EBV-positive small cell neuroendocrine carcinoma of nasopharynx as a probably unique subtype of neuroendocrine carcinoma: a clinicopathologic study of three cases and literature review.

BACKGROUND: There is currently scarcity of information on small cell neuroendocrine carcinoma of the nasopharynx (SCNEC-nasopharynx). It is believed that this type of cancer is not associated with Epstein-Barr virus (EBV) infection and is indistinguishable from classic SCNEC occurring in other organs. MATERIALS AND METHODS: Herein we provided 3 cases of nasopharyngeal mass in our hospital, two males and one female. On admission, these patients were considered nasopharyngeal carcinoma with lymph node metastasis, and one of them had liver metastasis. The nasopharyngeal mucosal tissues were biopsied for pathological examination including immunohistochemistry and in situ hybridization. PubMed database was searched for articles about SCNEC-nasopharynx published up to April 2024 in any language. RESULT: The 3 cases had similar histological features of SCNEC in other organs but differed in rich- tumor-infiltrating lymphocytes (TILs). All of them stained for pancytokeratin (panCK) and epidermal growth factor receptor (EGFR). Case 1 and Case 2 diffusely expressed insulinoma-associated protein 1(INSM-1) and synaptophysin (Syn), Case 3 strongly stained for CD56 and Syn. Immunostaining of all 3 cases for p40, p63, TTF-1, CK20, S-100 and NUT showed negative. BRG-1, INI-1 and Rb were retained. And p53 all showed wild-type expression. The Ki-67 labeling indiced of case 1, 2, and 3 were 80%, 90%, and 80%, respectively. In situ hybridization showed strong and uniform nuclear positivity of EBV-encoded small RNAs (EBER) in the neoplastic cells of 3 cases. CONCLUSION: EBV-positive SCNEC-nasopharynx was exactly rare. The origin of this tumor is still controversial. It may originate from EBV-infected mucosal epithelium like nasopharyngeal carcinoma. Based on our cases and relevant literature, we found EBV-positive SCNEC-nasopharynx as a probably site-specific subtype of SCNEC with differing pathogenetic mechanism. The subtype not only virus positivity but also that it was associated with TILs and did not show p53 or Rb alterations by immunohistochemistry. It may be more responsive to treatment and have a better prognosis than classic SCNEC. We will continue to follow-up these patients and collect additional cases to further understand the unique biology of this rare solid tumor.

CT-guided ozone-mediated lumbar-renal sympathetic denervation for resistant hypertension treatment: A pilot single-arm clinical trial.

BACKGROUND: Renal sympathetic denervation (RDN) reduces blood pressure (BP). METHODS: This single-arm open-label study enrolled patients with resistant hypertension (RH) and treat them by CT-guided ozone mediated lumbar-renal sympathetic denervation (L-RDN). The primary endpoint was to assess the changes of BP over 24-h ambulatory BP monitoring (ABPM) and to evaluate the anti-hypertensive medication burden (AHMB) at 3-month follow-up. This study was registered in Chictr.org.cn (ChiCTR2300071375). RESULTS: 17 patients (mean age 65.12 ± 10.77 years) with AHMB of 4.12 ± 1.11 were enrolled. After the procedure, 7 patients (46.7 %) matched the criteria for antihypertensive medication reduction. The AHMB decreased to 3.87 ± 0.96 for the whole objectives and from 3.87 ± 0.96 to 3.55 ± 0.78 for patients with normal baseline renal function. On top of the lessened AHMB, L-RDN further reduced morning systolic BP (SBP) by -8.6 ± 4.0 mmHg (p = 0.034) and diastolic BP (DBP) by -4.6 ± 2.1 mmHg (p = 0.032) for all participants and morning SBP by -13.2 ± 3.6 mmHg (p < 0.001), morning DBP by -6.2 ± 2.4 mmHg (p = 0.011) and daytime SBP by -4.1 ± 1.6 mmHg (p = 0.009) for those with normal baseline renal function at 3-month of follow-up. No adverse events were reported intra- and post operation. CONCLUSIONS: CT-guided ozone-mediated L-RDN might be an innovative approach of RDN for treating RH. Confirmatory studies are warranted.

Epithelioid Subtype Gastrointestinal Stromal Tumors of Stomach in an Endoscopic Biopsy: A Potential Diagnostic Pitfall.

Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract with a broad morphological spectrum. Although epithelioid GISTs account for 20% of GISTs, their morphological features may pose a diagnostic pitfall for pathologists due to their morphological similarities to poorly differentiated adenocarcinoma and lymphoma. Case Presentation: Herein, we report a 65-year-old male patient with gastric epithelioid GIST misdiagnosed as adenocarcinoma for four years. During this period, he was treated with chemotherapy combined with PD-L1 immunotherapy. The clinicians thought the treatments were effective. However, there was no significant change in tumor size. The patient's clinical symptoms did not improve significantly as well. Finally, an endoscopic biopsy was performed again and gastric epithelioid GIST was confirmed in our hospital through morphology, immunohistochemistry, and whole-genome sequencing. Conclusion: A broad morphological spectrum and diverse immunophenotypic changes of GISTs could represent a pitfall for pathologists. However, predisposed anatomical sites, morphology, and corresponding immunohistochemical markers are of great significance for the diagnosis of GISTs and the differential diagnosis from other diseases. On the other hand, clinicians should diagnose and comprehensively evaluate treatment effects based on the patient's clinical symptoms and relevant laboratory examinations, instead of over-reliance on pathological diagnosis.

An in situ thermal cross-linking binder for silicon-based lithium ion battery.

Silicon has been regarded as one of the most promising anode materials for lithium-ion batteries (LIBs) due to its highest specific capacity and low (de)lithiation potential, however, the development of practical applications for silicon are still hindered by devastating volume expansion and low conductance. Herein, we have proposed an in situ thermally cross-linked water-soluble PA@PAA binder for silicon-based LIBs to construct dynamic cross-linking network. Specifically, ester bonds between -P-OH in phytic acid (PA) and -COOH in PAA, which are generated by thermal coupling, are designed to synergize with hydrogen bonds between the PA@PAA binder and silicon particles to dissipate the high mechanical stresses, which is verified by theoretical calculation. GO is further adopted to protect silicon particles from immediate contact with electrolyte to improve initial coulombic efficiency (ICE). A range of heat treatment temperatures is explored to optimize the previous process conditions and the optimum electrochemical performance is provided by Si@PA@PAA-220 electrodes with high reversible specific capacity of 1322.1 mAh/g at a current density of 0.5A/g after 510 cycles. Characterization has also revealed that PA@PAA is involved in electrochemical process and tunes the ratio of organic (LixPFy/LixPOyFZ)-inorganic (LiF) to consolidate solid electrolyte interface (SEI) during cycles. In brief, this applicable fascial in situ strategy can effectively improve the stability of silicon anodes for high energy density lithium-ion batteries.

Rationally designed rGO@CNTs@CNFs film as self-supporting binder-free Si electrodes for high-performance lithium-ion batteries.

Si has become the most promising anode materials for lithium-ion batteries (LIBs) due to its high theoretical specific capacity and comparable low discharge potential. However, the practical usage of Si is still hindered by its huge volume expansion. To release volume stress and improve conductance, designed self-supporting binder-free Si electrode endowed with three-dimensional structure has been come up in this research. The pore structure is adjusted by rationally designing the proportion of carbon nanotubes (CNTs) and carbon nanofibers (CNFs) to alleviate volume change. Simultaneously, construct stable conductivity network was fabricated via ice crystal self-assemble freezing technique following compress and carbonization process. The electrochemical specific capacity of rGO@CNTs@CNFs@Si-2 electrode has stably remained at 2250 mAh/g after 100 cycles (100 mA/g) with benign rate capabilities. This simple self-assemble method for self-supporting binder-free Si electrode would open a new route to exploit high energy density Si-based electrode for flexible LIBs.

Intervertebral Foramen Injection of Ozone Relieves Mechanical Allodynia and Enhances Analgesic Effect of Gabapentin in Animal Model of Neuropathic Pain.

BACKGROUND: In a 5-year follow-up study in a hospital in southern China, it was shown that intervertebral foramen (IVF) injection of ozone at the involved segmental levels could significantly alleviate paroxysmal spontaneous pain and mechanical allodynia in patients with chronic, intractable postherpetic neuralgia (PHN) and improve the quality of life. However, so far no proof-of-concept studies in animals have been available. OBJECTIVE: This study was designed to investigate whether IVF ozone has an analgesic effect on animal models of neuropathic and inflammatory pain. STUDY DESIGN: Experimental trial in rats. SETTING: Institute for Biomedical Sciences of Pain. METHODS: By IVF injection, a volume of 50 µl containing 30 µg/mL ozone-oxygen mixture or 50 µl air was carried out on male Sprague-Dawley rats of naïve, inflammatory pain states produced by injections of either bee venom or complete Freud's adjuvant, and neuropathic pain state produced by spared nerve injury, respectively. The effects of IVF ozone on pain-related behaviors were evaluated for 2 weeks or one month. Then combined use of gabapentin (100 mg/1 kg body weight) with IVF ozone was evaluated in rats with neuropathic pain by intraperitoneal administration 5 days after the ozone treatment. Finally, the analgesic effects of another 4 drugs, AMD3100 (a CXCR4 antagonist), A-803467 (a selective Nav1.8 blocker), rapamycin (the mTOR inhibitor), and MGCD0103 (a selective histone deacetylase inhibitor) were evaluated for long term through IVF injection, respectively. RESULTS: (1) IVF injection of ozone at L4-5 was only effective in suppression of mechanical allodynia in rats with neuropathic pain but not with inflammatory pain; (2) the analgesic effects of IVF ozone lasted much longer (> 14 days) than other selective molecular target drugs (< 48 hours) inhibiting or antagonizing at Nav1.8 (A-803467), CXCR4 (AMD3100), mTOR (rapamycin), and histone deacetylase (MGCD0103); (3) combined use of systemic gabapentin and IVF ozone produced a synergistic analgesic effect in rats with neuropathic pain. LIMITATIONS: Evaluation of the possible analgesic effects of the intraplantar injection of ozone was not performed. CONCLUSIONS: In the present study, we provided a line of evidence for the first time that IVF injection of ozone selectively relieved neuropathic pain but not inflammatory pain, and enhanced the analgesic effect of gabapentin. KEY WORDS: Chronic pain, neuropathic pain, inflammatory pain, ozone therapy, interventional therapy, gabapentin, spared nerve injury, bee venom, complete Freud's adjuvant.

Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin.

Intractable central post-stroke pain (CPSP) is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and changes in mechanical or thermal pain sensitivity in a rat CPSP model with experimental thalamic hemorrhage produced by unilateral intra-thalamic collagenase IV (ITC) injection. Then, we evaluated the efficacy of gabapentin (GBP), an anticonvulsant that binds the voltage-gated Ca(2+) channel α2δ and a commonly used anti-neuropathic pain medication. Histological case-by-case analysis showed that only lesions confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of the thalamus and/or the posterior thalamic nucleus resulted in bilateral mechanical pain hypersensitivity. All of the animals displaying CPSP also had impaired motor coordination, while control rats with intra-thalamic saline developed no central pain or motor deficits. GBP had a dose-related anti-allodynic effect after a single administration (1, 10, or 100 mg/kg) on day 7 post-ITC, with significant effects lasting at least 5 h for the higher doses. However, repeated treatment, once a day for two weeks, resulted in complete loss of effectiveness (drug tolerance) at 10 mg/kg, while effectiveness remained at 100 mg/kg, although the time period of efficacious analgesia was reduced. In addition, GBP did not change the basal pain sensitivity and the motor impairment caused by the ITC lesion, suggesting selective action of GBP on the somatosensory system.

Linguistic adaptation, validation and comparison of 3 routinely used neuropathic pain questionnaires.

BACKGROUND: Neuropathic pain questionnaires are efficient diagnostic tools for neuropathic pain and play an important role in neuropathic pain epidemiologic studies in China. No comparison data was available in regards to the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), the Neuropathic Pain Questionnaire (NPQ) and ID Pain within and among the same population. OBJECTIVE: To achieve a linguistic adaptation, validation, and comparison of Chinese versions of the 3 neuropathic pain questionnaires (LANSS, NPQ and ID Pain). STUDY DESIGN: A nonrandomized, controlled, prospective, multicenter trial. SETTING: Ten pain centers in China. METHODS: Two forward translations followed by comparison and reconciliation of the translations. Comparison of the 2 backward translations with the original version was made to establish consistency and accuracy of the translations. Pilot testing and pain specialists' evaluations were also required. A total of 140 patients were enrolled in 10 centers throughout China: 70 neuropathic pain patients and 70 nociceptive pain patients. Reliability (Cronbach's alpha coefficients and Guttman split-half coefficients) and validity (sensitivity, specificity, positive and negative predictive values, receiver operating characteristic [ROC] curves and the area under the ROC curves) of the 3 questionnaires were determined. ROC curves and the area under the ROC curves of the 3 questionnaires were also compared. RESULTS: Chinese versions of LANSS, NPQ and ID Pain had a good reliability (Cronbach's alpha coefficients and Guttman split-half coefficients were greater than 0.7). Sensitivity, specificity, positive and negative predictive values of the Chinese versions of LANSS and ID Pain were considerably high ( > 80%). The area under the ROC curves of LANSS and ID Pain was significantly higher than that of NPQ (P < 0.05). There was no statistically significant difference between the area under the ROC curves of LANSS and ID Pain (P > 0.05). LIMITATION: The study was based on patients with a high school degree or above, which limited the application of the 3 neuropathic pain questionnaires to patients with lower educational levels. CONCLUSION: The Chinese versions of LANSS and ID Pain developed and validated by this study can be used as a diagnostic tool in differentiating neuropathic pain in patients whose native language is Chinese (Mandarin).