Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.

Objective To describe the distribution characteristics of knee and ankle joint range of motion and muscle atrophy related indexes in patients with Kashin-Beck disease(KBD)in Shaanxi Province so as to explore the correlation of knee and ankle joint range of motion(ROM)with muscle atrophy indexes and provide reference for clinical characteristics analysis of KBD patients.Methods To investigate the registered KBD patients from KBD areas in Shaanxi Province,we measured the general demographic data of the patients were collected and the ROM of the knee joint(flexion and extension),the ankle joint(dorsiflexion and plantar flexion),and the muscle atrophy related indexes such as the upper arm circumference,thigh circumference,calf circumference and grip strength.According to the population characteristics,i.e.,gender,age,body mass index(BMI)and KBD grade,the median and quartile of joint ROM and muscle atrophy of KBD patients were reported,and then the differences in each index among different groups were analyzed.Partial correlation analysis was used to explore the correlation between indicators after controlling for variables such as gender,age and BMI.Results A total of 480 patients with KBD were investigated in this study,who consisted of 249(51.9％)males and 231(48.1％)females,with an average age of(63.10±7.32)years and an average BMI of(23.49±8.90)kg/m2.The knee flexion ROM,knee extension ROM,ankle dorsiflexion ROM and ankle plantar flexion ROM were[105.0(95.0,120.0)]°,[0.0(-15.0,0.0)]°,[5.0(0.0,15.0)]° and[20.0(15.0,30.0)]°,respectively,in KBD patients in Shaanxi Province.The left thigh circumference,right thigh circumference,left calf circumference,right calf circumference,and upper arm circumference were[43.0(40.0,47.0)]cm,[43.0(39.0,47.0)]cm,[29.0(27.0,32.0)]cm,[29.5(27.0,32.0)]cm,[27.0(25.0,30.0)]cm,respectively.The left hand grip strength and right hand grip strength were[13.4(9.5,18.4)]kg and[13.9(9.8,18.2)]kg,respectively.With the increase of age,the extension range of the left and right knee joints of KBD patients showed a decreasing trend(H=31.499,31.847;all P＜0.001).The range of motion of bilateral knee flexion was higher in the normal BMI group than in the overweight or obese group,with statistically significant differences(H=7.753,12.333;P=0.021,0.002).The knee flexion,thigh circumference,and calf circumference of the left and right sides showed a decreasing trend under different KBD grades(H=14.345,17.256,8.000,8.462,8.558,9.633;all P＜0.05).Correlation analysis showed that knee flexion ROM was positively correlated with thigh circumference,calf circumference,and grip strength in patients with KBD(all P＜0.05).There was a positive correlation between knee extension ROM and thigh circumference in patients with KBD(P＜0.01).Conclusion The impaired joint ROM and muscle atrophy are serious in KBD patients in Shaanxi Province,and there is a correlation between joint motion and muscle atrophy.

Objective:To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy.Methods:A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results:Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG ( χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG ( χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion:Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.

Purpose: This study aims to explore whether neoadjuvant chemotherapy with immunotherapy (NACI) leads to different tumor shrinkage patterns, based on magnetic resonance imaging (MRI), compared to neoadjuvant chemotherapy (NAC) alone in patients with triple-negative breast cancer (TNBC). Additionally, the study investigates the relationship between tumor shrinkage patterns and treatment efficacy was investigated. Methods: This retrospective study included patients with TNBC patients receiving NAC or NACI from January 2019 until July 2021 at our center. Pre- and post-treatment MRI results were obtained for each patient, and tumor shrinkage patterns were classified into three categories as follows: 1) concentric shrinkage (CS); 2) diffuse decrease; and 3) no change.Tumor shrinkage patterns were compared between the NAC and NACI groups, and the relevance of the patterns to treatment efficacy was assessed. Results: Of the 99 patients, 65 received NAC and 34 received NACI. The CS pattern was observed in 53% and 20% of patients in the NAC and NACI groups, respectively. Diffuse decrease pattern was observed in 36% and 68% of patients in the NAC and NACI groups. The association between the treatment regimens (NAC and NACI) and tumor shrinkage patterns was statistically significant (p = 0.004). The postoperative pathological complete response (pCR) rate was 45% and 82% in the NAC and NACI groups (p < 0.001), respectively. In the NACI group, 17% of patients with the CS pattern and 56% of those with the diffuse decrease pattern achieved pCR (p = 0.903). All tumor shrinkage patterns were associated with achieved a high pCR rate in the NACI group. Conclusion Our study demonstrates that the diffuse decrease pattern of tumor shrinkage is more common following NACI than that following NAC. Furthermore, our findings suggest that all tumor shrinkage patterns are associated with a high pCR rate in patients with TNBC treated with NACI.

Objective     To investigate the effect and prognosis of patients with ventricular septal rupture after myocardial infarction treated by surgical repair combining an occluder and a patch. Methods     Clinical data of 42 patients with myocardial infarction complicated with ventricular septal rupture admitted to the First Affiliated Hospital of Zhengzhou University from January 2010 to September 2021 were retrospectively analyzed. According to the surgical methods, 27 patients were divided into a traditional group, including 17 males and 10 females, with an average age of 62.81±6.81 years, who were repaired by patch only, and 15 patients were divided into a modified group, including 11 males and 4 females, with an average age of 64.27±9.24 years, who were repaired by surgery combining an occluder and a patch. Perioperative and follow-up data of the two groups were compared and analyzed. Results     There were statistical differences between the two groups in preoperative Killip grading, rate of intra-aortic balloon pump use, interval from myocardial infarction to operation, and the number of culprit artery (P<0.05). There was no statistical difference in other preoperative data, the cardiopulmonary bypass time, aortic cross-clamping time, postoperative hospital stay or in-hospital death rate between the two groups (P>0.05). No residual shunt occurred in the modified group, and the difference was statistically significant compared with the traditional group (P=0.038). There was no statistical difference in other complications between the two groups (P>0.05). The median follow-up time was 4 years. Two patients in the traditional group and one in the modified group died during follow-up. The follow-up cardiac function grading of patients in the modified group was statistically different from that in the traditional group (P=0.023). Conclusion     The perioperative  mortality of ventricular septal rupture after myocardial infarction is high, but the long-term effect is satisfactory. Surgical repair combining an occluder and a patch is a safe and effective treatment for ventricular septal rupture, which can effectively reduce postoperative residual shunt.

Objective:To explore the technical points and efficacy of gradual traction-unlocking closed reduction technique (GT-UCRT) for Tile C old pelvic fractures.Methods:From August 2012 to June 2021, 6 patients with Tile C old pelvic fracture were treated and followed up at Department of Orthopedics, The Fourth Medical Center, General Hospital of Chinese PLA. They were 4 males and 2 females with an age of (35.8±10.5) years. By Tile classification: 4 cases of type C1.2, 1 case of type C1.3, and 1 case of type C2; time from injury to surgery: 153.8 (64.3, 204.8) days. The 6 patients were treated with GT-UCRT. The time for gradual traction reduction, operation time, hospital stay, intraoperative blood loss and complications were recorded. The modified Matta score was used to evaluate the reduction quality of pelvic fractures, and the Majeed score was used to evaluate the pelvic function at the last follow-up.Results:The 6 patients were followed up for (40.3±22.9) months (from 12 to 72 months) after surgery. The time for gradual traction reduction was (26.7±4.6) days, operation time (119.2±4.6) minutes, hospital stay (11.5±2.9) days, and intraoperative blood loss (533.3±189.6) mL. By the modified Matta score, the pelvic reduction after surgery was rated as satisfactory in 5 cases and as unsatisfactory in 1 case. The length disparity between both lower limbs in the 6 patients was (6.9±1.6) cm before surgery and (1.0±0.4) cm immediately after surgery, showing a statistically significant difference ( t=11.135, P<0.001). One fracture healed 3 months after surgery and 5 fractures 6 months after surgery. The Majeed pelvic score at the last follow-up was (80.8±9.0) points for the 6 patients, yielding 2 excellent cases, 3 good cases and 1 fair case. Delayed wound healing was reported in 1 patient, calf intermuscular venous thrombosis in 2 cases, and emotional anxiety and sleep disorder in 1 patient. No new lumbosacral plexus injury was found in any patient. Conclusions:In the treatment of Tile C old pelvic fractures, since our self-designed GT-UCRT combines the advantages of Ilizarov technique and unlocking closed reduction technique, it can not only protect the lumbosacral plexus but also obtain satisfactory reduction of the fracture.

Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K _d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease.

Objective:To evaluate the effect of acupuncture with invigorating viscera and purging fu, replenishing qi and nourishing yin for the T2DM patients with qi and yin deficiency syndrome.Methods:A total of 59 patients who met the inclusion criteria from January 1, 2019 to December 31, 2020 in the Endocrinology Department of the Second Affiliated Hospital of Anhui University of Chinese Medicine were divided into the acupuncture group with 30 cases and a control group with 29 cases, according to the random number table method. The control group received conventional hypoglycemic treatment. And the acupuncture group was treated with acupuncture on the basis of the control group treatment. Both groups were treated for 4 weeks. TCM syndrome scores were performed before and after treatment, respectively. Serum IL-6 was measured by ELISA, serum CRP by immunoturbidimetry, and serum fasting blood glucose (FPG), 2 hPG, HbAlc, TC, TG, HDL-C, LDL-C levels by spectrophotometry. The BMI, clinical effect rates were calculated.Results:The total effective rate was 96.7% (29/30) in acupuncture group and 75.9% (22/29) in control group, and the difference was statistically significant ( χ2=5.96, P<0.01). After treatment, the scores of fatigue, dryness of mouth and pharynx, spontaneous sweating and night sweating, shortness of breath and lazy speech in acupuncture group were significantly lower than those in the control group ( t values were 6.02, 4.31, 4.34, 3.63, respectively, all Ps<0.01). The serum CRP level in acupuncture group was significantly lower than that of the control group at 21, 48 d after treatment ( t values were -4.36, -3.75, respectively, all Ps<0.01), and IL-6 level was significantly lower than that of the control group at 14, 21, 28 d after treatment ( t values were -2.92, -5.35, -8.71, respectively, all Ps<0.01). After treatment, the serum TC [(4.62±0.68) mmol/L vs. (5.56±0.72) mmol/L, t=5.16], TG [(1.48±0.42) mmol/L vs. (2.12±0.89) mmol/L, t=3.55], LDL-C [(2.48±0.84) mmol/L vs.(3.02±0.95) mmol/L, t=2.32] in the acupuncture group were significantly lower than those in the control group ( P<0.05), HDL-C [(1.39±0.27) mmol/L vs. (1.26±0.22) mmol/L, t=-2.02] in the acupuncture group was significantly higher than that of the control group ( P<0.05). The serum FPG level at 21 d [(6.12±0.67) mmol/L vs. (6.57±0.61) mmol/L, t=-4.96], 28 d [(5.78±0.52) mmol/L vs. (6.49±0.58) mmol/L, t=-2.70] in acupuncture group were significantly lower than those in the control group ( P<0.01). The 2h PG level at 14 d after treatment [(10.23±1.06) mmol/L vs. (11.76±1.34) mmol/L, t=-4.87], 21 d [(9.05±0.98) mmol/L vs. (10.53±1.24) mmol/L, t=-5.10], 28 d [(7.45±0.69) mmol/L vs. (9.31±0.78) mmol/L, t=-9.71] in the acupuncture group were significantly lower than those in the control group ( P<0.01), and HbA1c level were decreased 14 d [(7.93±0.86)% vs. (8.52±0.97)%, t=-2.47], 21 d [(7.63±0.85)% vs. (8.15±0.92)%, t=-2.26], 28 d [(6.47±0.51)% vs. (7.51±0.62)%, t=-7.05] significantly lower than those in the control group ( P<0.01), BMI [(22.13±1.57) kg/m 2vs. (24.16±1.82) kg/m 2, t=-4.59] 28 d after treatment was significantly lower than that of the control group ( P<0.01). Conclusion:Acupuncture therapy of nourishing viscera and purging fu, nourishing qi and nourishing yin can regulate the disorder of glucose and lipid metabolism in patients with T2DM and syndrome of qi and yin deficiency.

OBJECTIVE: To detect the mutation site in a pedigree affected with autosomal dominant polycystic kidney disease (ADPKD) and verify its impact on the protein function. METHODS: Peripheral blood samples were collected from the proband and his pedigree members for the extraction of genomic DNA. Mutational analysis was performed on the proband through whole-exome sequencing. Suspected variant was verified by Sanger sequencing. A series of molecular methods including PCR amplification, restriction enzyme digestion, ligation and transformation were also used to construct wild-type and mutant eukaryotic expression vectors of the PKD2 gene, which were transfected into HEK293T and HeLa cells for the observation of protein expression and cell localization. RESULTS: The proband was found to harbor a c.2051dupA (p. Tyr684Ter) frame shift mutation of the PKD2 gene, which caused repeat of the 2051st nucleotide of its cDNA sequence and a truncated protein. Immunofluorescence experiment showed that the localization of the mutant protein within the cell was altered compared with the wild-type, which may be due to deletion of the C-terminus of the PKD2 gene. CONCLUSION The c.2051dupA (p. Tyr684Ter) mutation of the PKD2 gene probably underlay the pathogenesis of ADPKD in this pedigree.
DNA Mutational Analysis ; Female ; Frameshift Mutation ; HEK293 Cells ; HeLa Cells ; Humans ; Male ; Pedigree ; Polycystic Kidney, Autosomal Dominant/physiopathology* ; Protein Kinases/genetics* ; Protein Transport/genetics* ; Whole Exome Sequencing

OBJECTIVE: To analyze the pathogenic variant of preaxial polydactyly in a Chinese Han pedigree and identify the cause of polydactyly. METHODS: The peripheral blood DNA of the proband and her parents was extracted. The polydactyly-related genes were detected by trio whole exome sequencing, and the suspected pathogenic gene was screened out. Sanger sequencing was applied to other members of the pedigree. RESULTS: The results of gene sequencing showed that the LMBR1 gene had a heterozygous variant of c.423+4909(IVS5)C>T in 6 patients of the pedigree. The same variant was not detected in family members with normal phenotype. Based on the ACMG guidelines, c.423+4909(IVS5)C>T of the LMBR1 gene was predicted to be pathogenic (PM1+PM2+PP1-S(PS)+PP4+PP5). CONCLUSION The heterozygous C>T variant at position 4909 of intron 5 of the LMBR1 gene probably underlies the disease in this pedigree.
China ; Female ; Humans ; Mutation ; Pedigree ; Polydactyly/genetics* ; Thumb ; Whole Exome Sequencing