and the Ad-GFP group (1.707±0.146, 1.521±0.142), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05). Conclusions:SHP2 expression down-regulation induces apoptosis of human hepatic stellate cells LX-2 in vitro by reducing Bcl-2/Bax.

Objective:To identify the pathogenic gene and inheritance pattern in a pedigree of congenital iris coloboma with congenital cataract.Methods:The method of pedigree investigation was adopted.A pedigree of congenital iris coloboma with congenital cataract was collected by Yunnan Disabled Rehabilitation Center and the 2nd Afliated Hospital of Kunming Medical University in February 2020.Ophthalmic examinations were carried out on the female proband, her parents, her children and her husband, and the clinical diagnosis was made.Genomic DNA was extracted from peripheral blood samples collected from the family members.The suspected pathogenic gene in the proband and her husband was screened by whole exome sequencing and was identified by bioinformatics analysis.The amino acid conservation was analyzed by UGENE software.The impact of the mutation on protein translation was predicted using MutationTaster software.The pathogenicity of the mutation was assessed according to the American College of Medical Genetics (ACMG) Standards and Guidelines.Pathogenic gene and mutations were verified by Sanger sequencing.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the 2nd Afliated Hospital of Kunming Medical University (No.PJ-2020-61).Written informed consent was obtained from each subject or custodian.Results:The proband showed large iris defects in both eyes with only a small amount of observable iris tissue in the periphery, lens cortical opacity and posterior capsule opacification, accompanied by nystagmus.A novel heterozygous frameshift variation c. 415dupA (p.R139fs) was located in exon 8 of PAX6 gene, and the variation was conservative across multiple species.The variation was in the highly conserved region of PAX6 gene and caused the dysfunction of PAX6 protein.The variation was graded as PVS1+ PM2+ PP1, a pathogenic variation, based on ACMG guidelines.The pedigree was consistent with co-segregation, indicating that the novel variation was pathogenic.The proband and her children were diagnosed, but her parents were phenotypically normal, in accordance with autosomal dominant inheritance. Conclusions:The novel frameshift variation c.415dupA (p.R139fs) on the exon 8 of PAX6 gene is responsible for congenital iris coloboma with congenital cataract in the pedigree.This is the first report of this novel variation in PAX6 gene.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Objective:To observe the clinical characteristics of patients with familial vitreous amyloidosis (FVA) and the efficacy of vitrectomy (PPV) and the occurrence of complications.Methods:A retrospective clinical study. From June 2009 to March 2020, 32 eyes of 18 patients from 3 FVA families who were diagnosed and treated by PPV at Department of Ophthalmology of Jiaxing TCM Hospital were included in the study. Among them, there were 12 males with 22 eyes and 6 females with 10 eyes. The average age of onset was 42.28±3.25 years; the average duration of disease was 3.75±3.93 years. All the affected eyes underwent best corrected visual acuity (BCVA) and B-mode ultrasound examination. A logarithmic visual acuity chart was used in the BCVA examination, which was converted to the logarithmic minimum angle of resolution (logMAR) visual acuity when recorded. The average logMAR BCVA of the affected eye was 1.72±0.53; the intraocular pressure was less than 21 mm Hg (1 mm Hg=0.133 kPa). The vitreous body of the affected eye was obviously cloudy. All the affected eyes underwent standard three-channel PPV through the flat part of the ciliary body, and vitreous specimens were collected for pathological examination during the operation. Peripheral venous blood of probands from 3 families was collected, and the whole exome gene sequencing was performed. The follow-up time after surgery was ≥6 months. The patient's clinical characteristics, fundus lesions in PPV, changes in BCVA after surgery, and complications was observed. One-way analysis of variance or t test was performed for measurement data comparison; χ2 test was performed for count data comparison. Results:The vitreous body of the affected eye showed gray-white dense and thick flocculent changes, and the posterior capsule attached to the lens showed "foot disc-like" turbidity; later the lens was mainly cystic opacity. Pathological examination of the vitreous body showed positive staining of Congo red; under a polarized light microscope, it showed apple green dots and sheet-like birefringence. The genetic test results showed that there was a c.307G>C (p.Gly103Arg) missense mutation in the TTR gene of the proband in Family 2. Peripheral retinal hemorrhages in 4 eyes (12.5%, 4/32), retinal tears in 5 eyes (15.6%, 5/32), retinal degeneration in 4 eyes (12.5%, 4/32), retinal detachment were found in PPV 3 eyes (9.4%, 3/32). The vitreous body was filled with C 3F 8 and silicone oil respectively for 2, 1 eye. Six months after the operation, the logMAR BCVA of the affected eye was 0.39±0.32, which was significantly higher than that before the operation, and the difference was statistically significant ( t=15.131, P=0.000). After the operation, high intraocular pressure occurred in 2 eyes (6.3%, 2/32), secondary glaucoma in 1 eye (3.1%, 1/32), retinal detachment in 2 eyes (6.3%, 2/32), neovascular glaucoma (NVG) in 2 eyes (6.3%, 2/32), cataract in 10 eyes (31.3%, 10/32). Conclusion:The vitreous body of FVA eyes are gray-white dense, thick and flocculent, attached to the posterior lens capsule, showing "foot disc-like" turbidity; PPV treatment can effectively improve the BCVA of the FVA eyes; secondary glaucoma, secondary retinal detachment, NVG can occur after surgery.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.