The small-molecule drug homoharringtonine targets HSF1 to suppress pancreatic cancer progression.

Heat shock factor 1 (HSF1), an essential transcription factor for stress response, is exploited by various tumors to facilitate their initiation, progression, invasion, and migration. Amplification of HSF1 is widely regarded as an indicator in predicting cancer severity, the likelihood of treatment failure and reduced patient survival. Notably, HSF1 is markedly amplified in 40% of pancreatic cancer (PC), which typically have limited treatment options. HSF1 has been proven to be a promising therapeutic target for multiple cancers. However, a direct small molecule HSF1 inhibitor with sufficient bioactivity and reliable safety has not been developed clinically. In this study, we successfully established a high-throughput screening system utilizing luciferase reporter assay specifically designed for HSF1, which leads to the discovery of a potent small molecule inhibitor targeting HSF1. Homoharringtonine (HHT) selectively inhibited PC cell viability with high HSF1 expression and induced a markedly stronger tumor regression effect in the subcutaneous xenograft model than the comparator drug KRIBB11, known for its direct action on HSF1. Moreover, HHT shows promise in countering the resistance encountered with HSP90 inhibitors, which have been observed to increase heat shock response intensity in clinical trials. Mechanistically, HHT directly bound to HSF1, suppressing its expression and thereby inhibiting transcription of HSF1 target genes. In conclusion, our work presents a preclinical discovery and validation for HHT as a HSF1 inhibitor for PC treatment.

Zero-Shot Neural Architecture Search: Challenges, Solutions, and Opportunities.

Recently, zero-shot (or training-free) Neural Architecture Search (NAS) approaches have been proposed to liberate NAS from the expensive training process. The key idea behind zero-shot NAS approaches is to design proxies that can predict the accuracy of some given networks without training the network parameters. The proxies proposed so far are usually inspired by recent progress in theoretical understanding of deep learning and have shown great potential on several datasets and NAS benchmarks. This paper aims to comprehensively review and compare the state-of-the-art (SOTA) zero-shot NAS approaches, with an emphasis on their hardware awareness. To this end, we first review the mainstream zero-shot proxies and discuss their theoretical underpinnings. We then compare these zero-shot proxies through large-scale experiments and demonstrate their effectiveness in both hardware-aware and hardware-oblivious NAS scenarios. Finally, we point out several promising ideas to design better proxies. Our source code and the list of related papers are available on https://github.com/SLDGroup/survey-zero-shot-nas.

Factors influencing postoperative visual improvement in 208 patients with tuberculum sellae meningiomas.

OBJECTIVE: Tuberculum sellae meningiomas (TSMs) usually compress the optic nerve and optic chiasma, thus affecting vision. Surgery is an effective means to remove tumors and improve visual outcomes. On a larger scale, this study attempted to further explore and confirm the factors related to postoperative visual outcomes to guide the treatment of TSMs. METHODS: Data were obtained from 208 patients with TSMs who underwent surgery at our institution between January 2010 and August 2022. Demographics, ophthalmologic examination results, imaging data, extent of resection, radiotherapy status, and surgical approaches were included in the analysis. Univariate and multivariate logistic regressions were used to assess the factors that could lead to favorable visual outcomes. RESULTS: The median follow-up duration was 63 months, and gross total resection (GTR) was achieved in 174 (83.7%) patients. According to our multivariate logistic regression analysis, age < 60 years (odds ratio [OR] = 0.310; P = 0.007), duration of preoperative visual symptoms (DPVS) < 10 months (OR = 0.495; P = 0.039), tumor size ≤ 27 mm (OR = 0.337; P = 0.002), GTR (OR = 3.834; P = 0.006), and a tumor vertical-to-horizontal dimensional ratio < 1 (OR = 2.593; P = 0.006) were found to be significant independent predictors of favorable visual outcomes. CONCLUSION: Age, DPVS, tumor size, GTR, and the tumor vertical-to-horizontal dimensional ratio were found to be powerful predictors of favorable visual outcomes. This study may help guide decisions regarding the treatment of TSMs.

Predictors and outcomes of withholding and withdrawal of life-sustaining treatments in intensive care units in Singapore: a multicentre observational study.

BACKGROUND: Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches. METHODS: This was a multicentre observational study of patients admitted to 21 adult ICUs across 9 public hospitals in Singapore over an average of three months per year from 2014 to 2019. The primary outcome measures were withholding and withdrawal of LST (cardiopulmonary resuscitation, invasive mechanical ventilation, and vasopressors/inotropes). The secondary outcome measure was hospital mortality. Multivariable generalised mixed model analysis was used to identify independent predictors for withdrawal and withholding of LST and if LST limitation predicts hospital mortality. RESULTS: There were 8907 patients and 9723 admissions. Of the former, 80.8% had no limitation of LST, 13.0% had LST withheld, and 6.2% had LST withdrawn. Common independent predictors for withholding and withdrawal were increasing age, absence of chronic kidney dialysis, greater dependence in activities of daily living, cardiopulmonary resuscitation before ICU admission, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and higher level of care in the first 24 h of ICU admission. Additional predictors for withholding included being of Chinese race, the religions of Hinduism and Islam, malignancy, and chronic liver failure. The additional predictor for withdrawal was lower hospital paying class (with greater government subsidy for hospital bills). Hospital mortality in patients without LST limitation, with LST withholding, and with LST withdrawal was 10.6%, 82.1%, and 91.8%, respectively (p < 0.001). Withholding (odds ratio 13.822, 95% confidence interval 9.987-19.132) and withdrawal (odds ratio 38.319, 95% confidence interval 24.351-60.298) were both found to be independent predictors of hospital mortality on multivariable analysis. CONCLUSIONS: Differences in the independent predictors of withholding and withdrawal of LST exist. Even after accounting for baseline characteristics, both withholding and withdrawal of LST independently predict hospital mortality. Later mortality in patients who had LST withdrawn compared to withholding suggests that the decision to withdraw may be at the point when medical futility is recognised.

[An analysis of the wall width before and after root canal therapy in mandibular second molars with C-shaped canals].

PURPOSE: To measure the wall width in mandibular second molars with C-shaped canals before and after root canal therapy using cone-beam CT(CBCT). METHODS: A total of 55 mandibular second molars from 38 patients which met the criteria for inclusion at Nanjing Stomatological Hospital, Affiliated Stomatological Hospital of Medical School of Nanjing University from January 2020 to July 2021 were analyzed．From this sample, ten teeth had been treated, while another 45 of them not. CT images of the teeth were reestablished by Mimics software 20.0. Then we made a section every 1mm perpendicular to the long axis of the teeth from apex to pulp floor. The first slice from apex to pulp chamber was named the slice 1. Along the slice 1 to crown 1 mm was called slice 1, and so forth. The wall thickness at different locations of all the slices was measured. The data was entered into SPSS 20.0 software package for analysis. RESULTS: Regardless of whether the teeth were treated or not, both the mesial and distal canal walls' average width were thicker than 1mm in all slices. At the same time, the mesial and distal canal walls' width were thicker than the width of buccal and lingual canal walls in all the slices from C-shaped root canal, except slices which were near pulp chamber(P＜0.05). As for the C-shaped root canals without root canal therapy, the width of lingual wall in the slice 1 to 4, as well as apex third root, was thinner than 1 mm. The width of buccal canal wall was thicker than the width of lingual canal wall in all slices except slice 11 and 12. As for the C-shaped root canals with root canal therapy, the width of buccal canal wall in slice 1 to 5, equivalent of apex half root, and the width of lingual wall in the slice 1 to 7, amount to apex two-thirds of root, was thinner than 1 mm. The width of buccal canal wall was thicker than the width of lingual wall in all slices except slice 1 and 9. There was no significant difference between the distal canal walls' width of C-shaped canals with and without root canal therapy(P＞0.05) . There was significant difference between the buccal canal walls' width of C-shaped canals with and without root canal therapy, as same as the mesial canal walls' width and the width of lingual canal wall (P＜0.05). CONCLUSIONS: The lingual canal walls' width in apex third root of C-shaped root canal were thin before canal preparation. The buccal walls' width in apex half root and the lingual canal walls' in apex two-thirds of root of C-shaped root canal were thin after canal preparation.

Targeting of STAT5 using the small molecule topotecan hydrochloride suppresses acute myeloid leukemia progression.

Acute myeloid leukemia (AML) is a common type of acute leukemia in adults and relapse is one of the main reasons for treatment failure. FLT3­ITD mutations are associated with poor prognosis, short disease­free progression survival and high relapse rates in patients with AML. STAT5 is activated by FLT3­ITD and drives the pathogenesis of AML. STAT5 activation is usually a hallmark of hematologic malignancies and occurs in ~70% of patients with AML. Moreover, STAT5 is a key molecule which regulates hematopoiesis, and its high expression is closely associated with drug resistance, thus direct targeting of STAT5 for AML is of great clinical value. The present study introduces a new small­molecule inhibitor that targets STAT5, presenting a promising approach for AML therapy. A high throughput fluorescence polarization (FP) screening system for STAT5 was designed and established, and used to screen an existing compound library to obtain the highly active small molecule inhibitor, topotecan hydrochloride. Topotecan hydrochloride was demonstrated to be an effective inhibitor of STAT5 by molecular docking prediction and cellular thermal shift assay. Topotecan hydrochloride bound to STAT5, inhibiting its dimerization, phosphorylation and transcription of specific target genes. The compound exhibits cellular activity at the nanomolar level and significantly inhibits the proliferation of human AML cell lines and FLT3­ITD+ AML cells. Furthermore, topotecan hydrochloride has the potential to exert an anti­tumor effect in vivo. Overall, topotecan hydrochloride offers a new opportunity for the treatment of AML and other hematologic malignancies by directly targeting STAT5.

TET3-mediated DNA demethylation and chromatin remodeling regulate T-2 toxin-induced human CYP1A1 expression and cytotoxicity in HepG2 cells.

T-2 toxin is a hazardous environmental pollutant that poses a risk to both farm animals and humans. Our previous research has reported that T-2 toxin highly induced the expression of human cytochrome P450 1A1 (CYP1A1), which may be a representative inducible marker of T-2 toxin and mediate the toxicity of T-2 toxin. In this study, we found that T-2 toxin decreased the DNA methylation levels of the CpG islands on the CYP1A1 promoter by inducing the expression of eleven translocation family protein 3 (TET3) and facilitating its binding to the promoter. These DNA methylation changes then generated an activated chromatin structure on the CYP1A1 promoter by releasing the repressor complex methyl-binding protein 2 (MeCP2) and histone deacetylase 2 (HDAC2), increasing the active histone modification markers, including H3K4ac, H3K9ac and H3K14ac, and facilitating RNA pol II and NRF1/Sp1 recruitment, which ultimately led to the transcriptional activation of CYP1A1. Interestingly, TET3-mediated CYP1A1 induction enhanced the cytotoxicity of T-2 toxin through inhibiting cell proliferation. Our results demonstrate that T-2 toxin-induced CYP1A1 expression is detrimental to cells and clearly show how T-2 toxin inhibits cell proliferation through regulating CYP1A1 expression from an epigenetic perspective. The findings broaden our current knowledge of the epigenetic mechanisms regulating environmental factors-induced CYP1A1 expression and cytotoxicity. TET3 may serve as a potential new target for toxicogenic detoxification.

Investigation of cytochrome P450 inhibitory properties of deoxyshikonin, a bioactive compound from Lithospermum erythrorhizon Sieb. et Zucc.

Deoxyshikonin, a natural naphthoquinone compound extracted from Lithospermum erythrorhizon Sieb. et Zucc (Boraginaceae), has a wide range of pharmacological activities, including anti-tumor, anti-bacterial and wound healing effects. However, the inhibitory effect of deoxyshikonin on cytochrome P450 (CYP) remains unclear. This study investigated the potential inhibitory effects of deoxyshikonin on CYP1A2, 2B1/6, 2C9/11, 2D1/6, 2E1 and 3A2/4 enzymes in human and rat liver microsomes (HLMs and RLMs) by the cocktail approach in vitro. The single-point inactivation experiment showed that deoxyshikonin presented no time-dependent inhibition on CYP activities in HLMs and RLMs. Enzyme inhibition kinetics indicated that in HLMs, deoxyshikonin was not only a competitive inhibitor of CYP1A2 and 2E1, but also a mixed inhibitor of CYP2B6, 2C9, 2D6 and 3A4, with Ki of 2.21, 1.78, 1.68, 0.20, 4.08 and 0.44 µM, respectively. In RLMs, deoxyshikonin not only competitively inhibited CYP2B1 and 2E1, but also exhibited mixed inhibition on CYP1A2, 2C11, 2D1 and 3A2, with Ki values of no more than 18.66 µM. In conclusion, due to the low Ki values of deoxythiokonin on CYP enzymes in HLMs, this may lead to drug-drug interactions (DDI) and potential toxicity.

Incidence and survival of benign, borderline, and malignant meningioma patients in the United States from 2004 to 2018.

Meningioma is the most common primary central nervous system tumor, and its incidence is increasing. A systematic epidemiological and clinical analysis is required to better estimate its public health impact and understand its prognostic factors. Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2018 for all types of meningiomas without an age restriction. Age-adjusted incidence rates (IRs) and 95% confidence intervals were estimated according to sex, age, race, ethnicity, and tumor location. Kaplan-Meier analysis and multivariate Cox proportional hazard models were used to analyze the overall survival (OS). The competing risk regression model of Fine-Gray was used to analyze cause-specific survival. Data from a total of 109 660 meningioma patients were analyzed. A majority of patients were older than 60 years, and only 0.41% of patients were 0-19 years. The meningioma IRs were higher in females, Black, and non-Hispanic patients than in males, White, and Hispanic patients, respectively, and IRs increased with age. The ratio of IRs for females to males was 2.1 and also increased with age, peaking at 3.6 in the 45-49-year-old group. Older and male patients with all types of meningiomas, Black patients with benign and borderline meningiomas, and patients with larger borderline and malignant meningiomas showed poorer prognosis. For all meningioma types, surgical resection improved survival. The reported incidence rates and survival trends covered all demographics and subtypes of meningiomas. Older age, male sex, Black race, and tumor size may be important prognostic factors for meningioma cases, and tumor resection can substantially improve survival among meningioma patients.

Aggressive sebaceous carcinoma of the scalp: a case report and literature review.

Sebaceous carcinoma (SC) is an uncommon and potentially aggressive adnexal neoplasm. SC presents most often as a periocular tumor arising from the ocular adnexa with unclear pathogenesis. Aggressive SC of the scalp is extremely rare. Here, we describe a rare case of aggressive SC of the scalp in a 61-year-old female, who presented with a scalp neoplasm lasting for two months. Cranial magnetic resonance imaging (MRI) revealed a partly necrotic and cystic tumor with mixed signal shadow. The parietal multiple destructive lesions invaded the skull, involved the dura mater, and compressed the associated superior sagittal sinus. A wide local lesion excision with I stage repair of dura mater and I stage bone graft of skull was performed in our department. The patient was treated with external radiation to prevent recurrence and was followed for 3 years with favorable results. The relevant literature regarding aggressive SC was reviewed, and the clinical manifestations, radiological characteristics, surgical strategies, histopathological findings, and prognosis are discussed. This cutaneous malignancy invaded skull, dura mater or brain, or metastasized to the lymph nodes and viscera, with high recurrence and fatality rates. It is necessary to be aware of these rare examples which showed unexpectedly clinical behaviors. Early precise diagnosis and improved radical treatment remain essential steps against aggressive cutaneous malignancy. Patients with aggressive SC of the scalp should be closely followed to assess recurrence and distant metastasis.

Syringomyelia with left knee charcot arthropathy: a case report.

We describe a rare case of syringomyelia with left knee Charcot arthropathy in a 35-year-old male, who presented with dissociative sensory disorder, muscle atrophy, painless knee joint swelling and limited joint mobility. Early diagnosis and appropriate treatment are essential in avoiding disease progression.

[Reproductive characteristics and habitat factors of Acanthopanax giraldii].

The growth parameters,clonal propagation parameters and sexual reproduction parameters of Acanthopanax giraldii population were systematically investigated and analyzed by means of population ecology in this study. The correlation among the above mentioned parameters and the correlation among canopy density,topography and soil fertility factors were analyzed. It is clear that there was a significant correlation among the clonal ramets,the fruit production capacity of the cluster and the new shoot production capacity of the A. giraldii. Sexual reproduction and clonal reproduction played an important role in the continuation of the population. Illumination was the key ecological factor that determined growth type. The increase in canopy density changed the population from " group clonal growth" to " guerrilla clonal growth",and the higher stand closure degree and low-strength herb layer competition was a necessary condition for seed germination and colonization. Under the background of natural forest protection and sustainable development of resources,the reproductive characteristics of wild A. giraldii resulted in the decrease of its recoverable quantity.

Sellar chondrosarcoma presenting with amenorrhea: A case report.

RATIONALE: Intracranial chondrosarcomas are rare entities and most of which arise off the midline. Chondrosarcomas that occur in the sellar region are extremely rare, and to the best of our knowledge, there is no reporting about sellar chondrosarcoma with amenorrhea as the onset symptom. PATIENT CONCERNS: A 45-year-old woman presented with a 7-month history of amenorrhea and a 3-month history of progressive visual loss in the left eye. DIAGNOSIS: The patient was diagnosed with recurrent sellar chondrosarcoma arising from intrasellar with extensive tumor invasion into bilateral sphenoid sinuses. INTERVENTIONS: Twice endonasal transsphenoidal tumorectomies were performed followed with a stereotactic radiotherapy and hormone replacement therapy. OUTCOMES: The patient's condition was stable and her visual symptoms improved, the hormones returned to normal, and no recurrence was noted on MRI after six months. LESSONS: Sellar chondrosarcomas with the onset of endocrine dysfunctions are extremely rare, which may be misdiagnosed as pituitary adenoma and the definitive diagnosis depends on histopathological and immunohistochemical evidence. The first choice of treatment is surgery with the goal of complete resection, and postoperative adjuvant radiotherapy should be highlighted.

Alternative splicing of human telomerase reverse transcriptase in gliomas and its modulation mediated by CX-5461.

BACKGROUND: Glioma is a heterogeneous, invasive primary brain tumor with a wide range of patient survival and a lack of reliable prognostic biomarkers. Human telomerase reverse transcriptase (hTERT) has been reported in the presence of multiple transcripts in various tumor systems. The biological function and precise regulatory mechanisms of hTERT transcripts remain uncertain. METHODS: Alternative splicing of hTERT and telomerase activity were examined in 96 glioma specimens, including 38 glioblastomas (GBMs), 23 oligodendrogliomas (ODMs), and 35 oligoastrocytomas (OAMs). The correlation between telomerase activity or hTERT transcripts and patient clinical characteristics was investigated. We examined the regulation of alternative splicing of hTERT and telomerase activity by G-quadruplex stabilizer CX-5461 in GBM cells. The biological effects of CX-5461 on GBM cell lines, including inhibition of cell proliferation, effects on cell cycle/apoptosis, and telomere DNA damage were further explored. RESULTS: The ß splicing was verified in human gliomas and hTERT+ß was significantly correlated with higher telomerase activity, higher KPS, larger tumor size, and higher tumor grades. Meanwhile, glioma patients lacking hTERT+ß expression or telomerase activity showed a significant survival benefit. Notably, CX-5461 altered hTERT splicing patterns, leading to an increase of hTERT-ß transcript and a decrease of hTERT+ß transcript expression, which inhibits telomerase activity. In addition, CX-5461 had cytotoxic effects on GBM cells and caused telomere DNA damage response, induced G2/M arrest and apoptosis. CONCLUSIONS: The hTERT+ß is verified to be correlated with clinical parameters in gliomas, and could serve as a prognostic marker or possibly therapeutic target for gliomas. CX-5461 can regulate the splicing pattern of hTERT, inhibit telomerase activity, and kill GBM cells.

Oncosis-like cell death is induced by berberine through ERK1/2-mediated impairment of mitochondrial aerobic respiration in gliomas.

Gliomas, the most common primary malignant brain tumor, exhibit high metabolic activity. The targeting of metabolism alterations, particularly in mitochondria, is emerging as an efficient approach for curing cancers. Here, we showed that berberine, a natural compound that is used as an antibacterial agent, could reduce cellular viability and induce oncosis-like death, characterized by cell swelling, cytoplasmic vacuoles and plasma membrane blebbing, in gliomas, and that these effects were correlated with intracellular adenosine triphosphate (ATP) depletion. We also found that berberine induced autophagy as a protective effect and decreased the oxygen consumption rate (OCR), which could inhibit mitochondrial aerobic respiration by repressing phosphorylated extracellular regulated protein kinases (p-ERK1/2). Furthermore, the down-regulation of mitochondrial p-ERK1/2 by berberine inhibited aerobic respiration and led to glycolysis, an inefficient energy production pathway. In addition, berberine reduced tumor growth and inhibited Ki-67 and p-ERK1/2 expression in vivo. The results demonstrate that berberine, which represses aerobic oxidation in mitochondria and decreases their energy production efficiency, decreases metabolic activity by reducing ERK1/2 activity.

Xanthogranulomatous pituitary adenoma: A case report and literature review.

Xanthogranuloma, also referred to as cholesterol granuloma or xanthogranulomatous reaction, is a granulomatous lesion that is infrequently found in the sellar and parasellar regions. Xanthogranulomatous pituitary adenoma is relatively rare and, thus, the etiology, diagnosis, management and prognosis of this condition remain incompletely understood. We herein report the case of a 56-year-old female patient who presented to our institution with intermittent headache, vomiting and distending pain in the bilateral orbital regions. Brain magnetic resonance imaging revealed a sellar mass with a heterogeneous signal. The mass was subtotally resected, and histopathological examination confirmed the diagnosis of xanthogranulomatous pituitary adenoma. Although the patient's symptoms were relieved following surgical treatment, intractable hyponatremia and diabetes insipidus developed and she received hormone replacement therapy. At the last follow-up (November 2016), the patient remained recurrence-free. A total of 14 cases of pituitary adenoma with concomitant xanthogranuloma were identified in the literature, and the clinical and radiological manifestations are discussed. Sellar xanthogranuloma is usually associated with craniopharyngioma or Rathke's cleft cyst; however, it may also occur in isolation. Xanthogranulomatous pituitary adenomas are infrequent, making their diagnosis challenging. Surgical resection is the preferred treatment, and attention should be paid to postoperative hypopituitarism and development of diabetes insipidus.

Occurrence and incidence of 18 per- and polyfluoroalkyl compounds in edible oils commonly consumed in Guiyang, China.

A systematic examination was conducted for the first time of a wide carbon-chain range of per- and polyfluoroalkyl compounds (PFASs) in 83 samples of edible vegetable and animal oils from Guiyang, China. The occurrence and levels of 18 PFASs in seven types of edible oil were analysed. Analytes were determined based on a simplified, sensitive and reliable solvent extraction and liquid chromatography-tandem mass spectrometry method. Ten target PFASs were found and the most frequently detected compounds with maximum concentration were PFOS (88%, 1.93 ng g-1), PFNA (55.4%; 6.76 ng g-1), PFHxS (39.8%; 0.36 ng g-1), and PFOA (16.9%; 0.15 ng g-1), respectively. The total PFASs concentrations ranged from 0.02 to 6.76 ng g-1, with a mean of 0.94 ng g-1. Significant differences of occurrence between vegetable oils and animal oils were demonstrated based on comparative analysis of the existing data. The investigation results showed that the effect of production reductions of PFOS and PFOA by regulatory was also reflected in edible oils. The dietary intakes of PFOS and PFOA for adults were estimated, which were lower than the available tolerable daily intake (TDI). Because of the global lack of food regulatory thresholds for most per- or polyfluoroalkyl compounds, it was difficult to draw any conclusion at this stage as to how human health is affected through exposure to these compounds. The baseline information of this study will assist in guiding the direction for future investigations and monitoring studies on occurrence, fate and human health-effect research of PFASs.

Anatomic and Ultrasonic Study Based on Selective Tibial Neurotomy.

BACKGROUND: Selective tibial neurotomy (STN) was considered as an effective procedure for the treatment of spastic feet. It is also widely used for treating obese calves in some Asian countries. This study aimed to provide morphologic measurement data and theoretical support for the operation and intraoperative localization. METHODS: Fifty lower legs from 20 embalmed cadavers and 5 fresh corpses were dissected to observe and record the relationship of 4 branches of the tibial nerve, as well as the length, width, and thickness of the triceps surae. An ultrasonic transducer was also used to measure the thickness of muscles of 50 volunteers and acquire the ultrasonic image of muscles and nerve branches. RESULTS: Anatomic results showed that the tibial nerve gave off 4 branches in a proximal to distal direction: the medial sural cutaneous nerve, the motor branches innervating the medial and lateral gastrocnemius, and the motor branch innervating the soleus. These nerve branches had 8 patterns of origin. A significant finding was that the nerve innervating the soleus consisted of 2 branches. Ultrasonic measurement results showed that the thickness of the gastrocnemius and the soleus were positively related to the circumference of the calf. CONCLUSIONS: The calf circumference was positively related to the thickness of the soleus and the gastrocnemius. Diverging patterns of tibial nerve branches were multiple, and caution should be used to prevent damaging other branches. Tibial nerve, branches, and diverging sites could be seen clearly in the ultrasonic image. A preoperational ultrasonic examination is recommended.

Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies.

Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

SPOCK1 is upregulated in recurrent glioblastoma and contributes to metastasis and Temozolomide resistance.

OBJECTIVES: Glioblastoma multiforme (GBM) is the most aggressive brain tumour type in humans. Its poor prognosis is largely attributed to its invasiveness and high rate of recurrence. Recurring GBM is commonly resistant to chemotherapeutic drugs, making it specially difficult to treat. Recent studies have revealed that matricellular glycoprotein SPOCK1 to be upregulated in several cancer types and to be specifically expressed in invasive GBM, but not in other types of non-invasive brain tumour, which prompted us to study the mechanism of action of SPOCK1 in invasion, recurrence and drug resistance of GBM cells. MATERIALS AND METHODS: SPOCK1 expression in GBM tissues was evaluated using qPCR, Western blotting and immunohistochemical staining. Cell migration was tested by the wound healing method and cell invasion was assessed using transwell plates with Matrigel coating. Western blotting was performed for E-cadherin, vimentin, N-cadherin, p-Akt and Akt. Cell viability was examined using the MTT assay. RESULTS: We found that the expression of SPOCK1 was significantly upregulated in recurrent GBM. We also demonstrated that SPOCK1 positively regulated migration, invasion and EMT process of GBM cells. Furthermore, SPOCK1 mediated TMZ resistance in GBM, as knockdown of SPOCK1 expression in TMZ-resistant GBM cells substantially sensitized these cells to TMZ. CONCLUSION: SPOCK1 results were positive and it mediated TMZ resistance in GBM. In addition, SPOCK1 regulated invasion and TMZ resistance in GBM cells via the Akt signalling pathway.