OBJECTIVE: To detect potential variants in a family affected with Usher syndrome type I, and analyze its genotype-phenotype correlation. METHODS: Clinical data of the family was collected. Potential variants in the proband were detected by high-throughput sequencing. Suspected variants were verified by Sanger sequencing. RESULTS: The proband developed night blindness at 10 year old, in addition with bilateral cataract and retinal degeneration. Hearing loss occurred along with increase of age. High-throughput sequencing and Sanger sequencing revealed that she has carried compound heterozygous variants of the MYO7A gene, namely c.2694+2T>G and c.6028G>A. Her sister carried the same variants with similar clinical phenotypes. Her daughter was heterozygous for the c.6028G>A variant but was phenotypically normal. CONCLUSION The clinical features and genetic variants were delineated in this family with Usher syndrome type I. The results have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.
Child ; Female ; Genetic Variation ; Genotype ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Myosin VIIa ; genetics ; Night Blindness ; etiology ; Pedigree ; Phenotype ; Usher Syndromes ; genetics ; pathology

Objective:To discuss the clinical effect about the external locking compression plate(LCP) combined with lower abdominal conjoined flap for fixing the open fracture and covering the soft tissue defects on tibia.Methods:From August 2017 to December 2020, 18 patients with serve tibial open fracture were admitted into the trauma center, including 15 males and 3 females with a median age of 38 (ranged, 25-58) years old. The etiology involving: 9 cases by traffic accident, 3 by downfall, 6 by crushing, which classified as type III B( n=6) and III C( n=12) by the Anderson-Gustilo criterion. All wounds were taken radical debridement, fixed by the femur LCP and covered by the VSD during the emergency operation. The lower abdominal conjoined flap was dissected to cover the soft tissue defect, of which the dimension and pedicle length were tailored to the defect. Primary closure was performed on the donor site. Followed-up was conducted by telephone and WeChat. Results:One flap was changed to gastrocnemius myocutaneous flap because of the venous crisis. Seventeen flaps survived completely without significant complications. All the donor and recipient sites had primary healing. A mean follow-up of 15 (ranged, 12 to 18) months. The fracture healed without bone infection and bone nonunion. The aesthetic outcomes were satisfied without overgrown hairy and hyperpigmentation for all flaps. The concealed linear scar was left without hernia or other morbidity on the donor site. At the final follow-up, 12 cases were excellent and 6 cases were good evaluated by the Johner-Wruhs criteria.Conclusion:The external LCP can immobilise the knee and ankle joint with the preservation of the soft tissue, and the free lower abdominal conjoined flap was useful for covering extreme defects with concealed donor site, with enough tissue volume. The combination of both could lower the postoperative infection, reduce the operation time and shorten the hospital stay.

Background and objective Small cell lung cancer(SCLC)is known as recalcitrant cancer with high malignancy and heterogeneity.Immunotherapy has changed the treatment pattern of extensive-disease SCLC(ED-SCLC),but the beneficiary population is limited.Therefore,exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC.SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase Ml(PKM1)is one of the isozymes of PK,an important rate-limiting enzyme in glycolysis pathway.Previous studies have shown that PKM1 is related to autophagy and drug sensitivity,however,how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear.The aim of this study was to investigate the biological functions of PKM1 in SCLC,including its effects on proliferation,migra-tion,autophagy,drug sensitivity,and expression of neuroendocrine(NE)-related markers in SCLC.Methods Western blot was used to detect the expression level of PKM1 in SCLC cells.PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection.Proliferation of cells and drug sensitivity were detected by MTT,and migration ability of cells was determined by Transwell.The level of autophagy was detected by flow cytometry.Western blot was used to determine the expression levels of NE-related proteins.Results PKM1 was differentially expressed among various SCLC cell lines,and was lower in H1092 cells(P＜0.01).Compared with the control group,there was no significant difference in proliferation level of PKM1 overexpressing H1092 cell,but the migration ability was significantly increased(P＜0.001),the drug sensitivity was re-duced,and the level of autophagy was inhibited(P＜0.001).Additionally,overexpression of PKM1 could upregulate the expres-sion of non-neuroendocrine(non-NE)-related proteins(P＜0.01)and decrease the expression of NE-related proteins(P＜0.01).Conclusion PKM1 was differentially expressed in SCLC cell lines,and high expression of PKM1 did not affect the prolifera-tion,but affected the migration of SCLC cells.PKM1 might affect drug sensitivity by inhibiting autophagy and regulating the expression of NE markers.These results provide a theoretical basis for exploring the role of PKM1 in SCLC.

Objective:To evaluate the effect of the free anterolateral thigh flap with nerve and the sural neurocutaneous flap on ankle and foot tissue defect, and to provide guidance for clinical selection.Methods:From May 2016 to May 2019, we reviewed and analyzed the data of patients with soft tissue injury of ankle and foot repaired by flap from Microsurgery Repair and Reconstruction Center, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University. According to the surgical method, they were divided into the free anterolateral thigh flap with nerve group and the sural neurocutaneous flap group. The survival rate of the 2 groups of skin flaps were calculated. According to the trial standard for evaluation of upper limb function in Chinese Medical Association Hand Surgery Society, the flaps were rated as excellent, good, and acceptable. And the excellent and good rates were counted. The incidence of regional complications of the 2 groups were counted. SPSS 26.0 software was used for analysis, the measurement data were subjected to t-test, expressed as mean±standard deviation; the categorical variables were subjected to chi-square test or Fisher’s exact probability method, and P<0.05 indicated that the difference was statistically significant. Results:A total of 59 patients with soft tissue defects in the foot and ankle were included. Among them, 21 cases were repaired with free anterolateral thigh flaps with nerve (group A), 12 males and 9 females, with an average age of 42.1 years, and the defect area was 4 cm×6 cm-11 cm ×16 cm, followed up for an average of 12.3 months after surgery; 17 cases of sural neurocutaneous flap repair (group B), 11 males and 6 females, average age 45.3 years, defect area 5 cm×5 cm-10 cm× 14 cm, the average follow-up was 11.3 months. There were no statistically significant differences in age, gender and cause of injury between the two groups ( P<0.05). The area of the flaps in group A and group B were (53.0±12.2) cm 2 and (46.4±9.62) cm 2, respectively. There was no significant difference between the two groups ( t=1.824, P=0.076). The flaps were all survived in both groups. Among them, 2 cases of group A had partial necrosis at the distal end of the flaps and healed after post-treatment; 1 case of group B had vascular crisis after operation, and the flaps survived after exploratory decompression. The first-stage survival rate of skin flaps in group A was 90.5% (19/21), and the first-stage survival rate of skin flaps in group B was 94.1% (16/17). The difference was not statistically significant ( P=1.000). According to the trial standard of upper limb function evaluation of the Chinese Medical Association Hand Surgery Society, the skin flaps in group A were excellent in 10 cases, good in 7 cases, and fair in 4 cases, with an excellent and good rate of 81.0% (17/21). In group B, skin flaps were excellent in 3 cases and good in 3 cases. Of the 11 cases, the excellent and good rate was 35.3% (6/17), and the difference was statistically significant ( P=0.007). The flap donor area in group A healed well without related complications. In group B, 2 patients (11.8%) developed scar contracture deformity after the flap donor area, which affected calf function, and the function recovered after the second-stage scar was released. The incidence of complications in the region was not statistically significant ( P=0.193). Conclusions:Both the free anterolateral thigh flap with nerve and the sural neurocutaneous flap can repair the soft tissue defect of foot and ankle with high survival rate. But the sural neurocutaneous flap has a higher good rate than the free anterolateral thigh flap with nerve, and the donor site is affected smaller.

Objective:To evaluate the effect of the free anterolateral thigh flap with nerve and the sural neurocutaneous flap on ankle and foot tissue defect, and to provide guidance for clinical selection.Methods:From May 2016 to May 2019, we reviewed and analyzed the data of patients with soft tissue injury of ankle and foot repaired by flap from Microsurgery Repair and Reconstruction Center, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University. According to the surgical method, they were divided into the free anterolateral thigh flap with nerve group and the sural neurocutaneous flap group. The survival rate of the 2 groups of skin flaps were calculated. According to the trial standard for evaluation of upper limb function in Chinese Medical Association Hand Surgery Society, the flaps were rated as excellent, good, and acceptable. And the excellent and good rates were counted. The incidence of regional complications of the 2 groups were counted. SPSS 26.0 software was used for analysis, the measurement data were subjected to t-test, expressed as mean±standard deviation; the categorical variables were subjected to chi-square test or Fisher’s exact probability method, and P<0.05 indicated that the difference was statistically significant. Results:A total of 59 patients with soft tissue defects in the foot and ankle were included. Among them, 21 cases were repaired with free anterolateral thigh flaps with nerve (group A), 12 males and 9 females, with an average age of 42.1 years, and the defect area was 4 cm×6 cm-11 cm ×16 cm, followed up for an average of 12.3 months after surgery; 17 cases of sural neurocutaneous flap repair (group B), 11 males and 6 females, average age 45.3 years, defect area 5 cm×5 cm-10 cm× 14 cm, the average follow-up was 11.3 months. There were no statistically significant differences in age, gender and cause of injury between the two groups ( P<0.05). The area of the flaps in group A and group B were (53.0±12.2) cm 2 and (46.4±9.62) cm 2, respectively. There was no significant difference between the two groups ( t=1.824, P=0.076). The flaps were all survived in both groups. Among them, 2 cases of group A had partial necrosis at the distal end of the flaps and healed after post-treatment; 1 case of group B had vascular crisis after operation, and the flaps survived after exploratory decompression. The first-stage survival rate of skin flaps in group A was 90.5% (19/21), and the first-stage survival rate of skin flaps in group B was 94.1% (16/17). The difference was not statistically significant ( P=1.000). According to the trial standard of upper limb function evaluation of the Chinese Medical Association Hand Surgery Society, the skin flaps in group A were excellent in 10 cases, good in 7 cases, and fair in 4 cases, with an excellent and good rate of 81.0% (17/21). In group B, skin flaps were excellent in 3 cases and good in 3 cases. Of the 11 cases, the excellent and good rate was 35.3% (6/17), and the difference was statistically significant ( P=0.007). The flap donor area in group A healed well without related complications. In group B, 2 patients (11.8%) developed scar contracture deformity after the flap donor area, which affected calf function, and the function recovered after the second-stage scar was released. The incidence of complications in the region was not statistically significant ( P=0.193). Conclusions:Both the free anterolateral thigh flap with nerve and the sural neurocutaneous flap can repair the soft tissue defect of foot and ankle with high survival rate. But the sural neurocutaneous flap has a higher good rate than the free anterolateral thigh flap with nerve, and the donor site is affected smaller.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.