Objective:To investigate the molecular etiology of Perrault syndrome by analyzing the clinical phenotype and pathogenic gene variants of 2 male patients with bilateral severe sensorineural deafness.Methods:Two male patients with Perrault syndrome characterized by severe sensonrineual deafness adimitted to the First Affiliated Hospital of Zhengzhou University between February 2021 and March 2022 were selected, and the clinical phenotype and pathogenic gene variants of them and their family members were summarized. The whole exome sequencing technology was used to screen the pathogenic variants of the probands, and the candidate variants were determined by combining with clinical phenotype. The probands and their family members were verified by the Sanger sequencing method.Results:The whole exome sequencing results showed that the proband of family 1 had a compound heterozygous variants of the LARS2 (NM_015340.4) gene c.1565C>A (p.Thr522Asn) and c.1079T>C (p.Ile360Thr). The reported pathogenic variant c.1565C>A came from the mother, and the novel variant c.1079T>C came from the father. The second proband harbored compound heterozygous variants of HARS2 gene (NM_012208.4) c.1273C>T (p.Arg425Trp) and c.1403G>C (p.Gly468Ala), with the former from the proband′s mother, the latter from the father. The c.1273C>T was novel and c.1403G>C was the reported pathogenic variant. All above variants were respectively classified as pathogenic, uncertain significance, uncertain significance and likely pathogenic based on the ACMG guidelines. Conclusion:This study expands the mutational spectrum of LARS2 and HARS2 genes, which highlights that genetic testing plays an important role in the early diagnosis of syndromic deafness.

Acute pancreatitis is a clinically common acute abdominal disease with complex etiology. Acute pancreatitis is reportedly related to the history of biliary tract disease, drinking, hyperlipidemia, age, body mass index, and other related risk factors. In terms of the severity of acute pancreatitis, there are different scoring indicators, laboratory testing indicators, and imaging evaluation indicators. The paper reviews the risk factors and severity evaluation of acute pancreatitis to standardize the treatment of patients, strengthen clinical nursing, and improve prognosis.

Objective:To screen the causative genes of five families with branchio-oto-renal syndrome (BORS) or branchio-oto syndrome(BOS) and to analyze the phenotypic characteristics and clinical management strategies of patients.Methods:Five families with BORS/BOR from December 2018 to September 2021 were recruited, information of patients, including family history and medical history, was collected, and genealogies were drawn. The examinations concerning audiology, nephrology, and radiology were performed on the affected individuals. Peripheral blood was obtained for DNA extraction, then next-generation sequencing technology was used to screen candidate variants associated with BORS/BOS. Based on patient′s clinical results, the appropriate interventions were recommended and implemented.Results:Eight individuals were diagnosed with BOS or BORS. Of the eight patients, all had hearing loss, preauricular pits and ear malformations, and only four presented with branchial cleft fistulae or cysts. Except for two patients(5-I-2, 5-II-2) who did not undergo renal examination, the remaining six lacked renal abnormalities. Genetic analysis identified four likely pathogenic or pathogenic EYA1 variants (c.1715G>T, c.1140+1G>A, c.639G>C, c.1475+1G>C; NM_000503.6), and c.1715G>T was first reported in this study. Middle ear ossicular reconstruction was performed in 1-II-2,2-I-2 and 3-II-2, but did not yield the expected results; then hearing aids and cochlear implantation were recommended and achieved satisfactory results. Conclusions:Next-generation sequencing technology facilitates the diagnosis and genetic counseling of BORS/BOS. Hearing loss, preauricular pits, ear malformations and branchial cleft fistulae or cysts are the most common manifestations of patients in this study. Middle ear surgeries for improving hearing loss may have some limitations in BORS/BOS patients, and hearing aids and cochlear implantation can contribute to hearing gains.

Objective:To evaluate the clinical efficacy of the bridge pedicled transplantation of medial leg fascial flap combined with medial hemisoleus muscle flap for contralateral leg soft tissue defect.Methods:Between January of 2012 and January of 2018, 12 patients with soft tissue defect of the leg were treated with bridge pedicled transplantation of contralateral medial leg fascial flap combined with medial hemisoleus muscle flap by posterior tibial artery. There were 9 males and 3 female, aged from 19 to 53 years (mean, 35 years). The size of the soft-tissue defects ranged from 12 cm×8 cm to 18 cm×9 cm. The immediate coverage of the fascial and muscle flaps and vessel pedicle were repaired by a meshed split-thickness skin graft. The donor site was closed directly. After the transplantation of the one pedicle and two flaps survived, vascular pedicle was cut off.Results:All the fascial and muscle flaps survived completely. No clinical vascular deficiency was found on the fascial and muscle flaps postoperatively. One case developed distal muscle flap small skin graft necrosis, and spontaneous healed after 2 weeks of dressing change. Follow-up period ranged from 2.5 to 4.5 years (mean 3.8 years). A good contour was confirmed both at the recipient and donor sites. Satisfactory clinical results were obtained in this series.Conclusion:This method is suitable for the treatment of soft tissue defects of the leg with only one major blood vessel, which reduces the damage to the donor site.

Objective:To evaluate the efficacy of the repairing anterior tibial adjacent double wounds by transposition with single-pedicle two flaps of the medial head of gastrocnemius.Methods:Between January of 2012 and January of 2018, 10 patients with the anterior tibial adjacent double wounds (7 males and 3 female, aged from 21 to 45 years) were treated by transposition with single-pedicle two flaps of the medial head of gastrocnemius. The size of the soft-tissue defects ranged from 2.0 cm×2.5 cm to 4.5 cm×4.0 cm. The medial head of the gastrocnemius was divided into two flaps with a single pedicle to repair two adjacent wounds of the anterior tibial. The muscle flaps were immediately covered by a meshed split-thickness skin graft, and the wound in donor site was closed directly.Results:All the muscle flaps survived completely. No clinical vascular deficiency was found on the muscle flaps postoperatively. Small wound dehiscence was developed in one patient and spontaneously healed 2 weeks after dressing change. Patients were followed up for 2.0 to 4.5 years. A good contour was confirmed at the recipient and donor sites. Satisfactory clinical results were obtained in this series.Conclusion:This method is suitable for the repair of two adjacent small wounds of the anterior tibial which can reduce the damage to the donor site.

Due to its advantages of low wear, high stability and flexibility, the new generation metal-on-metal hip prosthesis is favored by many patients with hip diseases, especially young patients. However, in recent years, several studies have indicated that adverse reactions to metal debris (ARMD) caused the formation of inflammatory pseudotumor, which ultimately led to a higher revision rate after metal-on-metal hip arthroplasty. This aroused the widespread concern from doctors and patients. Moreover, revision surgery for metal-on-metal hip arthroplasty in the setting of inflammatory pseudotumor is faced with a great risk of failure because of the large defects of bone and surrounding soft tissue and difficulty in removing the original prosthesis and the fixing of the modified prosthesis. Therefore, the use of such products is restricted with caution in their choice. We summarized the recent developments in the research in the risk factors, diagnosis and treatment of inflammatory pseudotumor after metal-on-metal hip arthroplasty. The risk factors for the formation of inflammatory pseudotumor around the hip prosthesis mainly include the increase of metal ion concentration, the position of prosthesis implantation and the patient's own factors. The diagnosis mainly depends on physical examination, imaging examination, laboratory examination, arthroscopy and histological examination. The treatment strategies for clinical symptomatic and asymptomatic patients are also varies. Through the detailed analysis, evaluation and summary of the above contents, we may provide guidance for the selection of hip prosthesis, and lay the foundation for further exploration of the mechanism of inflammatory pseudotumor caused by ARMD.

CD70/CD27 pathway plays an important role in human immune regulation.The role of CD70/CD27 pathway in immune regulation is mainly to promote the activation and proliferation of T cells,induce the differentiation and formation of effector T cells and memory T cells,and interfere with regulatory T cells.In addition,the high level of CD70 expression in some tumor cells provides a new way for tumor immunotherapy.

Objective: Investigate the effects of inducible ppp2r1a knockout on main physiological function in adult mice and study the mechanism. Methods: Ppp2r1a^flox/flox mice and CAGG-CreER mice were hybridized to obtain 20 CAGG-CreER ppp2r1a^flox/flox and 20 mice in homozygous group. Two groups of mice were divided into 4 groups respectively, finally we got 8 groups with 5 mice in each group. Tamoxifen was injected intraperitoneally to acquire inducible ppp2r1a knockout mice. The knockout efficiency of PP2A Aα in vital organs was measured by Western blot. At 0, 2, 4 and 6 days after injection, we measured body weight, histopathological change, peripheral blood cell counts and blood biochemical. Real-time PCR was performed to measure expression of liver glucolipid metabolism genes. Results: After tamoxifen injection for 6 days, the knockout efficiency of PP2A Aα in vital organs was 35%, 12%, 15%, 60%, 69% and 72%, respectively in heart, liver, spleen, lung, kidney and brain. After tamoxifen injection for 6 days, the weight of homozygous mice was lower than that of wild type mice, with values of (17.42±1.76) g and (21.69±1.82) g, respectively (P<0.05). Moreover, the activity level, abdominal and renal fat were significantly decreased in homozygous mice. Homozygous mice survived no more than 7 days. Compared with wild type mice, the organ coefficient of spleen of homozygous mice was decreased at the 6th day, with values of (0.59±0.10)% and (0.36±0.05)% respectively (P<0.05). Obvious spleen atrophy and marked decrease of nucleated cells were showed by performing HE staining. Tunel staining revealed increased apoptosis ratio of splenic lymphocytes in homozygous mice. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) of homozygous mice were higher than wild type mice (P<0.05). The values of ALT and AST in homozygous mice were (153.68±62.80) U/L and (193.2±44.28) U/L. The corresponding values in wild type mice were (41.02±12.91) U/L and (69.40±9.55) U/L. The above results indicated that ppp2r1a knockout caused liver damage. Blood sugar level of homozygous mice was lower than in wild type mice (P<0.05), with values of (4.20±1.99) mmol/L and (8.88±0.65) mmol/L respectively. Plasma total cholesterol (TC), high density lipoprotein (HDL) and β-hydroxybutyric acid (β-HB) level of homozygous mice were higher than those of wild type mice (P<0.05). The values of TC, HDL and β-HB in homozygous mice were (3.12±0.39), (1.53±0.38) and (2.49±0.89) mmol/L. The corresponding values in wild type mice were (1.69±0.92), (0.78±0.50) and (0.45±0.30) mmol/L respectively. The above results indicated that ppp2r1a loss interfered glucose and cholesterol metabolism. In addition, we also found that the white blood cell count (WBC) and lymphocyte count (LYM) of homozygous mice were lower than in wild type mice (P<0.05). The values of WBC and LYM in homozygous mice were (1.88±0.89)×10⁹/L and (0.92±0.37)×10⁹/L respectively. The corresponding values in wild type mice were (3.91±0.80)×10⁹/L and (2.74±0.52)×10⁹/L respectively. The mRNA levels of glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) of homozygous were lower than wild type mice (P<0.05). The fold change of G6P and PEPCK in homozygous mice was 0.46±0.11 and 0.72±0.07 respectively. The corresponding fold change in wild type mice was 1.02±0.07 and 1.02±0.06 respectively. Conclusion Whole body ppp2r1a is essential for the survival of adult mice, due to the important role in maintaining the metabolism of glucose and cholesterol of liver.

Objective To understand genetic distribution, drug resistance, molecular typing and the epidemiological relativeness between strains of the Shigella boydii virulence. Methods Nine Shigella boydii strains were isolated form stool samples of patients with diarrhea from the Enteric Disease Clinic of the Second Hospital of Tianjin Medical University in June-October 2015. The strains were identified by biochemical test and serum agglutination test. Antibiotics susceptibility test was carried out using the Kirby-Bauer method. Polymerase chain reaction was used for detecting virulence genes. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) technique were used to determine the epidemiological relationship between nine Shigella boydii strains. Results There were three subtypes in nine isolated Shigella boydii samples, including one, three and five isolates inⅠ,Ⅱ,Ⅳsubtypes respectively. All of the 9 isolates were multi-drug resistant. The resistant rate of these strains for ampicillin was 100%(9/9), and then the resistant rates of these strains for ceftazidime, streptomycin, gentamicin, trimethoprim/sulfamethoxazole, cefotaxime, ceftriaxone, norfloxacin and levofloxacin were 1/9, 4/9, 4/9, 4/9, 5/9, 5/9, 6/9, 6/9 and 6/9, respectively. All of these strains were sensitive to amikacin, cefperazone-sulbactam and imipenem. The ipaH was carried by all the testing strains, and none of the strains carried the sen, set1A, set1B, ial, virA, icsA and SigA. The detective rates of pic, sepA and sat were 4/9, 5/9 and 7/9 strains, respectively. Nine shigella boydii strains were divided into 8 PFGE types. The similarity between the spectrums of PFGE was 63.21%-100%. Multilocus sequence typing showed that six isolates were belonged to ST648, two isolates were ST131 and one isolate was ST10. Conclusion Nine isolates of Shigella boydii (divided into three subtyping) isolated from our hospital are multi-drug resistant and they have distant relationships, belonging to the dissemination of case.

Objective To investigate the clinical efficacy of fixation of distal radius fracture with dorsal instability with locking compression plate (LCP) via radial approach.Methods From September 2009 to October 2012, 21 cases underwent LCP fixation of the distal radius fracture with dorsal instability via radial approach.The study included 14 males and 7 females (mean age, 54.5 years;range, 38-81 years).Twelve cases were injured in traffic accidents, 7 in falls and 2 in high falls.Fracture AO classification was type A3 in 10 cases, type C1 in 8 cases and type C2 in 3 cases.Two cases (one type A3 and one type C1) had malunion.When the lateral column, intermediate column, radial edge and dorsal plane were exposed by radial incision, LCP fixation with bone grafting was performed to restore the height of radial styloid process, ulnar deviation and palmar tilt.According to the GartlandWerley score, wrist joint function was evaluated.Results Mean duration of follow-up was 13.5 months (range, 12 to 24 months).Stage Ⅰ bone union was shown on X-rays, with the healing time of 7.5 weeks.Based on the X-rays at postoperative 6 months, 1 year and 2 years, the shortening of radial styloid process was ≤ 2 mm, mean volar tilt was 12.5°(range, 8°-17°) , mean ulnar tilt was 20.5° (range, 15°-26°), and step-off or gap of the articular surface was ≤ 2 mm.In postoperative wrist motion assay, mean volar flexion was 60°(range, 30°-70°), mean dorsal flexion was 55° (range, 30°-65°), mean radial deviation was 17°(range, 10°-20°), mean ulnar deviation was 25.5° (range, 20°-30°),pronation was 65.5° (range, 60°-70°) , and mean supination was 75.5° (range, 60°-80°).Mean grip strength was 75％ (60％-95％)of the contralateral side.Two cases suffered from pain (one complained of moderate pain and one minor pain occasionally).According to the Gartland-Werley score, 16 cases were rated excellent, 2 good, 2 fair and 1 poor, with the excellent rate of 86％.No complication was found as injury of the superficial branch of radial nerve, infection, nonunion, nail loosening, medium neuritis and tendon injury.Conclusions Lateral column, intermediate column, radial edge and dorsal plane can be shown via the radial approach.LCP fixation combined with bone grafting contributes to fracture anatomical reduction.