A New Nomogram for Predicting the Risk of Intracranial Hemorrhage in Acute Ischemic Stroke Patients After Intravenous Thrombolysis.

Background: We aimed to develop and validate a new nomogram for predicting the risk of intracranial hemorrhage (ICH) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). Methods: A retrospective study enrolled 553 patients with AIS treated with IVT. The patients were randomly divided into two cohorts: the training set (70%, n = 387) and the testing set (30%, n = 166). The factors in the predictive nomogram were filtered using multivariable logistic regression analysis. The performance of the nomogram was assessed based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA). Results: After multivariable logistic regression analysis, certain factors, such as smoking, National Institutes of Health of Stroke Scale (NIHSS) score, blood urea nitrogen-to-creatinine ratio (BUN/Cr), and neutrophil-to-lymphocyte ratio (NLR), were found to be independent predictors of ICH and were used to construct a nomogram. The AUC-ROC values of the nomogram were 0.887 (95% CI: 0.842-0.933) and 0.776 (95% CI: 0.681-0.872) in the training and testing sets, respectively. The AUC-ROC of the nomogram was higher than that of the Multicenter Stroke Survey (MSS), Glucose, Race, Age, Sex, Systolic blood Pressure, and Severity of stroke (GRASPS), and stroke prognostication using age and NIH Stroke Scale-100 positive index (SPAN-100) scores for predicting ICH in both the training and testing sets (p < 0.05). The calibration plot demonstrated good agreement in both the training and testing sets. DCA indicated that the nomogram was clinically useful. Conclusions: The new nomogram, which included smoking, NIHSS, BUN/Cr, and NLR as variables, had the potential for predicting the risk of ICH in patients with AIS after IVT.

5P Strategies for Management of Multiple Endocrine Neoplasia Type 2: A Paradigm of Precision Medicine.

Multiple endocrine neoplasia type 2 (MEN2) is a neuroendocrine cancer syndrome characterized by medullary thyroid carcinoma, in combination or not with pheochromocytoma, hyperparathyroidism, and extra-endocrine features. MEN2 syndrome includes two clinically distinct forms subtyped as MEN2A and MEN2B. Nearly all MEN2 cases are caused by germline mutations of the RET proto-oncogene. In this review, we propose "5P" strategies for management of MEN2: prevention, prediction, personalization, psychological support, and participation, which could effectively improve clinical outcomes of patients. Based on RET mutations, MEN2 could be prevented through prenatal diagnosis or preimplantation genetic testing. Identification of pathogenic mutations in RET can enable early diagnosis of MEN2. Combining RET mutation testing with measurement of serum calcitonin, plasma or urinary metanephrine/normetanephrine, and serum parathyroid hormone levels could allow risk stratification and accurately prediction of MEN2 progression, thus facilitating implementation of personalized precision treatments to increase disease-free survival and overall survival. Furthermore, increased awareness of MEN2 is needed, which requires participation of physicians, patients, family members, and related organizations. Psychological support is also important for patients with MEN2 to promote comprehensive management of MEN2 symptoms. The "5P" strategies for management of MEN2 represent a typical clinical example of precision medicine. These strategies could effectively improve the health of MEN2 patient, and avoid adverse outcomes, including death and major morbidity, from MEN2.

Incomplete Ear Amputation.

Ear amputations are common in emergency departments as the auricle's protrusion from the lateral aspect of the head makes it particularly susceptible to trauma. Of the numerous approaches for auricle injuries, the classic methods include microsurgical replantation, primary reattachment, composite graft, retroauricular pocket principle, secondary reconstruction with rib cartilage, and methods using postauricular flap. The success of the operation depends largely on choosing the appropriate surgical procedure since many factors can influence surgical outcome. There is no 1 gold standard technique to treat the variety of auricle injuries. Inappropriate choice of surgical approach can be detrimental to subsequent reconstructive surgery. Therefore, the initial choice of optimal surgical approach is particularly important. In this article, a rare report of left subtotal ear laceration with inferior lobule pedicle by nonmicrosurgical primary reattachment was presented. The operation obtained an ideal cosmetic effect.

Application of the 3D digital ostectomy template (DOT) in mandibular angle ostectomy (MAO).

BACKGROUND: Mandibular angle ostectomy (MAO) is a standard approach in reconstruction of facial contour that is commonly used in East Asian patients with prominent mandibular angles (PMA). MAO is commonly performed via an intraoral approach to reduce scar visibility and risk of facial nerve injury. Since this intraoral approach for MAO has limited visual guidance during the procedure, plastic surgeons often perform the operation based on personal clinical experience. Therefore, we designed a 3D digital ostectomy template (DOT) for guidance during surgery to improve the accuracy and safety of MAO. METHODS: 10 female patients (average age 25.3 years) with PMA were enrolled in this study from August 2014 to October 2015. The DOTs were designed and printed preoperatively and utilized in the operation to guide the osteotomy. The excised mandibular angle bone and the DOTs were measured respective to each other. The data were analyzed to verify the feasibility and safety of the DOT. RESULTS: All of the patients were satisfied with the surgical results, and no complications such as fracture, hemorrhage and infection occurred. The distance from gonion (Go) along inferior margin of mandible forward to the distal end of the excised bone is "a". The distance from Go along posterior margin of ramus upward to the distal end of the excised bone is "b". The widest distance from Go to the ostectomy line is denoted by "c". Similarly, the corresponding distance in the DOT is denoted by "a'", "b'", "c'". The statistical results showed that left a vs a', b vs b', c vs c' was 63.27 ± 6.39 mm vs 62.97 ± 6.30 mm (p > 0.05), 23.98 ± 2.25 mm vs 21.83 ± 2.27 mm (p < 0.05), 13.58 ± 2.24 mm vs 13.37 ± 2.14 mm (p > 0.05), respectively. The right a vs a', b vs b', c vs c' was 62.92 ± 5.00 mm vs 62.72 ± 4.99 mm (p > 0.05), 24.03 ± 1.88 mm vs 21.80 ± 1.91 mm (p < 0.05), 13.36 ± 1.70 mm vs 13.22 ± 1.72 mm (p > 0.05), respectively. The results indicate a significant difference between b and b' both on the right and left sides. CONCLUSION: Through the application of DOT in MAO, the accuracy and safety of the operation were improved significantly. Unfortunately, the osteotomy could not be guided well in the posterior rim of the ramus. Further improvements in the surgical template are needed for application in PMA associated with oversized chin deformity or in PMA associated with large mandibular angle and severe involution.

Identification of significant biomarkers and pathways associated with gastric carcinogenesis by whole genome-wide expression profiling analysis.

The incidence of gastric cancer (GC) is extremely high in East Asia. GC is also one of the most common and lethal forms of cancer from a global perspective. However, to date, we have not been able to determine one or several genes as biomarkers in the diagnosis of GC and have also been unable to identify the genes which are important in the therapy of GC. In this study, we analyzed all genome-wide expression profiling arrays uploaded onto the Gene Expression Omnibus (GEO) database to filtrate the differentially expressed genes (DEGs) between normal stomach tissues and GC tissues. GSE13911, GSE19826 and GSE79973 were based on the GPL570 platform, and GSE29272 was based on the GPL96 platform. We screened out the DEGs from the two platforms and by selecting the intersection of these two platforms, we identified the common DEGs in the sequencing data from different laboratories. Finally, we obtained 3 upregulated and 34 downregulated DEGs in GC from 384 samples. As the number of downregulated DEGs was greater than that of the upregulated DEGs, functional analysis and pathway enrichment analysis were performed on the downregulated DEGs. Through our analysis, we identified the most significant genes associated with GC, such as secreted phosphoprotein 1 (SPP1), sulfatase 1 (SULF1), thrombospondin 2 (THBS2), ATPase H+/K+ transporting beta subunit (ATP4B), gastric intrinsic factor (GIF) and gastrokine 1 (GKN1). The prognostic power of these genes was corroborated in the Oncomine database and by Kaplan-Meier plotter (KM-plotter) analysis. Moreover, gastric acid secretion, collecting duct acid secretion, nitrogen metabolism and drug metabolism were significantly related to GC. Thus, these genes and pathways may be potential targets for improving the diagnosis and clinical effects in patients with GC.

Management of Talar Component Subsidence.

Component subsidence has been found to be the top complication that leads to failure of the total ankle arthroplasty (TAA). The cause of subsidence formation is unclear, and is multifactorial. Talar subsidence is more frequently met than tibial subsidence, and the subsequent big bone loss is demanding to handle. As a revision treatment option, neither a revision TAA nor a salvage ankle and/or hindfoot arthrodesis procedure is easy to perform or can obtain a definite outcome. The Salto XT can be used to treat most of the TAA systems available for use in the United States with acceptable short-term outcomes.

Targeted sequencing identifies a novel SH2D1A pathogenic variant in a Chinese family: Carrier screening and prenatal genetic testing.

X-linked lymphoproliferative disease type 1 (XLP1) is a rare primary immunodeficiency characterized by a clinical triad consisting of severe EBV-induced hemophagocytic lymphohistiocytosis, B-cell lymphoma, and dysgammaglobulinemia. Mutations in SH2D1A gene have been revealed as the cause of XLP1. In this study, a pregnant woman with recurrence history of birthing immunodeficiency was screened for pathogenic variant because the proband sample was unavailable. We aimed to clarify the genetic diagnosis and provide prenatal testing for the family. Next-generation sequencing (NGS)-based multigene panel was used in carrier screening of the pregnant woman. Variants of immunodeficiency related genes were analyzed and prioritized. Candidate variant was verified by using Sanger sequencing. The possible influence of the identified variant was evaluated through RNA assay. Amniocentesis, karyotyping, and Sanger sequencing were performed for prenatal testing. We identified a novel de novo frameshift SH2D1A pathogenic variant (c.251_255delTTTCA) in the pregnant carrier. Peripheral blood RNA assay indicated that the mutant transcript could escape nonsense-mediated mRNA decay (NMD) and might encode a C-terminal truncated protein. Information of the variant led to success prenatal diagnosis of the fetus. In conclusion, our study clarified the genetic diagnosis and altered disease prevention for a pregnant carrier of XLP1.

Efficacy of Calcaneus Osteotomy for Treatment of Symptomatic Müller-Weiss Disease.

BACKGROUND: Various methods of midfoot and hindfoot arthrodesis for treating symptomatic Müller-Weiss disease (MWD) have been reported in the literature. In this study, we present the results of a previously unreported method of treatment using a calcaneal osteotomy incorporating a wedge and lateral translation. METHODS: Thirteen patients (14 feet) with MWD were treated with a calcaneal osteotomy and retrospectively reviewed. These included 7 females and 6 males, with an average age of 56 years (33-79 years), and an average symptoms duration of 10.6 years (1-16 years). The disease was staged according to Maceira, which included 5 feet in stage II, 4 feet in stage III, 4 feet in stage IV, and 1 foot in stage V. Pre- and postoperative visual analog scale (VAS) score, American Orthopaedic Foot & Ankle Society (AOFAS), radiologic examination, and patients' satisfaction rate of the surgery were evaluated at an average of 3.7 years (range, 1-8.5 years) following surgery. RESULTS: The final follow-up visit showed satisfactory outcomes, with VAS score reducing from the preoperative 8 (7-9) to postoperative 2 (0-4), whereas the AOFAS score improved from the preoperative 29 (20-44) to the postoperative 79 (70-88). The patient's subjective ratings showed excellent results in 4 feet, good results in 8 feet, and fair outcomes in 2 feet. The hindfoot range of motion remained unchanged, as did the extent of the navicular complex arthritis, and no patient required an arthrodesis since surgery. CONCLUSION: A calcaneal osteotomy can be used as an alternative treatment option for selected MWD patients regardless of the radiologic stage of the disease. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Managing Complications of Percutaneous Surgery of the First Metatarsal.

The percutaneous osteotomy based on a Hohmanntype first metatarsal subcapital linear osteotomy was introduced into Mainland China in the late 1980s. No internal fixation is used for stabilization of the osteotomy, leading unfortunately to unpredictable results. Despite its high acceptance by patients and enthusiasm by surgeons at present, the clinical outcomes of percutaneous surgery have not been promising. The authors have no experience of performing this osteotomy and report only on their management of the complications of this technique and their recommended treatment algorithm.

[Clinical effect of arthroscopy-assisted minimally invasive management of bunion].

OBJECTIVE: To evaluate the effect of arthroscopy-assisted minimally invasive management of bunion and hallux valgus deformities. METHODS: Total 50 patients (53 feet) with bunion and hallux valgus deformities were treated under arthroscopy from July 2008 to July 2011, with an average age of 42.3 years old (ranging from 30 to 65 years old) involving 19 left feet, 28 right feet and 3 both feet. The American Orthopedic Foot and Ankle Society (AOFAS) hallux metatarsophalangeal-interphalangeal(MP-IP) Scale Score was used to evaluate the therapeutic effect. RESULTS: There were no complications such as hallux varus, hallux rigid and nerve or blood vessel injury. Clinically, AOFAS MP-IP Scale Score was increased from 62.19 ± 6.01 preoperatively to 88.26 ± 6.81 postoperatively. CONCLUSION: Arthroscopy-assisted minimally invasive management appears to be a good procedure with advantages of less complication, little trauma and early rehabilitation for bunion and hallux valugs deformities.

[Clinical observation of arthroscopic debridement for acute gouty arthritis of the ankle].

OBJECTIVE: To evaluate the effects of arthroscopic debridement for acute gouty arthritis of the ankle. METHODS: Forty-one patients with acute gouty arthritis of the ankle were treated under arthroscopy from January 2010 to June 2012. All the patients were male, age in ranging from 28 to 69 years with an average of 43 years. Eighteen patients were in the left ankles and 23 in the right ankles; 12 cases were firstly attack and 29 cases were recurrent attack. Course of disease was from 2 weeks to 30 months. The American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale score was used to evaluate the clinical effects. Number of acute attacks of gouty arthritis were observed. RESULTS: All the patients were followed up at least 12 months. The mean AOFAS Ankle-Hindfoot Scale score increased from 58.44 +/- 9.45 preoperatively to 86.15 +/- 7.36, 83.41 +/- 9.22, 84.10 +/- 8.22 postoperatively at 6, 12, months and the last follow-up respectively. Swelling of the ankle were improved significantly, pain was relieved and the mean number of acute attacks of gouty arthritis decreased significantly. CONCLUSION: Arthroscopy is helpful for the diagnosis of acute gouty arthritis of the ankle and improvement of clinical symptoms and ankle function.

Short-term MyD88 inhibition ameliorates cardiac graft rejection and promotes donor-specific hyporesponsiveness of skin grafts in mice.

Recognition of evolutionarily conserved ligands by Toll-like receptors (TLRs) triggers signaling cascades in innate immune cells to amplify adaptive immune responses. Nearly all TLRs require MyD88 to transduce downstream signaling. MyD88 deficiency has been shown to promote the allograft acceptance in mice. However, direct evidence for therapeutic potential of MyD88 inhibitors remains lacking. Herein, we used a MyD88 inhibitor, namely ST2825, to explore its therapeutic potential and mechanisms in fully allogeneic skin and heart transplant models. Phenotypic maturation of dendritic cells stimulated by TLR ligands was alleviated by ST2825 in parallel with reduced T-cell proliferation in vitro. A short-course treatment with ST2825 significantly prolonged cardiac graft survival (mean survival time = 18.5 ± 0.92 days vs. 7.25 ± 0.46 days). ST2825-treated group had significantly reduced proinflammatory cytokines in allografts compared with control group. ST2825 combined with anti-CD154 induced long-term skin allograft acceptance in about one-third of recipients (>100 days). 'Skin-tolerant' recipients showed attenuated donor-specific IFN-γ responses, intact IL-4 responses, and compromised alloantibody responses. We conclude that MyD88 inhibitor ST2825 attenuates acute cardiac rejection and promotes donor-specific hyporesponsiveness in stringent skin transplant models. The direct evidence suggests that pharmacological inhibition of MyD88 hold promising potential for transplant rejection.

[Clinical classification of gluteal muscle contracture under arthroscopy].

OBJECTIVE: To explore clinical effects of gluteal muscle contracture and minimum invasive surgery under the arthroscopy. METHODS: Totally 358 patients with gluteus contracture were treated,which included 175 males and 183 females with an average age of (19.7 +/- 6.8) years old (ranged, 14 to 41). All patients have a history of repetitive intramuscular injection of penicillin with benzyl alcohol solvent. According to clinical characteristics and intraoperative situation, patients were classified into four groups:cable strip (118 cases), fanshaped (107 cases), mixed (87 cases), tensor fasciae latae contracture(46 cases). The curative effects were evaluated according to postoperative function evaluation standard of gluteus contracture. RESULTS: All patients were followed up and 37 cases withdrew. The following up time ranged from 1.5 to 8 years with an average of 3.5 years. According to evaluation standard of gluteus contracture, 303 cases got excellent results, 13 cases good,and 5 cases fair at the final follow-up. No recurrence, infection and neurovascular injury occurred. CONCLUSION: The classification of gluteal muscle contracture is beneficial for choose surgical strategy and improve curative effect. The advantage of plasma knife minimally invasive solution in treating gluteal muscle contracture with radiofrequency under arthroscopy is minimally invasive, safe, and benefit for early functional exercises.

[Arthroscopic reconstruction of anterior cruciate ligament with preservation of the remnant bundle].

OBJECTIVE: To evaluate clinical effects of arthroscopic anterior cruciate ligament (ACL) reconstruction with preservation of the remnant bundle. METHODS: From January 2002 to December 2009, 57 patients with ACL partial rupture were treated with preservation of the remnant bundle. There were 39 males and 18 females, with an average age of 28.5 years old (ranged, 16 to 49 years old). Thirty-three patients had injuries in the left knees,and 24 patients had injuries in the right knees. Forty patients had injuries caused by sports, 7 patients had injuries caused by traffic accidents and 10 patients had injuries caused by daily sprain. The anterior drawer test showed positive results in 23 patients, weakly positive results in 6 cases; Lachman test showed positive results in 19 patients, and weakly positive in 4 patients. Both anterior drawer test and Lachman test showed positive results in 5 patients; and valgus stress test (medial) showed positive results in 24 patients. The mean value of Rolimeter measurement was 8.7 mm, (ranged, 7.5 to 11.5 mm). The mean International Knee Documentation Committee (IKDC) score was 70.0 +/- 7.5 and the Lysholm score was 68.0 +/- 6.3. The duration from injury to surgery was 1 week to 12 months,with an average of 3.1 months. RESULTS: There were 32 patients treated with anteromedial bundle reconstruction and 25 patients treated with poterolateral bundle reconstruction. Fifty-seven patients were followed up, and the mean follow-up time was 22.5 months (ranged, 13 to 37 months). The anterior drawer test and Lachman test were all negative at 1 month post-operation. At the end of the follow-up, the range of motion of all the knees was 120 to 130 degree. There were 54 patients with negative results of anterior drawer test and Lachman test, 1 with weakly positive result of anterior drawer test and 2 with weakly positive results of Lachman test. The measurements of Rolimeter showed excellent stability of the knee. The mean IKDC score was 92.0 +/- 4.9 and the mean Lysholm score was 91.0 +/- 3.7, which all improved compared to preoperative scores. CONCLUSION: Arthroscopic reconstruction of anterior cruciate ligament with preservation of the remnant bundle has satisfactory effects on the knee stability, which could increase the angiogenesis and collagen of the ACL and improve the proprioception of the knee.

[Anterior cruciate ligament reconstruction with tendon graft enveloped by preserved remnants].

OBJECTIVE: To explore the curative effect of anterior cruciate ligament (ACL) reconstruction with tendon graft enveloped by preserved remnants. METHODS: From June 2009 to June 2011,76 patients with ACL injury were treated, and the ACL was reconstructed with tendon graft enveloped by preserved remnants. There were 59 males and 17 females, aged 15 to 46 years with an average of 29 years. The causes of injuries included sports in 32 cases, training in 20 cases, traffic accidents in 16 cases, and other reasons in 8 cases. The average disease duration was 3 weeks (2 to 5 weeks). The results of Lachman test was positive in 72 cases and anterior drawer test were positive in 76 cases. The preoperative IKDC score was 45.9 +/- 3.6. The preoperative Lysholm knee score was 54.3 +/- 4.5. RESULTS: All incisions got an one stage healing, and no early complications occurred. Sixty-nine cases were followed up, and the duration ranged from 17 to 31 months (mean, 23 months). The result of Lachman test was negative at the latest follow-up. At the latest follow-up, the degree of IKDC was A in 36 cases, B in 30 cases, C in 3 cases, no one in degree D. The postoperative IKDC score was 91.5 +/- 3.4, showing significant difference compared with preoperative score. The postoperative Lysholm score was 92.4 +/- 3.8, showing a significant difference compared with preoperative score. CONCLUSION: The clinical effect of anterior cruciate ligament (ACL) reconstruction with tendon graft enveloped by preserved remnants is satisfactory.

[Arthroscopic treatment of painful heel syndrome with radio-frequency].

OBJECTIVE: To evaluate therapy effect of radiofrequency in the treatment of painful heel syndrome under arthroscopy. METHODS: From January 2006 to December 2011, 13 patients with painful heel syndrome being admitted into our hospital were studied. There were 5 males and 8 femals, ranging in age from 35 to 68 years. All these surgeries were performed under local anesthesia. After constructing a man-made lacouna in the subcutaneous tissue above plantar fascia, a medial and a lateral portal were established on both sides of plantar fascia and at the anterior edge of calcaneal tuberosity. Hyperplasia and torn fiber tissue of plantar fascia, and plantar calcaneal bursa were removed with radiofrequency probe under arthroscopy. Then penetration of the plantar fascia was carried out in a reticulation-shaped pattern with a special radiofrequency probe TOPAZ. Each patient was assessed with VAS pain evaluation criteria and AOFAS ankle-hindfoot score system (AOFAS-AH) before and after operation. All the patients were followed up, and the duration ranged from 6 to 12 months. RESULTS: All the 13 patients got excellent recovery with their heel pain relieved significantly. VAS score was 8.71 +/- 1.64 before operation, 6.27 +/- 2.53 at the 1st month after operation, and 2.30 +/- 2.69 at the 6th month after operation. AOFAS-AH score was 56.43 +/- 3.72 preoperation, 68.15 +/- 7.38 at 1st month post operation, and 84.51 +/- 2.93 at 6th month after operation. There were no perioperative and postoperative complications related to the procedure, such as blood vessel and nerve injury, and infection. CONCLUSION: Plantar fasciitis and plantar calcaneal bursitis are main factors of painful heel syndrome. Due to advantages of being easy to operate, having definite effect and no use to do spur removal or plantar fasciotomy. Endoscopy assisted plantar calcaneal bursa removal and plantar fascia penetration by radiofrequency technique can be a satisfactory treatment method for painful heel syndrome.

A novel approach of prophylaxis to HBV recurrence after liver transplantation.

Liver transplantation (LT) in patients with hepatitis B virus (HBV) infection is associated with a high rate of graft loss and poor survival, unless re-infection can be prevented. Human hepatitis B immune globulin (HBIG) and nucleoside analogues (NA) have long been utilized to prevent re-infection. Previously, we generated a human monoclonal antibody (mAb), HB that recognizes the surface antigen of hepatitis B virus (HBV). We have constructed a secreted version of HB and cloned its genes into recombinant adeno-associated virus (AAV). We compared the efficiency of AAV vector after a single injection via intramuscular or intravenous routes without additional intervention. Then, we evaluated the activity of antibody HB in tree shrews treated with rAAV-HB and in vitro experiments. So, intramuscular injection of rAAV-HB was a suitable method for the immunoprophylaxis of HBV infection. This human antibody will be useful for the immunoprophylaxis of HBV infection.

[Biological effects of chlorogenic acid and body health].

Chlorogenic acid, as a phenolic acid, occurs ubiquitously in food. Proved to have a series of biological effects in vitro and in vivo, such as antioxidant capacity, radical scavenging activity, antimutagenic/anticarcinogenic effect, inflammation inhibiting and endothelial protective properties, etc., chlorogenic acid might therefore contribute to body health promotion to some extent, and be hopeful to provide new ways for chronic disease prevention. It's physicochemical properties, food distribution, metabolism information and biological effects are reviewed in this article.