Objective:To explore the genetic basis for a fetus with nuchal cystic hygroma identified in the first trimester and cholecystomegaly identified in the middle trimester of pregnancy.Methods:A 27-year-old pregnant woman who had presented at the Antenatal Diagnostic Center of Jinan Maternal and Child Health Care Hospital on October 25, 2018 was selected as the study subject. Chorionic villus sampling was carried out in the first trimester for chromosomal karyotyping and SNP-Array analysis. Amniocentesis was carried out in the second trimester, and peripheral blood of the couple was collected at the same time. Trio whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:No abnormality was found by chromosomal karyotyping and SNP-Array, whilst high-throughput sequencing revealed that the fetus had harbored a heterozygous c. 7732A>T (p.K2578X) nonsense variant of the NIPBL gene. Following elected abortion, the autopsy results were consistent with features of Cornelia de Lange syndrome (CdLS). The same variant was detected in neither parents and was unreported in the literature. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as pathogenic (PVS1+ PS2+ PM2_Supporting+ PP3). Conclusion:The novel nonsense variant of the NIPBL gene probably underlay the genetic etiology of CdLS in this fetus. Above finding has also enriched the mutational spectrum of the NIPBL gene.

Diffuse large B cell lymphoma （DLBCL） is a malignant tumor derived from mature B cells. Currently， chemotherapy is still the main clinical treatment. However， some patients experience recurrence or refractory conditions after treatment. On June 15， 2023， the FDA approved the marketing of glofitamab， a CD3/CD20 bispecific monoclonal antibody， to provide the new treatment plan for patients with recurrent or refractory DLBCL after receiving 2-line or above systemic treatment. This article reviews pharmacological effects， clinical studies， safety， usage and dosage of glofitamab. Glofitamab mainly plays a therapeutic role in DLBCL by promoting the activation and proliferation of T cells，activating T cells to release tumor cell-killing proteins， and mediating the lysis of B cells. Clinical studies have shown that glofitamab has a better complete and objective response rate for recurrent or refractory DLBCL. Common adverse reactions caused by glofitamab include mild/moderate cytokine release syndrome， musculoskeletal pain， rash， fatigue， and so on，without significant drug interactions.

Objective:To evaluate the effect of orexin A on morphine-induced gastrointestinal dysfunction in mice.Methods:Forty SPF C57B/6 mice, aged 6-8 weeks, half male and half female, weighing 18-22 g, were divided into 5 groups ( n=8 each) using a random number table method: control group (group C), morphine group (group M) and morphine + different doses of orexin A groups (MOH, MOM and MOL groups). Normal saline 8 ml/kg was subcutaneously injected daily in group C, morphine 6 mg/kg was subcutaneously injected daily in the other four groups, and orexin A 75, 50 and 25 μg/kg were subcutaneously injected daily for 10 days at the same time in MOH, MOM and MOL groups.The fetal water content was calculated and averaged daily.After the last administration, the mice were gavaged with black nutrient paste, and the gastric emptying rate and small intestinal propulsion rate were detected 30 min later.Blood samples were collected from the orbit, and the concentration of serum gastrin (GAS) was detected by enzyme-linked immunosorbent assay.The mice were then sacrificed, and colon tissues were removed for determination of c-kit positive cell area (by immunohistochemistry) and expression of c-kit, substance P (SP) and neural nitric oxide synthase (nNOS) in colon tissues (by Western blot). Results:Compared with group C, the rate of fecal water content, gastric emptying rate, small intestinal propulsion rate and serum GAS concentration were significantly decreased, the area of c-kit positive cells was decreased, and the expression of c-kit and SP was down-regulated, and the expression of nNOS was up-regulated in group M ( P<0.05). Compared with group M, the small intestinal propulsive rate and serum GAS concentration were significantly increased, and the area of c-kit positive cells was increased, and the expression of c-kit was up-regulated in group MOH, the rate of fecal water content, gastric emptying rate, small intestinal propulsion rate and serum GAS concentration were significantly increased, the area of c-kit positive cells was increased, and the expression of c-kit and SP was up-regulated, and the expression of nNOS was down-regulated in group MOM, and the serum GAS concentration and c-kit positive cell area were significantly increased in group MOL ( P<0.05). Conclusions:Orexin A 50 μg/kg can effectively alleviate the gastrointestinal dysfunction induced by morphine in mice, and the mechanism may be related to promotion of GAS secretion, interstitial cells of Cajal growth and SP release and inhibition of NO release.

Objective:To explore the curative effects of individualized surgical method for treating pyriform sinus fistula (PSF) in children.Methods:A total of 43 PSF children treated in the Department of Pediatric Surgery of Henan Provincial People′s Hospital from June 2015 to November 2019 were selected, with 41 cases on the left side and 2 cases on the right side.There were 27 cases in the quiescent inflammatory infection stage and 16 cases in the acute inflammatory infection stage.According to patients′ condition, low-temperature plasma radiofrequency ablation, fistulectomy, abscess incision and drainage or combined operation were conducted.The postoperative complications and recurrence were observed.Results:Among 43 cases, there were 19 cases treated with low-temperature plasma radiofrequency ablation, 11 cases treated with low-temperature plasma radiofrequency ablation combined with abscess incision and drainage, 5 cases treated with low-temperature plasma radiofrequency ablation combined with fistulectomy, and 8 cases treated with fistulectomy.Four cases had postoperative hoarseness and recovered within 1-5 months.One case occurred pseudo healing after abscess incision and drainage, and healed after incision and debridement.Totally, 4 cases recurred, and the follow-up time was from 3 months to 57 months.Conclusions:Low-temperature plasma radiofrequency ablation has the advantages of minimally invasive, safe and effective, which provides a new treatment for PSF in children.Based on the condition of children, the choice of individualized treatment can significantly improve the curative effects.

Objective:To explore the strategy of selecting the second stage operation after neonatal enterostomy.Methods:Clinical data of 35 cases admitted to the Department of Pediatric Surgery of Henan Provincial People′s Hospital for enterostomy in neonatal period and radical operation in the second stage from May 2014 to December 2019 were subject to retrospective analysis.They were inquired about the medical history in detail before the operation, and received barium enema and colonoscopy, 24-hour delayed radiography, anorectal manometry and other examinations.During the operation, a multi-point intestinal biopsy and rapid frozen pathological examination were performed accor-ding to the individual′s condition, and the specific surgical method was determined in combination with intraoperative exploration.Postoperative observations were conducted for such complications as anastomotic leakage, intestinal obstruction, and abdominal infection, as well as such medium and long-term outcomes as intestinal function recovery, defecation, and nutritional status.Results:Nine cases were diagnosed with neonatal necrotizing enterocolitis (NEC) and received ostomy closure.Sixteen cases were diagnosed with NEC concomitant with intestinal stenosis and received the narrow bowel enterectomy and anastomosis combined with ostomy closure; 10 cases were diagnosed with Hirschsprung′s disease, including 5 cases of total colonic aganglionosis treated with Soave radical operation, 3 cases of long-segment Hirschsprung′s disease treated with subtotal colectomy, inverted ascending coloanal anastomosis with Deloyers method and second enterostomy, and 2 cases of normal-segment Hirschsprung′s disease treated with pull-through operation combined with ostomy closure.After the operation, 1 case had anastomotic leakage and septic shock, 1 case had incision dehiscence, 3 cases had adhesive intestinal obstruction and 1 case occurred left lung consolidation.During a follow-up period of 3-36 months, their recovery condition was acceptable.Conclusions:For those neonates receiving enterostomy, detailed medical history should be enquired before the second stage operation.The combination of barium enema and colonoscopy, 24-hour delayed radiography and multi-point intestinal biopsy with intraoperative exploration conduced to selecting appropriate individualized surgical schemes and reducing surgical complications, thus improving the long-term quality of life of children.

Objective:To explore the application value of 3D printing technology in the precise resection of pediatric retroperitoneal neuroblastoma(NB).Methods:Eleven patients with retroperitoneal NB admitted to the Department of Pediatric Surgery of Henan Provincial People′s Hospital from March 2017 to December 2019 were selected in this study, and all of them received preoperative plain and enhanced computed tomography (CT) scanning of whole abdomen.The original data were imported into the mimics 20 software for processing.The tumor and important peripheral blood vessels were reconstructed with such commands as multi-layer edition, threshold adjustment, regional growth and 3D edition to output the standardized 3D printing stl format file and print out the tumor model by 3D printer.Based on the 3D reconstruction results, the precise surgical planning was performed to determine the optimal operative scheme.The data of all cases were analyzed retrospectively.The parents of these children were investigated by questionnaire and the results were statistically analyzed.Results:All 11 patients successfully underwent the operation under the planning of 3D printing technology.Nine of them had complete tumor resection and 2 cases had palliative resection.The operation time ranged from 140 min to 750 min, with an average of 210 min; the bleeding volume ranged from 100 mL to 1 500 mL, with an average of 240 mL; the postoperative pathological reports revealed that 9 children had NB and 2 cases had ganglioneuroblastoma.There was no case of perioperative death.There were 2 cases of postoperative complications, including 1 case of severe diarrhea with chylous leakage, which was relieved after the treatment of parenteral nutrition and somatostatin, and 1 case of left lower extremity weight-bearing difficulty after left iliac artery anastomosis, which was improved after rehabilitation physical therapy.The follow-up time ranged from 1 month to 30 months.There were 2 cases recurred in the original operation area.One patient received reoperation after chemotherapy; the other continued chemotherapy in progress.As for the 2 cases of palliative resection, they received chemotherapy and survived with tumor.After using 3D model to communicate with children′s parents, their awareness rate of disease, operation mode and postoperative complications were significantly higher than that of CT.Conclusions:3D printing technology can accurately evaluate the structural relationship between retroperitoneal NB and important peripheral blood vessels in children, which contributes to improving the parents′ cognition of the operation mode, and is conducive to selecting the optimal operation scheme and achieving precise tumor resection.

OBJECTIVE: To observe the application of modified traction therapy in traumatic atlantoaxial subluxation in adults. METHODS: The clinical data of 31 patients with atlantoaxial subluxation treated from March 2018 to June 2019 were restropectively analyzed. There were 15 males and 16 females, aged from 18 to 68 years old with an average of 39 years old, including 10 cases of 18-40 years, 15 cases of 41-60 years, 6 cases of 51-68 years. The main manifestations of the patients were limited neck movement, pain, and atlantoaxial CT scan showed different degrees of atlantoaxial subluxation. Three dimensional multifunctional traction bed was used for traction for 2 min, relaxation for 10 s. The traction angle starts from the rearward extension of 5°-10° and weight from 3-6 kg. The weight increased by 1 kg every two days until the symptoms were improved. Traction time was 30 min twice a day and 10 days for a course of treatment. One course of treatment was performed in patients with 1-2 mm left and right equal width of atlantoaxial space, and two courses of treatment were performed in patients with 3-4 mm left and right equal width of atlantoaxial space, and the course of treatment could be increased to 3 months in especially patients with serious problems, such as 4 mm left and right equal width of atlantoaxial space and no improvement after conventional treatment. The criteria to evaluate the clinical effect was cure:no pain in the neck, normal range of neck movement, CT showed normal atlantoaxial space and odontoid process was in the middle, patients with normal neck movement were followed up 1 month after the end of treatment;improvement:neck pain was significantly improved and CT showed that the left and right atlantoaxial space was less than 1 mm in equal width. RESULTS: Among the 31 patients, 17 cases were cured by one course of treatment, 11 cases were cured by 2 courses of treatment, and 2 caseswere improved. CONCLUSION The modified traction therapy has obvious effect on adult traumatic atlantoaxial subluxation, especially the subluxation of 3-4 mm equal width in left and right atlantoaxial space, and this method is safe and reliable with good efficacy and the patients without discomfort.
Adolescent ; Adult ; Aged ; Atlanto-Axial Joint ; Female ; Humans ; Joint Dislocations ; Male ; Middle Aged ; Odontoid Process ; Spinal Fusion ; Traction ; Young Adult

Objective:To investigate the effect of oblique lateral lumbar intervertebral fusion (OLIF) on inflammatory factors in patients with degenerative spinal canal stenosis (DLSS).Methods:Retrospective analysis of clinical data of 64 DLSS patients in the department of orthopedics, Jizhong Energy Fengfeng Group Hospital from June 2016 to June 2018 was performed. There were 35 males and 34 females, aged (60.70±6.27) years, and the age range was 20 to 80 years. According to the different surgical methods, they were divided into posterior decompression and internal fixation fusion (PLIF) group ( n=32) and OLIF group ( n=32). The coperation time, intraoperative bleeding volume, postoperative bed rest time, hospitalization time , the back and leg pain visual analogue score (VAS) , Japanese Orthopaedic Association(JOA) score of lumbar vertebrae and serum inflammatory factors [tumor necrosis factor-alpha(TNF-α), interleukin-1alpha(IL-1α), C-reactive protein(CRP)] were observed at preoperative, 3 months and last follow-up. Follow-up using outpatient examination and telephone interview was performed and survial up to March 2019. Measurement data were expressed as mean±standard deviation ( Mean± SD), comparison between groups was performed using independent sample t test or analysis of variance of repeated measurement data. Internal comparisons were performed using paired t tests. Count data were expressed as percentage (%), and χ2 test was used. Results:There was no significant difference in operation time between OLIF group and PLIF group ( P>0.05). In OLIF group, the amount of blood loss (119.72±30.41) mL, bedridden time (2.16±0.35) d and postoperative hospital stay (5.18±2.06) d were significantly lower than that of PLIF group[(318.26±94.62) mL, (3.17±0.54) d, (7.35±1.24) d], the differences between the two groups were statistically significant( P<0.05). All patients were followed for 8 months. The 3 months after operation and last follow-up, the VAS scores of back pain in OLIF group [(1.93±0.54) scores, (1.74±0.63) scores]were significantly lower than that in PLIF group [(4.05±0.62) scores, (3.87±0.74) scores]. The VAS scores of leg pain in OLIF group [(1.56±0.71) scores, (1.37±0.52) scores] were significantly lower than that of PLIF group [(3.74±0.79) scores, (2.53±0.59) scores]. The JOA scores of lumbar vertebrae in PLIF group [(22.57 ±1.83) scores, (24.38±1.65) scores] were significantly higher than that of PLIF group [(20.35±1.78) scores, (22.14±1.35) scores], the differences between the two groups were statistically significant( P<0.05). At 3 months after operation, the levels of serum TNF-α(16.95±3.92) ng/L, IL-1α(9.17±3.78) ng/L and CRP (1.97±0.24) mg/L in OLIF group were significantly lower than those in PLIF group [(20.46 ±4.27) ng/L, (11.51±4.25) ng/L, (2.36±0.32) mg/L]. Last follow-up, the level of serum TNF-α(13.47±3.54) ng/L, IL-1α(6.52±2.09) ng/L and CRP (1.42±0.16) mg/L in the OLIF group were significantly lower than those in the PLIF group [(18.08±3.84) ng/L, (8.73±5.43) ng/L, (2.04±0.25) mg/L], the differences between the two groups were statistically significant ( P<0.05). Conclusion:Compared with PLIF, OLIF can reduce the amount of intraoperative bleeding, shorten the recovery time, reduce the expression of inflammatory factors and improve the prognosis of patients with DLSS.

Objective:To analyze the mutation sites and characteristics of phospholipase CE1( PLCE1) gene in children with primary nephrotic syndrome(PNS) in Zhuang, Guangxi, China, so as to explore the expression status of PLCE1 protein in peripheral blood of PNS patients. Methods:(1)Blood samples of 154 Zhuang children with PNS and 98 healthy children of Zhuang nationality from July 2015 to September 2017 in Affiliated Hospital of Youjiang Medical College for Nationalities were collected to sequence PLCE1 gene with FastTarget target gene capture method in the combination with next generation sequencing.Based on the comparison between mutation results and information from the database, the pathogenicity, phenotype and distribution characteristics of these mutation sites were discovered and appraised.(2)The concentration of PLCE1 protein in serum samples were measured by enzyme-linked immuno sorbent assay, then the data of PNS group and healthy control group were compared and analyzed statistically with SPSS 25.0. Results:(1)A total of 18 low-frequency mutations of PLCE1 were observed, 5 of them(c.670C>T, c.578T>C, c.923G>T, c.4916C>T, and c. 5927_5929del) were found only in the PNS group, and 3 of them occurred in both PNS group and healthy control group: c.176C>T, c.389T>C, and c. 4304C>T.Five newly discovered mutations (c.923G>T, c.958T>A, c.1151C>T, c.2341A>G, and c. 3592G>C)were discovered and only c. 923 G>T is pathogenic mutation of PLCE1.(2)The concentration of PLCE1 protein in healthy control group was 414.65 (231.20, 729.81) ng/L and the level of PLCE1 in PNS group was 237.84 (116.14, 535.85) ng/L, ( Z=-3.212, P<0.001), and the value of PNS group was lower than that in the healthy control group. Conclusions:(1)As a new pathogenic mutation of PLCE1, c.923G>T was found.(2)The phenotype of PLCE1 gene mutation in Zhuang children with PNS was diverse, and they may differ by race and region.(3) PLCE1 protein of serum may act as a protective protein to guarantee various life activities of cells by participating in multiple signal transduction pathways.

Objective:To investigate the clinical effects of perforator flaps in the repair of limb defects.Methods:Anterolateral thigh perforator flap (ALTP), deep inferior epigastric perforator flap (DIEP), posterior in- terosseous artery perforator flap (PIAP), thoracodorsal artery perforator flap (TDAP), medial sural artery perforator flap (MSAP) and radial collateral artery perforator flap (RCAP) were used to repair 56 cases of limb wounds from Novem- ber, 2016 to October, 2018. The sizes of soft tissue defect were ranged from 1.5 cm×1.5 cm to 10.0 cm×24.0 cm, while the sizes of flap were ranged from 2.0 cm×2.0 cm to 11.0 cm×25.0 cm. The recipient sites were all sutured di- rectly. The flaps survived and wound healing were observed postoperatively. Appearance, texture, recovery of the limb function, shape and function of donor site were followed-up regularly.Results:One case of venous crisis occurred on the 3rd day after inferior epigastric artery perforator flap surgery, and survived after exploratory surgery with the necrosis in the distal part of the flap, which healed after dressing. Other 55 flaps all survived. Both recipient site and donor site healed in primary union. The color of the flaps was normal. The skins were soft, and the functions of the limbs recovered well. Only a linear scar remained in the donor area without dysfunction.Conclusion:The perforator flap surgery is reliable for limbs repair and can be promoted and applied.