Clinical Reasoning: A 60-Year-Old Man With Asymmetric Weakness and Persistent Fever.

Peripheral neuropathies, especially those with atypical features, remain a diagnostic challenge. In this case, a 60-year-old patient presented with acute-onset weakness starting in the right hand then sequentially involving the left leg, left hand, and right leg over 5 days. The asymmetric weakness was accompanied by persistent fever and elevated inflammatory markers. Subsequent development of rashes combined with careful review of the history led us to the final diagnosis and targeted treatment. This case highlights clinical pattern recognition with the help of electrophysiologic studies in peripheral neuropathies, which provide shortcuts to narrow the differential diagnosis. We also illustrate the important pitfalls from history taking to ancillary testing in diagnosing the rare but treatable cause of peripheral neuropathy (eFigure 1, links.lww.com/WNL/C541).

Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses.

It is well established that embryonic chromosomal abnormalities (both in the number of chromosomes and the structure) account for 50% of early pregnancy losses. However, little is known regarding the potential differences in the incidence and distribution of chromosomal abnormalities between patients with sporadic abortion (SA) and recurrent pregnancy loss (RPL), let alone the role of submicroscopic copy-number variations (CNVs) in these cases. The aim of the present study was to systematically evaluate the role of embryonic chromosomal abnormalities and CNVs in the etiology of RPL compared with SA. Over a 3-year period, 1556 fresh products of conception (POCs) from miscarriage specimens were investigated using single nucleotide polymorphism array (SNP-array) and CNV sequencing (CNV-seq) in this study, along with further functional enrichment analysis. Chromosomal abnormalities were identified in 57.52% (895/1556) of all cases. Comparisons of the incidence and distributions of chromosomal abnormalities within the SA group and RPL group and within the different age groups were performed. Moreover, 346 CNVs in 173 cases were identified, including 272 duplications, 2 deletions and 72 duplications along with deletions. Duplications in 16q24.3 and 16p13.3 were significantly more frequent in RPL cases, and thereby considered to be associated with RPL. There were 213 genes and 131 signaling pathways identified as potential RPL candidate genes and signaling pathways, respectively, which were centered primarily on six functional categories. The results of the present study may improve our understanding of the etiologies of RPL and assist in the establishment of a population-based diagnostic panel of genetic markers for screening RPL amongst Chinese women.

Giant Cell Tumor of Tendon Sheath with Tarsal Bones and Intertarsal Joint Invasion: A Case Report.

The giant cell tumor of tendon sheath (GCTTS) is a benign lesion most commonly attached to the tendons and bones of the fingers, hands, and wrists. The involvement of GCTTS to the foot is uncommon. The GCTTS invading tarsal bones and intertarsal joints is not described yet, and the appropriate diagnosis and treatment remain unclear. We report a case of GCTTS with the involvement of tarsal bones and intertarsal joint. Computed tomography scan and magnetic resonance imaging were used to further diagnose and evaluate the quality and range of tumor. The patient was treated with surgical excision of the tumor without application of bone graft. After adequate clearance of the tumor, the patient returned to an asymptomatic walk in 3 months. No malfunction, fracture, or tumor recurrence was found in 2-years follow-up. This report includes clinical, radiologic, histologic diagnostic, and surgical challenges in an unexpected lesion and a review of the literature.

Hounsfield Unit Values in ACR TI-RADS 4-5 Thyroid Nodules with Coarse Calcifications: An Important Imaging Feature Helpful for Diagnosis.

PURPOSE: The purpose of this study is to investigate the diagnostic role of Hounsfield unit (HU) values on noncontrast computed tomography (CT) for differentiating benignity from malignancy in the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) 4-5 nodules with coarse calcifications. PATIENTS AND METHODS: CT images of 216 ACR TI-RADS 4-5 nodules with coarse calcifications from 207 patients who underwent surgery in our hospital between 2017 and 2019 were retrospectively reviewed. The average HU values (AHUVs) and maximum HU values (MHUVs) of the nodules were measured on noncontrast CT. The distribution of AHUVs and MHUVs in benign and malignant nodules with coarse calcifications was analyzed using the Mann-Whitney test. Receiver operating characteristic (ROC) curves were used to identify the best cut-off values. Diagnostic performances were assessed according to the area under the ROC curve (AUC), sensitivity and specificity. RESULTS: Of the 216 ACR TI-RADS 4-5 nodules with coarse calcifications, 170 were benign and 46 were malignant. The AHUVs of benign and malignant nodules were 791 HU [interquartile range (IQR), 543-1025 HU] and 486 HU (IQR, 406-670 HU), respectively (P < 0.001). The MHUVs of benign and malignant nodules were 1084 HU (IQR, 717-1477 HU) and 677 HU (IQR, 441-986 HU), respectively (P < 0.001). The AUCs for AHUVs and MHUVs for predicting benign nodules with coarse calcifications were 0.759 and 0.732, and the cut-off values were 627.5 HU and 806.0 HU, with sensitivities of 67.6% and 68.8% and specificities of 73.9% and 67.4%, respectively. The sensitivity and specificity of the combination were 68.8% and 76.1%. CONCLUSION: AHUVs and MHUVs were helpful in differentiating benignity from malignancy in ACR TI-RADS 4-5 nodules with coarse calcifications. This may provide an important basis for reducing misdiagnosis and unnecessary aspiration or surgical trauma.

[Effects of VEGF-Notch Signaling Pathway on Proliferation and Apoptosis of Bone Marrow MSC in Patients with Aplastic Anemia].

OBJECTIVE: To evaluate the regulation of VEGF-Notch signaling pathway on proliferation and apoptosis of mesenchymal stem cells (MSC) in the patients with aplastic anemia (AA). METHODS: The bone marrow specimens of AA patients were collected for isolation and identification of BM MSC. Westen blot was used to detect the expression of VEGF-Notch signaling pathway-related proteins (VEGF, VEGFR, Notch 1, Jagged 1, Delta-like 1 and Hes1). The VEGF (100 ng/ml) and DAPT (γ-secretase inhibitor, 10 µmol/L) were respectively added into MSC culture system in oder to activate and inhibit the signaling transduction of VEGF-Notch in BM MSC. The proliferation, apoptosis and cell cycle of MSC in AA patients were detected by CCK8 assay and flow cyfometry. The adipogenic differentiation of BM MSC was detected by oil red O staining. RESULTS: The VEGF-Notch signaling pathway was significantly inhibited in AA BM tissues and AA MSC (P＜0.05) detected by Western blot. The intervention of VEGF and DAPT significantly activated and inhibited VEGF-Notch signaling in AA MSC, respectively. CCK8 assay showed that VEGF intervention significantly promoted the proliferation of MSC in AA patients (P＜0.05). Flow cytometry showed that VEGF significantly inhibited apoptosis of MSCs by blocking S phase cells (P＜0.05). CONCLUSION: The activation of VEGF-Notch can restore the proliferation function of MSC in AA patients.

Diagnostic value of computed tomography (CT) histogram analysis in thyroid benign solitary coarse calcification nodules.

This study was to investigate the diagnostic value of the computed tomography (CT) histogram in thyroid benign solitary coarse calcification nodules (BSCNs). A total of 89 thyroid solitary coarse calcification nodules (coarse calcification ≥5 mm, no definite soft tissue around calcification) confirmed either by surgery or histopathological examination in 86 cases enrolled from January 2009 to December 2015 were evaluated. These included 56 BSCNs and 33 malignant solitary coarse calcification nodules (MSCNs). Overall, 27 cut-off values were calculated by N (4≤N≤30) times of 50 Hounsfield units (HU) in the range of 200 to 1500 HU, and each cut-off value and the differences in the corresponding area percentages in the CT histogram were recorded for BSCN and MSCN. The optimal cut-off value and the corresponding area percentage were established by receiver operating characteristic (ROC) curve analysis. In the 19 groups with an ROC area under curve (AUC) of more than 0.7, at a cut-off value of 800 HU and at an area percentage of no more than 93.8%, the ROC AUC reached the maximum of 0.79, and the accuracy, sensitivity, and specificity were 75.3%, 80.4%, and 66.7%, respectively. At a cut-off value of 1050 HU and at an area percentage of no more than 93.6%, the accuracy, sensitivity, and specificity were 71.9%, 60.7%, and 90.9%, respectively. At a cut-off of 1150 HU and area of no more than 98.4%, the accuracy, sensitivity, and specificity were 70.8%, 57.1%, and 93.9%, respectively. At a cut-off of 600 HU and area of no more than 12.1%, the accuracy, sensitivity, and specificity were 61.8%, 39.3%, and 100.0%, respectively. Compared with the cut-off value of 800 HU and an area percentage of no more than 93.8%, the sensitivity of cut-off values and minimum areas of 1050 HU and 93.6%, of 1150 HU and 98.4%, and of 600 HU and 12.1%, was gradually decreasing; however, their specificity was gradually increasing. This can provide an important basis for reducing the misdiagnosis and unnecessary surgical trauma.

Effect of Chinese medicine treatment based on pattern identification on cellular immunophenotype of myelodysplastic syndrome.

OBJECTIVE: To observe the influence of treatment based on Chinese medicine pattern identification on cellular immunophenotype of the myelodysplastic syndrome (MDS). METHODS: Sixty patients with MDS were randomly and equally assigned to the treatment group and the control group using a randomized digital table. Thirty patients in each group included 3 risk levels (low, moderate and high risks) with each level 10 patients according to the international prognostic scoring system. The control group was given conventional therapy which was also used in the treatment group. While the treatment group was given Zuogui Pill () and Yougui Pill () for low risk patients; Qingwen Baidu Decoction () and Bazhen Decoction () for moderate risk patients; Gexia Zhuyu Decoction () and Qinghao Biejia Decoction () combined with Shiquan Dabu Decoction () for high risk patients. After the treatment, the differences of overall response rate and immunophenotype (CD13, CD14, CD15, CD33 and CD34) of each group were analyzed. RESULTS: The overall response rate of the treatment group was significantly higher than the control group in low risk and moderate risk patients (P=0.029), there was no statistical differences of overall response rate between the treatment group and the control group in high risk patients (P=0.089). The expressions of CD13, CD14, CD33 and CD34 in all three risk levels of the treatment group were obviously decreased after the treatment, while CD15 in all three risk levels of the treatment group was obviously increased after the treatment (P<0.05 or P<0.01). Meanwhile, the difference values of CD13 and CD33 in low risk level of the treatment group, CD33 and CD34 in moderate risk level of the treatment group as well as CD34 and CD15 in high risk level of the treatment group, were all greater than the control groups and they were statistically significant (P<0.05 or P<0.01). CONCLUSIONS: It shows a better therapeutic effect if the MDS patients treated with Chinese medicine pattern identification in addition to conventional therapy. Since the treatment may inhibit the malignant clones and improve the dysmaturity of granulocyte differentiation, it is a feasible option in clinical practice.

Negative methylation status of vimentin predicts improved prognosis in pancreatic carcinoma.

AIM: To determine the existence of a potential relationship between the methylation state of the Vimentin gene and its prognostic value in pancreatic cancer. METHODS: Sixty-four primary tumor specimens and normal tissues were collected consecutively from pancreatic cancer patients during surgery at Hangzhou First People's Hospital and Affiliated Hospital of the Logistics University of the Chinese People's Armed Police Force. DNA was extracted from the samples and subsequently quantitative methylation-specific polymerase chain reaction was used to detect the Vimentin methylation status of the samples. All of the patients were followed up to December 2012. χ(2) test, Kaplan-Meier survival and Cox regression statistical models were used. RESULTS: Out of 64 pancreatic cancer tissues, 21 were marked as Vimentin methylation-positive, and 43 were marked as Vimentin methylation-negative. The location of pancreatic carcinoma was related to the Vimentin methylation state. The pathological T staging (P < 0.001), adjuvant chemotherapy (P = 0.003) and the Vimentin methylation state (P = 0.037) were independent prognostic factors. CONCLUSION: In our study, Vimentin methylation status can predict the prognosis of pancreatic cancer patients. However, additional experiments and clinical trials are needed to accurately validate this observation.

Comparing the effect of An's Shaobei Injection ([symbols; see text]) with Xiaozhiling Injection ([symbols; see text]) in patients with internal hemorrhoids of grade I-III: a prospective cohort study.

OBJECTIVE: To compare the effect of An's Shaobei Injection ([symbols; see text]) with Xiaozhiling Injection ([symbols; see text]) in patients with internal hemorrhoids of grade I-III. METHODS: This cohort study included 1,520 internal hemorrhoids patients with grade I-III who were scheduled for liquid injection treatment from July 2003 to July 2009. The cohort included patients who underwent either An's Shaobei Injection treatment (the treatment group, 760 cases) or Xiaozhiling Injection treatment (the control group, 760 cases). All patients were followed up regularly for 3 years; the observing indices included anal function recovery and clinical response after operation. RESULTS: Among the 1,520 patients, 1,508 (99.2%) completed the 3-year follow-up. The efficacy rate was 97.5% in the treatment group, significantly higher than the control group (91.8%, P<0.01). The recurrence rate in the treatment group was 0.5%, significantly lower than that of the control group (1.3%, P<0.01). In addition, perianal callosity occurred in 8 cases (1.1%) and anorectal stricture in 26 cases (3.5%) after operation in the control group. There was no perianal callosity and anorectal stricture in the treatment group. CONCLUSION: The treatment with An's Shaobei Injection demonstrated superior clinical effect to Xiaozhiling Injection with fewer adverse effects.

Synovial sarcoma of the neck masquerading as a malignant second branchial cleft cyst.

Synovial sarcoma is an uncommon, aggressive malignant tumor of the soft tissues primarily involving the extremities of young adults. Head and neck synovial sarcoma is rare, and its diagnosis and therapy are still challenging.We report a case of a young patient with synovial sarcoma, clinically masquerading as cystic mass of the neck and malignant second branchial cleft cyst. The pathological diagnosis of the sarcoma was confirmed by a multimodality diagnostic protocol, including histological, immunohistochemical and molecular genetic analysis. The patient underwent complete surgical excision followed by postoperative radiotherapy and recovered well.

Studies on the rice LEAF INCLINATION1 (LC1), an IAA-amido synthetase, reveal the effects of auxin in leaf inclination control.

The angle of rice leaf inclination is an important agronomic trait and closely related to the yields and architecture of crops. Although few mutants with altered leaf angles have been reported, the molecular mechanism remains to be elucidated, especially whether hormones are involved in this process. Through genetic screening, a rice gain-of-function mutant leaf inclination1, lc1-D, was identified from the Shanghai T-DNA Insertion Population (SHIP). Phenotypic analysis confirmed the exaggerated leaf angles of lc1-D due to the stimulated cell elongation at the lamina joint. LC1 is transcribed in various tissues and encodes OsGH3-1, an indole-3-acetic acid (IAA) amido synthetase, whose homolog of Arabidopsis functions in maintaining the auxin homeostasis by conjugating excess IAA to various amino acids. Indeed, recombinant LC1 can catalyze the conjugation of IAA to Ala, Asp, and Asn in vitro, which is consistent with the decreased free IAA amount in lc1-D mutant. lc1-D is insensitive to IAA and hypersensitive to exogenous BR, in agreement with the microarray analysis that reveals the altered transcriptions of genes involved in auxin signaling and BR biosynthesis. These results indicate the crucial roles of auxin homeostasis in the leaf inclination control.

Semi-rolled leaf1 encodes a putative glycosylphosphatidylinositol-anchored protein and modulates rice leaf rolling by regulating the formation of bulliform cells.

Leaf rolling is an important agronomic trait in rice (Oryza sativa) breeding and moderate leaf rolling maintains the erectness of leaves and minimizes shadowing between leaves, leading to improved photosynthetic efficiency and grain yields. Although a few rolled-leaf mutants have been identified and some genes controlling leaf rolling have been isolated, the molecular mechanisms of leaf rolling still need to be elucidated. Here we report the isolation and characterization of SEMI-ROLLED LEAF1 (SRL1), a gene involved in the regulation of leaf rolling. Mutants srl1-1 (point mutation) and srl1-2 (transferred DNA insertion) exhibit adaxially rolled leaves due to the increased numbers of bulliform cells at the adaxial cell layers, which could be rescued by complementary expression of SRL1. SRL1 is expressed in various tissues and is expressed at low levels in bulliform cells. SRL1 protein is located at the plasma membrane and predicted to be a putative glycosylphosphatidylinositol-anchored protein. Moreover, analysis of the gene expression profile of cells that will become epidermal cells in wild type but probably bulliform cells in srl1-1 by laser-captured microdissection revealed that the expression of genes encoding vacuolar H(+)-ATPase (subunits A, B, C, and D) and H(+)-pyrophosphatase, which are increased during the formation of bulliform cells, were up-regulated in srl1-1. These results provide the transcript profile of rice leaf cells that will become bulliform cells and demonstrate that SRL1 regulates leaf rolling through inhibiting the formation of bulliform cells by negatively regulating the expression of genes encoding vacuolar H(+)-ATPase subunits and H(+)-pyrophosphatase, which will help to understand the mechanism regulating leaf rolling.

[Expression of BRAF V600E mutation in different thyroid lesions].

OBJECTIVE: To evaluate the expression of BRAF V600E mutation in 240 Chinese patients with thyroid lesions. METHODS: Two hundred and forty Chinese patients with thyroid lesions, including 129 papillary thyroid carcinomas (PTC), 12 follicular carcinomas, 4 medullary carcinomas, 30 adenomas, 30 nodular goiters, and 35 papillary hyperplasia. DNA was extracted from thyroid biopsy and paraffin embedded thyroid tissues, and the expression of BRAF V600E mutation was detected by polymerase chain reaction and DNA sequencing assays. RESULTS: The presence of BRAF V600E mutation was found in 61 of the total group of 240 cases (25.4%). It was only detected in PTC (47.3%), and not detected in other types of malignant and benign thyroid lesions. There was a statistically significant difference between the expression of BRAF V600E mutation in classic type PTC (49.6%) and in follicular type PTC (12.5%,P < 0.05), but statistical data did not show any correlation between BRAF V600E mutation and clinicopathologic parameters in PTC (P > 0.05). CONCLUSIONS: BRAF V600E mutation has a significant correlation with PTC and the detection of BRAF V600E mutation may be used as an important prognostic marker of PTC. Our new method of DNA extraction from paraffin embedded tissues is efficient and inexpensive.

Hepatic angiomyolipoma: dynamic computed tomography features and clinical correlation.

AIM: To study the dynamic computed tomography (CT) features of hepatic angiomyolipoma (AML) in patients with or without tuberous sclerosis complex (TSC). METHODS: The clinical information, CT findings and histopathological results of hepatic AML were analyzed retrospectively in 10 patients. RESULTS: Hepatic AML was prone to occur in female patients (7/10), and most of the patients (8/10) had no specific symptoms. All tumors presented as well-defined, unenveloped nodules in the liver. Six patients with sporadic hepatic AML had a solitary hepatic nodule with a definite fat component. Non-fat components of the hepatic lesions were enhanced earlier and persistently. Prominent central vessels were noted in the portal venous phase in three patients. In four patients with hepatic AML and TSC, most of the nodules were within the peripheral liver. Seven fat-deficient nodules were found with earlier contrast enhancement and rapid contrast material washout in two patients. Lymphangioleiomyomatosis was found in one patient. CONCLUSION: Imaging features of hepatic AML are characteristic. Correct diagnosis preoperatively can be made in combination with clinical features.

Coincidence of hepatocelluar carcinoma and hepatic angiomyolipomas in tuberous sclerosis complex: a case report.

Tuberous sclerosis complex (TSC) is a dominantly inherited disorder which characterized by the growth of harmatomatous in multiple organs. Unlike the common development of renal angiomyolipoma, hepatic angiomyolipoma rarely occur in patients with TSC. We report here a patient with hepatic angiomyolipomas and concurrent hepatocellular carcinoma in TSC. This represents the first reported case in English literature. In this patient, multiple hepatic angiomyolipomas were diagnosed with recognition of their fat components and typical clinical settings. Hepatocellular carcinoma in the left liver lobe was definitely diagnosed by US guided biopsy. In such clinical settings, fat containing lesions in liver can be reasonably treated as angiomyolipomas, but non fat containing lesions must be differentiated from hepatocellular carcinoma, imaging guided biopsy can be adopted to confirm the diagnosis.