Research progress of pathomics in head and neck neoplasms / 国际肿瘤学杂志

Pathomics, the integration of digital pathology and artificial intelligence, is used to assess tumor diagnosis, treatment and prognosis by extracting, screening and analyzing the data features contained in pathological pictures. In recent years, more and more pathomics studies of head and neck neoplasms have shown great value in the areas of computer-assisted diagnosis, tumor microenvironment and biomarker identification as well as prognosis evaluation. It is expected to play an important role in clinical assistance and precise treatment of head and neck neoplasms in the future.

Analysis of ARID1B gene variants in two Chinese pedigrees with Coffin-Siris syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for two Chinese pedigrees affected with Coffin-Siris syndrome (CSS).@*METHODS@#Whole exome sequencing (WES) was carried out for the probands. Candidate variants were verified by Sanger sequencing of the probands and their family members.@*RESULTS@#The two probands were respectively found to harbor a heterozygous c.5467delG (p.Gly1823fs) variant and a heterozygous c.5584delA (p.Lys1862fs) variant of the ARID1B gene, which were both of de novo in origin and unreported previously. Based on the guidelines of American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PS2+PM2).@*CONCLUSION@#The c.5467delG (p.Gly1823fs) and c.5545delA (p.Lys1849fs) variants of the ARID1B genes probably underlay the CSS in the two probands. Above results have enabled genetic counselling and prenatal diagnosis for the pedigrees.

Endoscopic cryoablation for upper tract urothelial carcinoma: pilot clinical experience / 中华泌尿外科杂志

Objective:To evaluate the safety and efficacy of endoscopic cryoablation (ECA) in patients with upper tract urothelial carcinoma (UTUC).Methods:The clinical data of 9 patients with UTUC treated with ECA from April 2018 to September 2019 were retrospectively analyzed. Patients consisted of 3 males and 6 females, with median age of 76 years old (ranging from 50 to 88 years old). Among the patients, 6 cases had tumors of ureter, 1 case had tumor of renal pelvis and 2 cases had tumors of renal pelvis combined with ureter. Of the 9 patients, two had bilateral UTUC, six were presented with single lesion, three were presented with multiple lesion. The size of tumors were (1.53±0.91)cm. The tumors of all cases were localized (≤stage T 2), and there was no carcinoma or suspicious lymph node/distant metastasis. All patients enrolled in this study had strong will to choose kidney-sparing therapy. Biopsy, resection of intraluminal lesion with laser and cryoablation under ureteroscopy or percutaneous nephroscopy was performed under general aneasthesia.Ureteroscopy was performed 3 months after cryoablation. Perioperative complications and follow-up results were recorded and assessed. Results:Cryoablation was successfully performed in patients under ureteroscopy (n=8) or nephroscopy (n=1). The median cryoablation time was 6 (ranging from 4-16) minutes. The median follow-up was 16 months (ranging from 4-24 months). No tumor recurrence was observed at primary sites during follow-up. Two patients with multiple lesions were observed denovo ureteral neoplasms outside the primary sites 3 months and 6 months after cryoablation and treated with second cryoablation. One case died due to cardiovascular events 4 months after surgery. One patient underwent ureteral stricture during follow-up and received ureteroscopic balloon dilatation. No recurrent stricture was found in this case during the subsequent follow-up of 16 months. The other 5 cases showed no recurrence or complications like stricture during follow-up.Conclusions:ECA could probably be a promising treatment for localized UTUC. No recurrence in primary site and low incidence of ureteral stricture was observed during follow-up. The efficacy and safety of ECA need to be verified with large sample study.

A buttress plate combined with Kirschner wires for Regan-Morrey type Ⅱ coronoid fracture in elbow terrible triad injury / 中华创伤骨科杂志

Objective:To evaluate the curative efficacy of a buttress plate combined with Kirschner wires for treatment of Regan-Morrey type Ⅱ coronoid fracture after elbow terrible triad injury.Methods:A retrospective study was conducted of the 20 patients who had been surgically treated for Regan-Morrey type Ⅱ coronoid fracture after elbow terrible triad injury from August 2014 to August 2018 at Department of Pelvic Trauma, Henan Luoyang Orthopedic-Traumatological Hospital. They were 12 men and 8 women, aged from 18 to 60 years (average, 39 years), with 6 left and 14 right sides affected. All the coronoid fractures were fixated with Kirschner wires plus a buttress plate through the anterior approach, the radial head and lateral collateral ligaments (LCL) were repaired through the posterolateral approach, and the medial collateral ligament (MCL) was repaired or fixated with a hinged external fixator if necessary. The curative efficacy was evaluated at the last follow-up by range of motion (ROM) of the elbow, Mayo elbow performance score (MEPS), American Shoulder and Elbow Surgeons Scale (ASES) and radiographs of the elbow. Complications were also recorded.Results:The mean follow-up time was 18 months (from 12 to 24 months) and the mean healing time 5 months. At the last follow-up, ROM in flexion and extension of the affected elbow joint averaged 132.5°, ROM in elbow pronation-supination 150°, MEPS 88, and ASES 87. No subluxation or dislocation occurred after elbow surgery. The fracture of coronoid process was slightly displaced in one case but eventually healed without affecting any elbow function; fat liquefaction occurred around the posterolateral incision in 2 cases but healed after debridement; traumatic arthritic changes occurred in 5 patients but no significant dysfunction of the elbow was observed.Conclusion:A buttress plate combined with Kirschner wires can lead to fine curative efficacy for Regan-Morrey type Ⅱ coronoid fracture after elbow terrible triad injury.

Anatomical locking plate versus common reconstruction plate in the treatment of acetabular posterior wall fracture / 中华创伤骨科杂志

Objective:To compare the curative effects between anatomic locking plate and common reconstruction plate in the treatment of acetabular posterior wall fracture.Methods:The 50 patients with acetabular posterior wall fracture were retrospectively analyzed who had been admitted to Department of Pelvic Trauma Surgery, Luoyang Orthopaedic Hospital of Henan Province from February 2015 to February 2020. They were assigned into 2 groups according to different internal fixation methods. In the reconstruction plate group of 24 patients whose fractures were fixated by a common reconstruction plate from February 2015 to June 2017, there were 21 males and 3 females with an age of (38.9±10.9) years. In the anatomical plate group of 26 patients whose fractures were fixated by an anatomic locking plate between July 2017 and February 2020, there were 20 males and 6 females with an age of (38.0±10.0) years. The 2 groups were compared in terms of operation time, intraoperative blood loss, reduction quality, hip function and complications at the last follow-up.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating the 2 groups were comparable ( P>0.05). The 50 patients were followed up for 18 to 26 months (mean, 22 months). The operation time [(132.8±8.6) min] and intraoperative blood loss [(357.0±14.7) mL] in the anatomic plate group were significantly less than those [(177.2±5.9) min and (492.0±17.6) mL] in the reconstruction plate group( P<0.05). Postoperative CT examination showed that 96.2% (25/26) of the patients in the anatomical plate group and 91.7% (22/24) of the patients in the reconstruction plate group had a fracture step ≤3 mm, showing no significant difference ( P>0.05). At the last follow-up, the excellent and good rate by Harris hip score was 92.3% (24/26) in the anatomic plate group, significantly higher than that (66.7%, 16/24) in the reconstruction plate group ( P<0.05). The incidence of complications was 3.8% (1/26) in the anatomic plate group, significantly lower than that [29.2% (7/24)] in the reconstruction plate group ( P<0.05). Conclusion:Anatomical locking plate is better than common reconstruction plate in the treatment of acetabular posterior wall fracture.

Minimally invasive three-window incision and novel anatomical locking plate for treatment of calcaneal fractures / 中华创伤骨科杂志

Objective:To investigate the efficacy of a minimally invasive three-window incision and internal fixation with a novel anatomical locking plate in the treatment of calcaneal fractures.Methods:A retrospective analysis was performed of the 46 patients with calcaneal fracture (Sanders typeⅡ and Ⅲ) who had been admitted to Department of Orthopedics, Luoyang Orthopaedic Hospital of Henan Province from February 2015 to May 2017. They were 22 males and 24 females, aged from 19 to 59 years (average, 39.0 years) and with 16 left and 30 right sides affected. They were all treated with a minimally invasive three-window incision and internal fixation with a novel anatomic locking plate. Their B?hler and Gissane angles, and height, width and length of the calcaneus were compared between preoperation, immediate postoperation and the last follow-up. Their ankle-hindfoot functions were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) scoring scale at the last follow-up; their complications were recorded.Results:All the 46 patients were followed up immediately after operation and for 14 to 18 months (mean, 16 months). All the fractures achieved bony union after an average of 3 months (from 2 to 4 months). At immediate postoperation and at the last follow-up, their calcaneal B?hler angles (34.20°±3.62° and 34.05°±3.65°) and Gissane angles (131.45°±6.04° and 131.25°±5.88°), and calcaneal heights [(41.05±2.76) mm and (40.90±2.86) mm], widths [(25.65±1.53) mm and (25.55±1.64) mm] and lengths [(76.82±1.70) mm and (76.73±1.78) mm] were significantly improved compared with the preoperative values [10.55°±7.51°, 95.32°±12.16°, (26.10±4.54) mm, (37.71±3.42) mm and (65.91±2.10) mm] ( P<0.05). There were no significant differences in the above indexes between immediate postoperation and the last follow-up ( P>0.05). According to AOFAS ankle-hindfoot scores at the last follow-up, the efficacy was evaluated as excellent in 28 cases, as good in 12 cases and as fair in 6 cases, yielding an excellent and good rate of 87.0%. No incision infection occurred after operation. Conclusion:In the treatment of calcaneal fractures of Sanders type Ⅱ and Ⅲ, the minimally invasive three-window incision and internal fixation with the novel calcaneal anatomical locking plate can achieve satisfactory reduction and rigid fixation, effectively reducing postoperative incision complications.

Mutation analysis and prenatal diagnosis for 50 pedigrees affected with Duchenne/Becker muscular dystrophy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To establish individualized prenatal diagnosis program for families affected with Duchenne/Becker muscular dystrophy (DMD/BMD) and different clinical background using a variety of methods.</p><p><b>METHODS</b>Multiplex ligation-dependent probe amplification (MLPA) was performed on 50 patients suspected for DMD/BMD. For single exon deletions of the DMD gene, PCR was used for validating the results. For those without any deletion or duplication, Sanger sequencing was used to screen for DMD gene mutations in the children and their mothers. Prenatal genetic testing was provided to female carriers using chorionic villus, amniocentesis or cord blood samples. To ensure the accuracy of diagnosis, all prenatal specimens were also subjected to linkage analysis.</p><p><b>RESULTS</b>Among the 50 patients with DMD/BMD, 23 harbored large deletions, 11 only had single exon deletions, 10 harbored duplications, and 5 had small scare mutations. No mutation was detected in one family. For 37 women undergoing prenatal diagnosis, 10 fetuses were identified as affected males, 6 were female carriers, while 21 were not found to carry any mutation. Testing of creatine kinase was consistent with the results of prenatal diagnosis. For a patient harboring exon 51 deletion, the same mutation was found in a fetus but not in their mother. The proband and fetus had inherited the same haplotype, which suggested that the mother probably has germline mosaicism for the mutation.</p><p><b>CONCLUSION</b>Application of individualized methods for analyzing pregnant women with different clinical background can minimize the risk for giving birth to further children affected with DMD/BMD.</p>

Survival analysis for high-grade glioma patients who received comprehensive treatment / 中南大学学报(医学版)

Objective:To analyze the curative effect and prognostic factors for comprehensive therapy in patients with high-grade glioma.Methods:Patients with high-grade glioma (WHO grade Ⅲ,grade Ⅳ) were chosen from July 2008 to May 2016 in the Hunan Cancer Hospital,and a retrospective analysis was performed in 64 patients with complete follow-up data.Results:The follow-up time was 3-111 (median 29.5) months,the median overall survival time was 36.00 (95％ CI 22.85 to 49.16) months,the median progression-free survival time (PFS) was 21.00 (95％ CI 9.72 to 32.28) months,The 1-year,2-year,3-year and 5-year survival rates of high-grade glioma patients were 87.50％,56.25％,40.63％ and 17.19％,respectively.The univariate analysis of Log-Rank test and the Cox regression model analysis showed that the prognostic factors related to the prognosis of high-grade glioma patients were pathological grade,resection degree,and concurrent chemo-radiotherapy (P＜0.05).Conclusion:The overall survival time,progression-free survival time and the 5-year survival rate of patients with high-grade glioma after comprehensive treatment is partially improved.The factors relevant to the prognosis of patients with high-grade glioma are pathological grade,resection degree,and concurrent chemo-radiotherapy,indicating that the glioma patients (WHO grade Ⅲ) received total resection of the tumor and concurrent chemo-radiotherapy have better clinical effect.

Carboxymethyl chitosan thermosensitive hydrogel induces the differentiation of bone marrow mesenchymal stem cells toward neurons / 中国组织工程研究

BACKGROUND:Chitosan biological materials can induce bone marrow mesenchymal stem cells to differentiate toward neurons. As a derivative of chitosan, carboxymethyl chitosan has a series of excelent properties. However, whether carboxymethyl chitosan can induce the neuronal differentiation of bone marrow mesenchymal stem cells remains unclear.OBJECTIVE:To investigate the effect of carboxymethyl chitosan thermosensitive hydrogel on the differentiation of bone marrow mesenchymal stem cells into neurons and the possible mechanism.METHODS:Passage 3 bone marrow mesenchymal stem cells from rats were selected and cultured in carboxymethyl chitosan thermosensitive hydrogel extracts in different concentrations (0, 50, 100, 150, 200, 500 g/L). Control cells were cultured in culture medium with no addition of carboxymethyl chitosan thermosensitive hydrogel extracts. MTT assay was performed to investigate the effects of different concentrations of carboxymethyl chitosan thermosensitive hydrogel extracts on bone marrow mesenchymal stem cell proliferation. Western blot assay was used to explore the effect of 150 g/L carboxymethyl chitosan thermosensitive hydrogel extracts on the expression of neuron-specific enolase, Nestin, Vimentin, NF-M, microtubule associated protein 2, glial fibrillary acidic protein, β3-tubulin, Notch1 and Jag1 protein.RESULTS AND CONCLUSION:MTT assay showed that carboxymethyl chitosan thermosensitive hydrogel promoted the cell proliferation, and the proliferation rate reached the peak at the concentration of 150 g/L. Western blot assay showed that the cells induced by 150 g/L carboxymethyl chitosan thermosensitive hydrogel extract had significant increases in neuron-specific enolase, Nestin, Vimentin, NF-M, microtubule associated protein 2, glial fibrillary acidic protein, and β3-tubulin protein expression, and obvious decreases in Notch1 and Jag1 protein expression in comparison with the control group. These results indicate that the carboxymethyl chitosan thermosensitive hydrogel induces rat bone marrow mesenchymal stem cells to differentiate toward neurons, and suppresses the activity of Notch signal pathway in the process of differentiation.

Mutation analysis and prenatal diagnosis for 12 families affected with hereditary hearing loss and enlarged vestibular aqueduct / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To carry out mutation analysis and prenatal diagnosis for 12 families affected with hearing loss and enlarged vestibular aqueduct from southern Zhejiang province.</p><p><b>METHODS</b>Clinical data and peripheral venous blood samples of 38 members from the 12 families were obtained. Mutations of 4 genes, namely SLC26A4, GJB2, c.538C to T and c.547G to A of GJB3, m.1555A to G and m.1494C to T of 12S rRNA, were detected by PCR and Sanger sequencing. Maternal contamination was excluded by application of STR detection during prenatal diagnosis.</p><p><b>RESULTS</b>Among the probands from the 12 families, 11 were found to be compound heterozygotes or homozygotes and 25 were heterozygotes. All of the families were detected with IVS7-2A to G mutations, and 4 had a second heterozygous mutation (c.2168A to G of the SLC26A4 gene). Four rare pathogenic mutations, namely IVS5-1G to A, c.946G to T, c.1607A to G and c.2167C to G, were detected in another four families. In addition, the partner of proband from pedigree 3 was identified with compound heterozygous mutations of c.235delC and c.299-300delAT, and proband of pedigree 5 has carried a mutation of c.109G to A in GJB2. For SLC26A4 gene, prenatal diagnostic testing has revealed heterozygous mutations in 6 fetuses and compound heterozygous mutations in 2 fetuses.</p><p><b>CONCLUSION</b>IVS7-2A to G and c.2168A to G of the SLC26A4 gene were the most common mutations in southern Zhejiang. Such mutations can be found in most families affected with hearing loss and enlarged vestibular aqueduct, which may facilitate genetic counseling and prenatal diagnosis for such families.</p>

Analysis of clinical phenotypes and GJB2 gene mutations in families affected with hearing loss from southern Zhejiang / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and pathological mutations in 44 families affected with hearing loss from southern Zhejiang, and to provide genetic counseling and prenatal diagnosis for 6 of the families.</p><p><b>METHODS</b>Microarray was employed to detect c.35delG, c.176del16, c.235delC and c.299-300delAT mutations of the GJB2 gene among 228 patients. For those carrying a single heterozygous mutation, the whole coding region of the GJB2 gene was analyzed by Sanger sequencing. For prenatal diagnosis, maternal DNA contamination was excluded by application of STR analysis.</p><p><b>RESULTS</b>The microarray assay has detected 49 patients with GJB2 mutations, which included 24 homozygous c.235delC mutations, 5 compound heterozygous c.235delC/c.176del16 mutations, 2 compound heterozygous c.235delC/c.299-300delAT mutations. Respectively, 16, 1 and 1 patients have carried single heterozygous c.235delC, c.176del16, and c.299-300delAT mutation. For the 16 patients, 7, 1, 1, 2, and 3 were detected by Sanger sequencing with a second heterozygous mutation of c.109G>A (2 of which were in conjunction with heterozygous c.176del16 and c.299-300delAT mutations), c.230G>A, c.427C>T, c.508-511 dupAACG, 79G>A+341A>G, respectively. Prenatal diagnosis revealed a compound heterozygous mutation in a fetus, heterozygous mutations in 4 fetuses, and no mutation of the GJB2 gene in 1 fetus.</p><p><b>CONCLUSION</b>The proportion of carriers for GJB2 gene mutations in patients with hearing loss from southern Zhejiang has reached 21.5%. The c.235delC, c.176del16, and compound c.299-300delAT and c.109G>A mutations can cause moderate to severe hearing loss. In most affected families, Heterozygous mutations may be identified by sequencing the whole coding region of the GJB2 gene. Genetic analysis and prenatal diagnosis can prevent birth of further affected children.</p>

Analysis of PKHD1 gene mutation in a family affected with infantile polycystic kidney disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze PKHD1 gene mutation in a family affected with autosomal recessive polycystic kidney disease (ARPKD).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral and cord blood samples obtained from the parents and the fetus. Potential mutations were identified using targeted exome sequencing and confirmed by Sanger sequencing. Pathogenicity of the mutation was analyzed using PolyPhen-2 and SIFT software.</p><p><b>RESULTS</b>Compound heterozygous mutations of c.11314C>T (p.Arg3772*) and a novel missense c.889T>A (p.Cys297Ser) of the PKHD1 gene were identified in the fetus. The mother was found to have carried the c.11314C>T mutation, while the father was found to have carried the c.889T>A mutation. PolyPhen-2 and SIFT predicted that the c.889T>A mutation is probably damaging.</p><p><b>CONCLUSION</b>A novel mutation in PKHD1 gene was detected in our ARPKD family. Compound heterozygous PKHD1 mutations were elucidated to be the molecular basis for the fetus affected with ARPKD, which has facilitated genetic counseling and implement of prenatal diagnosis for the family.</p>

Arthroscopic surgery for treatment of sinus tarsi syndrome / 中华创伤杂志

Objective To investigate the result of arthroscopic surgery in the treatment of sinus tarsi syndrome. Methods The study involved 15 patients (6 males and 9 females) with sinus tarsi syndrome admitted to First Hospital of Nanjing from July 2006 to May 2008. The age of the patients ranged from 23 to 63 years ( average 46.3 years). All the patients had one side involvement, including 10 patients with left side involvement and five with right side involvement. All the operations were performed under the tourniquet control and the patients were placed at the lateral decubitus position. The lateral, anterolateral and posterolateral portals were applied intraoperatively and the medial portal was applied when necessary. Visual analogue scale (VAS) and American orthopedic foot and ankle scale (AOFAS) ankle-hindfoot scale were used for follow-up evaluation. Results More than two lesions were found under arthroscope in all patients. The lesions included scar tissue hypertrophy and inflammation in the sinus tarsal canal, soft tissue impingement in the subtalar joint, synovitis, partial tears of subtalar capsule, interosseous talocalcaneal ligament or cervical ligament, cartilage injury and subtalar degeneration. All patients were followed up for 19-35 months (mean 26. 1 months). At the final follow-up, the VAS score was improved from preoperative 7.6 points ( range 6-9 points) to postoperative 2.5 points (range 1-4 points) (P＜0.01 ), and the AOFAS score improved from preoperative 41. 9 points (range 20-67 points) to postoperative 83. 1 points ( range 70-100 points) ( P ＜ 0. 01 ). The excellence rate of the AOFAS score reached 73% at the final follow-up. Conclusion For patients with sinus tarsi syndrome after a failed conservative treatment, arthroscopic surgery should be performed as soon as possible and the clinical result is satisfactory.