A 67-year-old female patient with postoperative recurrence of stage Ⅳright renal cell carcinoma and multiple intracranial metastases was treated with sorafenib and sintilimab.Within 2 weeks,the patient had a fever and red spotted rash in facial,back,buttocks and limb.After 2 days,the fever completely relieved,but subcutaneous exudation appeared on the skin of both elbow joints,buttocks,and outer thighs,followed by gradual epidermal lysis and detachment with skin ulceration.After 4 days,the patient's epidermolysis area was greater than 30％of the body surface area.The patient was diagnosed with toxic epidermal necrolysis(TEN).The adverse reaction correlation was assessed by ALDEN SCORE sheet.The adverse reaction of TEN was"likely"caused by sorafenib and sintilimab.After withdrawal and treatment,the TEN was cured.This paper explores the correlation between the TEN and the combination use of sorafenib and sintilimab and the management.This paper will provide reference for the early diagnosis and correct treatment of TEN.

BACKGROUND: Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23. METHODS: We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined. RESULTS: DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown. CONCLUSIONS Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP / OPN pathway.
Humans ; Osteopontin/genetics* ; Alkaline Phosphatase/metabolism* ; Receptor, Fibroblast Growth Factor, Type 3/metabolism* ; Scoliosis/genetics* ; Osteoblasts/metabolism* ; Calcinosis ; RNA, Messenger/metabolism* ; Bone Diseases, Metabolic/metabolism* ; Fibroblast Growth Factors/genetics*

Objective:To investigate the surgical strategy of posterior correction of cervicothoracic scoliosis in children and adolescents, and to analyze the curative effect of surgical correction.Methods:A retrospective study was conducted on 14 patients with cervicothoracic scoliosis who underwent surgical treatment in the department of spine surgery of our hospital from January 2014 to June 2020, including 9 female and 5 male patients. 8 patients were treated with Halo traction before surgery.Among them, 7 patients were treated by posterior column osteotomy and fusion surgery, 7 patients were treated byposterior approach hemivertebra osteotomy. The scoliosis Cobb angle, T 1 tilt angle, clavicle angle, neck tilt angle, shoulder height difference, sagittal balance distance, coronal balance distance and local kyphosis angle were measured compared among before operation, after operation, at 1 year follow-up and at the last follow-up to evaluate the effect of surgical treatment and the correction loss at follow-up. Intraoperative and postoperative complications were recorded, and the Scoliosis Research Society question naires-22 (SRS-22) questionnaire was completed preoperatively and at 24-month follow-up to evaluate the functional status and treatment effect. Results:All 14 patients successfully completed the operation, the operation time was 6.85±1.79 h (range, 5-11 h); the intraoperative blood loss was 685.71±265.61 ml (range, 400-1 200 ml), and the follow-up time was 37.28±13.75 months (range, 24-72 months). The Cobb angle of the main curve was 50.20°±15.19° preoperatively, 10.91°±6.46° postoperatively , 10.53°±6.42° at 1-year follow-up, and 10.14°±5.95° at the last follow-up, and the difference was statistically significant ( F=45.55, P<0.001), the preoperative and postoperative difference was statistically significant ( t=10.62, P<0.001) with a correction rate of 78.32%±11.41%. The T 1 inclination angle was 16.08°±8.06° before operation, 3.71°±2.40° after operation, 4.05°±1.94° at 1-year follow-up, and 3.97°±2.04° at the last follow-up, and the difference was statistically significant ( F=10.55, P=0.001), the preoperative and postoperative difference was statistically significant ( t=6.37, P<0.001) with a correction rate of 69.56%±25.86%. The neck tilt angle was 7.45°±3.72° before operation, 2.45°±1.12° after operation, 2.75°±0.89° at 1-year follow-up, and 3.10°±2.01° at the last follow-up, and the difference was statistically significant ( F=6.65, P=0.008), in which postoperative correction rate was 57.92%±25.41%, and the difference was statistically significant ( t=4.69, P<0.001). The data of shoulder height difference before operation did not conform to normal distribution (Shapiro-Wilk test, P=0.017), it was 0.97 (0.54, 1.32) cm before operation and 0.53±0.40 cm after operation, and the postoperative correction rate was 50.17%±27.38%, the difference was statistically significant ( Z=3.18, P=0.001). The total score of SRS-22 questionnaire was increased from 4.21±0.29 preoperatively to 4.81±0.17 at 24-month follow-up ( t=7.35, P<0.001). Except for one patient with transient upper limb numbness, the other 13 patients showed no obvious intraoperative or postoperative complications. Conclusion:Both posterior column osteotomy with fusion and posterior hemivertebra osteotomy are effective in the treatment of cervicothoracic scoliosis, and the surgeon can make individual treatment plans according to different conditions.

Objective:To investigate the clinical efficacy of dual growing rods (DGR) in the treatment of early onset scoliosis (EOS), and to evaluate the safety of its clinical application.Methods:From March 2015 to August 2021, a total of 20 EOS patients with onset age within 10 years old who were treated with dual growth rod technique were retrospectively analyzed, including 8 males and 12 females. The mean age of patients at first surgery was 9.0±1.4 years (range, 6.3-10.8 years); the preoperative Cobb angle was 59.0°±16.8° (range, 41.2°-103°). The Cobb angle, thoracic kyphosis angle, lumbar lordosis angle, T 1-T 12 height, T 1-S 1 height, coronal plane imbalance, sagittal vertical axis (SVA), apical vertebral translation (AVT) and Campbell's space available for lung ratio (SAL) were recorded and analyzed while surgery-related complications were also recorded. Results:The average follow-up time of 20 patients was 28.07±14.30 months. The average initial hospital stay was 20.56±8.28 days, the average initial operation time was 211.70±39.80 min, the average blood loss in the initial operation was 255.00±149.50 ml, and the average surgical distraction was 1.60±0.51 times per person. The Cobb angle of the main curve in the coronal plane decreased from 59.00°±16.80° before operation to 33.40°±11.80° after the initial operation, which was 29.67°±11.67° at 1 year and 29.40°±11.30° at the last follow-up. Preoperative thoracic kyphosis angle was 41.39°±6.06°, decreased to 31.72°±3.56° after the initial operation, was 30.32°±4.26° at 1-year and 30.24°±4.23° at the last follow-up; preoperative lumbar lordosis angle was 45.90°±8.03°, decreased to 42.65°±9.05° after initial operation, 41.55°±7.84° at 1-year follow-up, and 41.53°±8.21° at the last follow-up; preoperative T 1-S 1 height was 31.76±4.42 cm, initial after operation, it increased to 34.64±3.96 cm, 36.73±3.87 cm at 1 year, and 37.28±4.36 cm at the last follow-up; preoperative T 1-T 12 height was 17.38±2.76 cm. increased to 19.39±2.86 cm after the initial operation, 21.77±2.71 cm at 1 year, and 21.91±2.74 cm at the last follow-up; Preoperative coronal balance was 1.52±0.73 cm, and decreased to 0.87±0.38 cm after the initial operation, 0.81±0.38 cm at 1 year, and 0.77±0.37 cm at the last follow-up; preoperative sagittal balance was 1.94±0.78 cm, and 1.42±0.56 cm after operation, 1.28±0.55 cm at 1 year, and 1.26±0.57 cm at the last follow-up; The preoperative apical vertebra offset was 4.33±1.85 cm, and 2.16±1.47 cm after the initial operation, 1.63±1.17 cm at 1 year, and 1.61±1.23 cm at the last follow-up; SAL increased from preoperative 0.88±0.05 to 0.94±0.03 postoperatively, and 0.96±0.01 at 1-year follow-up, and 0.97±0.01 at the last follow-up. The differences between the above indicators before and after surgery were statistically significant ( P<0.05); there was a statistically significant difference in SAL between the 1-year follow-up and the last follow-up ( t=3.80, P=0.001), and other indicators were not statistically significant. Among the 20 cases, there were 5 cases of postoperative complications, including 2 cases of pedicle screw loosening and displacement, 2 cases of transverse process hook decoupling, and 1 case of proximal junctional kyphosis (PJK). The complication rate was 25% (5/20), all of them underwent revision treatment, and the prognosis was good after timely treatment. Conclusion:The dual growth bar technique can effectively control the progression of EOS deformity, preserve the longitudinal growth potential of the spine, and buy time for the development of the thorax in children, which has high safety.

Objective:To evaluate the feasibility and clinical efficacy of deformed complex vertebral osteotomy (DCVO) technique on the treatment of angular kyphosis of cured spinal tuberculosis.Methods:A retrospective study was performed on patients with angular kyphosis of cured spinal tuberculosis who underwent the DCVO technique or posterior vertebral column resection (PVCR) technique from Jan, 2007 to Jan, 2019. 33 patients were included, 18 males and 15 females, the average age was 39.5±15.0 years old (ranged 9-78 years old). The vertebral deformity in thoracic vertebrae 14 cases, thoracolumbar vertebrae 16 cases, and lumbar vertebrae 3 cases. 20 cases underwent the DCVO technique, while 13 cases underwent PVCR technique. For DCVO group, the multiple malformed vertebrae were considered a malformed complex, and a larger range and angle wedge osteotomy was performed within the complex using the DCVO technique. PVCR technique would resect the whole deformed vertebrae, and subsequently brought the two separated spinal columns together with instruments and titanium mesh. The intro-operative blood loss, operating time and complications were recorded. The radiological measurements included preoperative and postoperative spinopelvic parameters, which including thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and segmental kyphosis. The recovery of neurological function was evaluated by Frankle classification.Results:All patients were followed up for 7-72 months. Comparing with the cases underwent PVCR technique, the DCVO group has a significantly lower blood loss (1315.00±462.57 ml), operating time (293.00±83.86 min) and complications rate (1.5%). At the time of preoperation, postoperation and last follow-up, the deformity angle of DCVO group was 96.80°±6.32°, 29.10°±6.96°and 29.05°±6.49°, which gained an average 69.9% correction rate. The statistical analysis suggested that deformity angle was enormously corrected. And there was an insignificant difference between DCVO group and PVCR group. Meanwhile, the preoperative, postoperative and follow-up TK of DCVO group was 96.96°±29.13°, 37.15°±4.88° and 37.00°±3.89°respectively, whosecorrection rate was 67.1%; LL was 66.70°±21.21°, 42.25°±5.53° and 41.90°±4.98°, which have a significant difference between pre-operation and post-operation/follow-up ( F=23.997, P<0.001) ; SVA was 75.95±18.63 mm, 16.30±6.88 mm and 16.55±7.30 mm. PI was 47.50°±6.12°, 47.35°±5.54°and 47.90°±5.93°, PT was 37.25°±9.63°, 18.50°±1.99° and 19.00°±1.65°; SS was 10.25°±8.27°, 29.15°±5.91° and 28.85°±5.77°. The sagittal and spinopelvic parameters of two groups improved significantly at postoperation and follow-up. No obviously difference of spinal parameters was found between two groups at preoperation and postoperation. Both groups have cases with dysneuria. And all of these cases achieved different degrees of recovery at follow-up. Conclusion:The use of DCVO technique for the treatment of post-tubercular angular kyphosis is safe and efficiency. DCVO leads a better clinical outcomes and lower complication rate than VCR technique.

Objective:To investigate the accuracy and feasibility of 3D-printing individualized template-guided and CT-guided 192Ir interstitial brachytherapy in the central recurrent gynecologic tumors by comparing pre-plan and intraoperative physical dosimetric parameters. Methods:This study involved 38 patients with central recurrent gynecologic tumors who underwent 3D printing individual template (3D-PIT)-assisted and CT-guided 192Ir interstitial brachytherapy in the Department of Radiation Oncology of the Peking University Third Hospital from Jan 2018 to Dec 2019.The prescription doses for the target tumor areas were 10-36 Gy to be delivered at 5-6 Gy/fraction for 2-6 fractions.The pre-plan and intraoperative dosimetric parameters were compared, including the minimum prescription doses delivered to 90% and 100% of target volume( D90, D100)and the mean percentage of volume receiving 100% of the prescription doses ( V100). Meanwhile, the doses delivered to 2 cm 3 ( D2 cm 3) of organs at risk (bladders, rectums, and colons) were analyzed.The quality parameters of the brachytherapy were studied, including conformity index (CI), homogeneity index (HI), and external index (EI) of the target volume.Perioperative complications were also observed. Results:A total of 194 treatments were included.During the treatment, 5-13 (median 6) needles were inserted, with a prescription dose of 5-6 Gy per fraction.There were no statistical differences between pre-plan and intraoperative D90, D100, V100, CI, HI, and EI as well as the D2 cm 3 of bladders and colons at risk ( P>0.05). In contrast, for the D2 cm 3 of rectums, the intraoperative dose was slightly higher than the pre-plan dose, showing a statistical difference ( t=-0.335, P=0.027). Conclusions:The 3D-PIT-assisted and CT-guided 192Ir interstitial brachytherapy at a high dose rate is accurate and feasible in the treatment of recurrent gynecologic tumors, meeting the pre-plan dose requirement.

Objective The morphological data of the second thoracic vertebra and the third lumbar vertebra were measured by computerized tomography （CT）. The sex differences were analyzed and the discrimination equation was obtained. Methods The data of 274 adults （203 cases from experimental group and 69 cases from validation group） from central China were collected. Four linear data （maximum transverse length of vertebral body, maximum longitudinal length of vertebral body, maximum transverse length of vertebral foramen, maximum longitudinal length of vertebral foramen）, one angle data （angle between spinous processes） and two area （vertebral foramen area, total cross-sectional area of vertebral body） data of the second thoracic vertebra and the third lumbar vertebra were collected, respectively. Then three ratios ［maximum transverse length/　maximum longitudinal length of vertebral body, maximum transverse length/ maximum longitudinal length of vertebral foramen, vertebral foramen area/ （total cross-sectional area of vertebral body-vertebral foramen area）］ and one angle （angle between spinous processes） were obtained. The discriminant equation was established for sexual discriminant analysis. Results The morphology of the second thoracic vertebra and the third lumbar vertebra was related with gender. Four single index discriminant formulae and eleven multi-index discriminant formulae were established. The 69 validation group samples were substituted into the formula for testing, and the maximum discriminant accuracy rate of the single-index discriminant formula was 75%. The maximum discriminant accuracy rate of multi-index discriminant formula was 83%. Conclusion It is feasible to conduct individual sex analysis by the morphological indexes of second thoracic vertebra and the third lumbar vertebra. The indexes have important application values in practice.
China ; Female ; Lumbar Vertebrae/diagnostic imaging* ; Male ; Thoracic Vertebrae/diagnostic imaging* ; Tomography, X-Ray Computed ; Vertebral Body

INTRODUCTION: The objectives of this study were to examine the effects of ethnicity, gender and a proton pump inhibitor (PPI), omeprazole, on the human gut microbiome. PPIs are commonly used for the treatment of acid-related disorders. We hypothesised that PPI therapy might perturb microbial communities and alter the gut microbiome. METHODS: Healthy subjects of Chinese (n = 12), Malay (n = 12) and Indian (n = 10) ancestry, aged 21-37 years, were enrolled. They provided a baseline stool sample (Day 1) and were then given a course of omeprazole at therapeutic dose (20 mg daily) for seven days. Stool samples were collected again on Day 7 and 14 (one week after stopping omeprazole). Microbial DNA was extracted from the stool samples, followed by polymerase chain reaction, library construction, 16S rRNA sequencing using Illumina MiSeq, and statistical and bioinformatics analyses. RESULTS: The findings showed an increase in species richness (p = 0.018) after omeprazole consumption on Day 7, which reverted to baseline on Day 14. There were significant increases in the relative abundance of Streptococcus vestibularis (p = 0.0001) and Veillonella dispar (p = 0.0001) on Day 7, which diminished on Day 14. Faecalibacterium prausnitzii, Sutterella stercoricanis and Bacteroides denticanum were characteristic of Chinese, Malays and Indians, respectively. Lactobacillaceae and Bacteroides xylanisolvens were the signature taxa of male and female subjects, respectively. CONCLUSION The study demonstrated alterations in the gut microbiome following omeprazole treatment. This may explain the underlying pathology of increased risk of Clostridium difficile infections associated with omeprazole therapy.

OBJECTIVE: To investigate paraffin section thickness in immunohistochemical detection of p16 expression in cervical tissue samples. METHODS: p16 immunohistochemical staining was performed in 150 cases of chronic cervicitis, 126 cases of low-grade squamous intraepithelial lesions(LSIL), 96 cases of high-grade squamous intraepithelial lesions (HSIL) and 78 cases of cervical cancer from January 2014 to March 2018 in Zhongshan Boai Hospital. The results of p16 protein expression in paraffin sections with thickness of 2, 3, 4, 5 and 6 μm were compared using Logistic regression analysis. RESULTS: With the increase of slice thickness, the staining of p16 protein in nucleus gradually increased. The thickness of cervical slices in chronic cervicitis and cervical cancer samples had no significant effect on the positive rate of p16 protein(=7.817 and 1.332, both >0.05), while the thickness of slices in LSIL and HSIL samples had significant effect on the positive rate of p16 protein (=17.688 and 10.182, <0.05 or <0.01). The stable and reliable results were obtained when the slices were between 3 and 5 μm thick. CONCLUSIONS Paraffin sections with thickness of 3.0-5.0 μm are recommended for immnohistochemical staining of p16 protein in cervical tissue samples.
Biomarkers, Tumor ; genetics ; metabolism ; Cervical Intraepithelial Neoplasia ; Cyclin-Dependent Kinase Inhibitor p16 ; genetics ; metabolism ; Female ; Histocytological Preparation Techniques ; standards ; Humans ; Immunohistochemistry ; Paraffin ; Squamous Intraepithelial Lesions of the Cervix ; Uterine Cervical Neoplasms ; physiopathology

Objective To explore the role of clinical pharmacists in the treatment of neuropathic pain by using lidocaine epidural.Methods Clinical pharmacists participated in the treatment process of neuropathy pain of two cases who using lidocaine epidural,optimizing regimen,reduced the occurrence of adverse drug reactions.In the view of the treatment for patients with similar adverse reactions,clinical pharmacists through searching for literatures to get related pharmaceutical information,and then combining with the conditions of individual patients,provided evidence-based medicine support for clinical treatment,and optimized individual dosage regimen.Results and conclusion Clinical pharmacists participated in the clinical work,provided treatment suggestions from the perspective of pharmacology,improved the curative effect of drugs and reduced the occurrence of adverse drug reactions.