[Primary antibody deficiencies and respiratory manifestations in adults].

Primary antibody deficiencies (PAD) are a group of congenital disorders caused by genetic defects that affect the development and function of the body's immune defence mechanisms. Patients with PAD may present with recurrent infections, lymphoproliferation, autoimmune diseases, autoinflammation, or malignancies. Respiratory system manifestations may include bronchiectasis, bronchial asthma, and interstitial lung disease, among others. A comprehensive understanding of PADs will help to distinguish these covert cases from more common respiratory diseases.

[Efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage â ¡-â ¢ melanoma].

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.

Fermented rape pollen powder can alleviate benign prostatic hyperplasia in rats by reducing hormone content and changing gut microbiota.

Benign prostatic hyperplasia (BPH) can cause urethral compression, bladder stone formation, and renal function damage, which may endanger the life of patients. Therefore, we aimed to develop plant-based preparations for BPH treatment with no side effects. In this study, the Lactiplantibacillus plantarum 322Hp, Lactobacillus acidophilus 322Ha, and Limosilactobacillus reuteri 322Hr were used to ferment rape pollen. The fermented rape pollen was subsequently converted into fermented rape pollen powder (FRPP) through vacuum freeze-drying technology. After fermenting and drying, the bioactive substances and antioxidant capacity of FRPP were significantly higher than those of unfermented rapeseed pollen, and FRPP had a longer storage duration, which can be stored for over one year. To investigate the therapeutic effect of FRPP on BPH, a BPH rat model was established by hypodermic injection of testosterone propionate. The BPH rats were treated differently, with the model group receiving normal saline, the positive control group receiving finasteride, and the low, medium, and high dose FRPP group receiving FRPP at doses of 0.14 g/kg/d, 0.28 g/kg/d, and 0.56 g/kg/d, respectively. The results indicate that medium dose FRPP reduced the levels of hormone such as testosterone, dihydrotestosterone, and oestradiol in rats with BPH by about 32%, thus bringing the prostate tissue of BPH rats closer to normal. More importantly, medium dose FRPP treatment had a significant effect on the composition of gut microbiota in rats with BPH, increasing the levels of beneficial genera (such as Coprococcus and Jeotgalicoccus), and decreasing the levels of harmful pathogens (such as Turicibacter and Clostridiaceae_Clostridium) in the gut. This study showed that medium dose FRPP reduced the hormone level and regulated the unbalanced gut microbiota in BPH rats, thereby alleviating BPH.

[Analysis of the diagnosis and treatment of patients with SMARCB1 (INI-1)-deficient sinonasal carcinoma].

Objective: To summarize the clinical features, treatments and outcomes of patients with SMARCB1(INI-1)-deficient sinonasal carcinoma (SDSC). Methods: Fifteen patients who were diagnosed as SDSC in Beijing Tongren Hospital from October 2016 to June 2021 were retrieved, including nine males and six females, ranged from 25 to 78 years old. For TNM stage, one case was in stage T2, one case was in stage T3, 13 cases were in stage T4; 13 cases were in stage N0, two cases were in stage N2; 14 cases were in stage M0, one case was in stage M1. The most common paranasal sinus affected by tumor was the ethmoid sinus. Five patients were treated by radical surgical resection combined with postoperative adjuvant therapy, four patients treated by neoadjuvant therapy with surgical resection, three patients treated by surgical resection only, one patient treated by neoadjuvant therapy with concurrent chemoradiotherapy, one patient treated by preoperative radiotherapy with surgery, and one patient received palliative chemotherapy. Immunohistochemical analysis was performed in all cases. The Kaplan-Meier method was used to draw the survival curve, and the Log-rank test was used to compare the difference to 20 undifferentiated carcinoma patients with positive INI-1 expression in the same period. Results: Immunohistochemical analysis showed the complete absence of INI-1 expression in the tumor nuclei in all 15 cases. The follow-up information was available with a median follow-up time of 21 months (3-56 months). The 3-year overall survival rate, disease specific survival rate, disease-free survival rate and metastasis-free survival rate were 58.9%, 58.9%, 36.4% and 31.2%, respectively. Disease-free survival in SDSC patients was significantly lower compared with undifferentiated carcinoma patients with positive INI-1 expression (HR=2.87,95%CI:0.92~8.91,P=0.043). Cox regression analysis showed that patients with comprehensive treatment based on surgery had a better prognosis than others (HR=8.61,95%CI:1.38~53.73,P=0.021). Conclusion: SDSC is a highly aggressive malignant tumor with the characteristics of easy recurrence, early metastasis and poor prognosis. INI-1 immunohistochemical analysis is recommended in the pathologically poorly differentiated sinonasal carcinoma. Comprehensive treatment based on radical resection may be the first choice for SDSC patients.

[Clinical analysis of 61 cases of salivary duct carcinoma].

The clinical data of 61 patients of salivary duct carcinoma admitted to the First Medical Centre of Chinese PLA General Hospital from January 2010 to December 2020 were retrospectively reviewed. A total of 55 patients (90.2%) were male and 6 (9.8%) were female. There were 51 patients (83.6%) aged≥50 years. The primary tumor of 45 patients (73.8%) were from the parotid gland. There were 35 patients (57.4%) who had cervical lymph node metastasis and 25 patients (41.0%) had distant metastasis. All patients underwent surgery and 50 of them (82.0%) received adjuvant radiotherapy. The 3-year and 5-year survival rates were 58.0% and 43.3%, respectively. Compared with the patients who had undergone surgery only, the survival rates of those who had postoperative adjuvant radiotherapy and chemoradiotherapy were higher. It can be seen that radical surgical treatment is necessary, and postoperative radiotherapy can reduce the recurrence rate and increase the survival rate to a certain extent.

[Two families with Birt-Hogg-Dubé syndrome:case report and literature review].

Objective: To improve the awareness of Birt-Hogg-Dubé syndrome. Methods: We performed a retrospective analysis with two families of Birt-Hogg-Dubé syndrome (BHD syndrome) diagnosed in Department of Respiratory and Critical Care Medicine, Shenzhen People's Hospital from 2020 to 2021. Clinical manifestations, imaging features, diagnosis and gene detection results were summarized. Relative literatures were reviewed in Wanfang Database and PubMed from 2015 to 2021 by using the search terms of "BHD syndrome" "Birt-Hogg-Dubé" "Birt-Hogg-Dubé syndrome", respectively. Results: The probands of both families were female, aged 37 and 34 years respectively. The onset manifestation was pulmonary bullae combined with pneumothorax. Chest computed tomography (CT) imaging showed multiple pulmonary cysts in both lobes, and no skin lesions or renal tumors were found in either case. History of pneumothorax was present in Family 1 while absent in Family 2. The FLCN gene of the two probands and their relatives showed the same mutation site. Totally 12 Chinese literatures and 394 English literatures were retrieved, among which 96 reported lung involvement only. A total of 10 literatures about Chinese population were screened out from the English literatures, and 115 patients, 31 males and 84 females, were included. The incidence of spontaneous pneumothorax was 66.95% (77/115), while a family history of pneumothorax was 88.31%(68/77). The onset age of spontaneous pneumothorax was between 30 and 44 years. The most common mutation site of FLCN was c.1285dup. Conclusions: BHD syndrome in Asian population may only have lung involvement. Patients with pneumothorax and pulmonary cystic lesions should be inquired of the family history. We speculate that there are many underdiagnosed cases in clinical practice.

[The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020)].

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

Silencing of long non-coding RNA LINC00958 inhibits head and neck squamous cell carcinoma progression and AKT/mTOR signaling pathway by targeting miR-106a-5p.

OBJECTIVE: The long non-coding RNA LINC00958 acts as an oncogenic regulator in many human tumors. In this study, we aimed to investigate the role and potential molecular biological mechanisms of LINC00958 in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Aberrantly expressed LINC00958 was screened out of TCGA database. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to determine LINC00958 and miR-106a-5p expression. Cellular biological behaviors were investigated using CCK-8, colony formation, wound healing and transwell assays. Xenograft mouse models were established to determine the role of LINC00958 in HNSCC growth in vivo. The interaction between LINC00958 and miR-106a-5p was validated by Dual-Luciferase reporter gene assay. Additionally, the underlying pathways affected by LINC00958 were measured by Western blot. RESULTS: LINC00958 expression was upregulated in HNSCC tissues and cells. High LINC00958 level was correlated with the poor prognosis of HNSCC patients. Functional assays showed that the knockdown of LINC00958 inhibited HNSCC malignant phenotypes in vitro and in vivo. Mechanistically, miR-106a-5p was a potential target of LINC00958, and its expression was negatively regulated by LINC00958 in HNSCC. LINC00958 could activate AKT/mTOR signaling pathway, which was mediated by miR-106a-5p. CONCLUSIONS: Taken together, our results suggest that LINC00958 acts as an oncogenic role in HNSCC and activates AKT/mTOR signaling pathway by sponging miR-106a-5p. LINC00958 may serve as a potential target for HNSCC diagnosis and treatment.

[Ultrastructural study of ampulla of mouse inner ear].

Objective: To observe the ultrastructure of the ampulla, and analyze its physiological and pathological significance. Methods: In this study, 20 Kunming mice were used, and scanning electron microscopy was used to observe the ultrastructure of the ampulla of inner ear. Results: Otoconia was found among the cilia bundles of different haircell(intercilla otoconia of ampulla). The cupula was attached to the lateral wall of the ampulla, and easily to be separated; after separated, a kind of slender crystal(surface otoconia of ampulla) could be seen between the cupula and lateral wall of the ampulla, both sides of ampullary crest were covered with slender crystals too. On the canal side of the ampulla wall, there was more particulate matter attached to the wall near the bottom of ampullary crest, partially embedded in the wall, and less on the utricle side of the ampulla wall. Conclusions: The observation of the ultrastructure of the ampulla is helpful for better understanding the physiological functions of the semicircular canals and the ampulla, and better understanding the pathogenesis and solution of some vertigo diseases.

Long non-coding RNA OIP5-AS1 promotes proliferation of gastric cancer cells by targeting miR-641.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of various tumors. Currently, lncRNA OPI5-AS1 (OPI5-AS1) has been identified as a tumor suppressor gene involved in several cancers. Therefore, the aim of this study was to investigate the function of OPI5-AS1 in gastric cancer (GC) progression. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expressions of OPI5-AS1 and microRNA-641 (miR-641) in tissues and cells. The Cell Counting Kit-8 (CCK-8), colony formation, and 5-Ethynyl-2'-deoxyuridine (EDU) assays were used to verify the effect of OPI5-AS1 on cell proliferation. Cell cycle distribution was detected by flow cytometry. Furthermore, Western blot was performed to detect the protein expressions of cyclin D1 and p-AKT. RESULTS: OPI5-AS1 was significantly upregulated, while miR-641 was downregulated in GC tissues and cells. OPI5-AS1 expression was remarkably inversely correlated with miR-641 in GC. Moreover, OPI5-AS1 could sponge miR-641 and regulate its expression in GC cells. Functional experiments showed that OPI5-AS1 overexpression remarkably accelerated GC cell proliferation and cell cycle. However, miR-641 overexpression could reverse the functional effects induced by OPI5-AS1 overexpression. CONCLUSIONS: OPI5-AS1 overexpression promotes tumorigenesis and development of GC by sponging miR-106a-5p. In addition, our findings suggest that OPI5-AS1 may serve as an innovative and prospective therapeutic target for GC.

Influence of miR-199a on rats with non-small cell lung cancer via regulating the HIF-1α/VEGF signaling pathway.

OBJECTIVE: Micro-ribonucleic acids (miRNAs) are involved in the occurrence of various cancers, and the hypoxia-inducible factor 1-α (HIF-1α) is the main regulator of cell proliferation induced by hypoxia. The relationships of miR-199a and HIF-1α expressions with non-small cell lung cancer (NSCLC) remain unclear, so they were explored in this work. MATERIALS AND METHODS: On the basis of establishing the rat model of NSCLC, the messenger RNA (mRNA) expressions of miR-199a, HIF-1α and the vascular endothelial growth factor (VEGF) were analyzed in NSCLC rats, and the correlations of miR-199a with the mRNAs of HIF-1α and VEGF and cancer staging were investigated. To further study the role of miR-199a in NSCLC cell proliferation via the HIF-1α/VEGF signaling pathway, NSCLC cells were treated with the signaling pathway inhibitor and transfected with miR-199a mimics, respectively. Also,  the roles of the inhibitor PX-478 and miR-199a mimics in the expressions of miR-199a, HIF-1α, and VEGF proteins, as well as their influences on cell proliferation ability were detected. RESULTS: In NSCLC rats, the expression of miR-199a was substantially decreased (p<0.01), but the expressions of HIF-1α and VEGF were notably raised (p<0.01). MiR-199a was negatively correlated with the expression of VEGF. As cancer developed, the expression of miR-199a was gradually lowered, but the expressions of HIF-1α and VEGF were gradually increased. Both HIF-1α/VEGF signaling pathway inhibitor PX-478 and miR-199a mimics significantly reduced the expressions of HIF-1α and VEGF proteins (p<0.01) and suppressed the cell proliferation activity. CONCLUSIONS: MiR-199a prevents the proliferation of NSCLC cells via the targeted down-regulation of the HIF-1α/VEGF signaling pathway.

[Protective effect of the histone deacetylase inhibitor ACY1215 against brain edema in mice with acute liver failure].

Objective: To investigate the protective effect of ACY1215 (Rocilinostat), a histone deacetylase inhibitor, against brain edema in mice with acute liver failure. Methods: Lipopolysaccharide combined with D-galactosamine was used to establish a mouse model of acute liver failure, and ACY1215 was used for intervention. The effect of ACY1215 on histopathological changes of the liver was observed after 24 hours, as well as the changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood ammonia, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), brain water content, blood-brain barrier structure, NF-κB-p65, histone, acetylated histone, and TNF-α mRNA in brain tissue. Results: The mice with acute liver failure had marked pathological damage in liver tissue, as well as significant increases in the levels of ALT, AST, blood ammonia, TNF-α, and IFN-γ (t≥5.367, all P < 0.05). ACY1215 significantly improved the pathological damage in liver tissue and reduced the serum levels of ALT, AST, blood ammonia, TNF-α, and IFN-γ (t≤-3.515, all P < 0.05). ACY1215 also significantly reduced the expression of NF-κB-p65 (t = -5.871, P = 0.004) and the mRNA expression of TNF-α (t = -11.913, P < 0.01) in brain tissue and brain water content (t = -2.355, P < 0.01). According to the results of electron microscopy, the model group had an abnormal blood-brain barrier structure, and the ACY1215 group had slighter damage than the model group. Compared with the normal group, the model group had significant increases in the acetylation level of histone H3 and H4 in brain tissue (t≥3.009, both P < 0.05), while ACY1215 further upregulated the acetylation levels of histone H3 and H4 (t≥6.682, both P < 0.05). Conclusion: ACY1215 exerts a protective effect against brain edema in mice with acute liver failure, possibly by regulating histone acetylation and inhibiting inflammation.

[The ultrastructure of utricular maculae of mouse].

Objective: Using scanning electron microscope to observe the ultrastructure of utricular maculae of mouse. Methods: Ten young (6 to 8 weeks) and ten old (>12 months) mice were executed, and their utricles were harvested and the specimens were processed, using scanning electron microscope to observe the structures of the utricles from the surface of otoconia layer to the roots of hair cell cilia. Results: Under the scanning electron microscope, several ultrastructures were observed, including otoconia layer, unstructured gelatinous extracellular matrix layer, honeycomb-like gelatinous extracellular matrix layer, inter-cilia otoconia and hair cell cilia associated with these structures. When compared with young mouse, the otoconia surface of aged mouse was smoother, the gelatinous extracellular matrix between the adjacent otoconias was thinner. Conclusions: Using SEM, ultrastructures can be clearly observed from surface otoconia layer to the roots of hair cell cilia. By the analysis of the ultrastructure of utricular maculae, it is helpful for investigation of the pathological mechanisms of vestibular diseases, such as otolith diseases.

Long Non-Coding RNA: An Emerging Paradigm of Pancreatic Cancer.

Pancreatic cancer remains a worldwide issue and burden that is hard to resolve given its low resection rate and chemo-resistance. Early diagnosis and early treatment are critical for conquering pancreatic cancer. Therefore, new biomarkers for diagnosis and prognosis are urgently needed. Previously, researchers mainly focused on protein-coding genetic and epigenetic changes in many types of cancers, and regarded the noncoding part as waste. Recently, however, long non-coding RNA (lncRNA) has emerged as a major participant in carcinogenesis, as it regulates cell proliferation, migration, invasion, metastasis, chemo-resistance, etc. The underlying mechanisms are summarized as signaling, decoy, guide and scaffold, yet the specific regulation networks remain to be uncovered. Several studies have revealed that some lncRNAs are dysregulated in pancreatic cancer, participating in biological functions. In this review, we will briefly outline the functional lncRNAs in pancreatic cancer, decipher possible mechanisms of lncRNAs, and further explore their significance in pancreatic cancer.

MiR-181a upregulation is associated with epithelial-to-mesenchymal transition (EMT) and multidrug resistance (MDR) of ovarian cancer cells.

OBJECTIVE: Elevated miR-181a is associated with the transition of ovarian tissues from normal into a cancerous state. However, its regulative effect on multidrug resistance (MDR) of ovarian cancer is not quite clear. Therefore, this study aimed to investigate its regulative effects on epithelial-to-mesenchymal transition (EMT) and MDR in ovarian cancer. MATERIALS AND METHODS: The expression profile of miR-181a in normal and ovarian cancer tissues was firstly quantified using qRT-PCR analysis. Then, human ovarian cancer cell line SKOV3 were transfected for miR-181a overexpression and the paclitaxel-resistant variant SKOV3/PTX cells were transfected for miR-181a knockdown. The effect of miR-181a overexpression/knockdown on EMT and PTX sensitivity were studied. RESULTS: MiR-181a level in chemoresistant (CR) cancer tissues were significantly higher than in chemosensitive (CS) cancer tissues and in normal tissue. SKOV3/PTX cells had significantly higher expression of miR-181a and N-cadherin than SKOV3 cells. SKOV3 cells had decreased E-cadherin expression and increased N-cadherin expression after enforced miR-181a expression, while SKOV3/PTX cells had increased E-cadherin expression and decreased N-cadherin expression after miR-181a knockdown. SKOV3 cells had increased P-gp expression after enforced miR-181a expression. Following MTT assay and flow cytometry analysis both confirmed that miR-181a overexpression decreased the PTX sensitivity of SKOV3 cells and while miR-181a inhibition increased the sensitivity of SKOV3/PTX cells. CONCLUSIONS: MiR-181a is an important oncomiR significantly increased in chemoresistant ovarian cancer. Its upregulation is associated with increased level of EMT and decreased cell apoptosis induced by PTX treatment.

[Influence of sevoflurane concentration and stimulation voltage on motor evoked potentials in intraspinal tumor surgery].

OBJECTIVE: To evaluate the effects of increasing end-tidal concentrations of sevoflurane and increasing stimulation voltage on motor evoked potentials, so as to provide evidence in making anesthesia plan for intraspinal tumor surgery. METHODS: In the study, 48 patients scheduled to undergo intraspinal tumor surgery [American Society of Anesthesiology,(ASA) I-II, 18-65 years old] were enrolled. After general anesthesia induction, the patients were assigned to receive sevoflurane anesthesia of increasing end-tidal concentration in the sequence of 0.0%, 0.5%, 1.0% and 1.5% respectively, under a background of propofol and remifentanil. All the observations were done before the important steps of surgery. Remifentanil infusion rate was 0.2 µg /(kg×min), while the propofol infusion rate was adjusted to maintain the bispectral index values within the range of 30-50. At each concentration, 4 stimulation voltages of 300 V, 400 V, 500 V and 600 V were employed to elicit motor evoked potentials (MEPs). The amplitude and latency of each MEP were compared. The success ratio was also recorded. RESULTS: The concentration of sevoflurane and the stimulation voltage had impacts on the amplitude and latency of MEPs. Under each stimulation voltage, the MEPs amplitude decreased following increasing end-tidal sevoflurane concentrations, and significant differences were found in comparing 1.5% sevoflurane (left 20.50 µV, 70.71 µV, 135.97 µV, 190.00 µV , right 14.29 µV, 50.71 µV, 73.10 µV, 77.50 µV) with 0.0% sevoflurane (left 143.00 µV, 388.10 µV, 484.53 µV, 500.00 µV, right 176.00 µV, 407.60 µV, 384.35 µV, 451.00 µV) and 0.5% sevoflurane (left 100.00 µV, 362.57 µV, 444.05 µV, 435.00 µV, right 115.00 µV, 207.15 µV, 258.34 µV, 358.50 µV), left χ(2)= 27.46,P<0.01, right χ(2)= 60.49,P<0.01; left χ(2)= 20.73,P<0.01, right χ(2)= 55.05,P<0.01;left χ(2)= 34.25,P<0.01,right χ(2)=33.58,P<0.01;left χ(2)= 28.61,P<0.01 ,right χ(2)= 49.04,P<0.01; while there were no statistical differences in the latency changes (P=0.26). Under each end-tidal sevoflurane concentration, the MEPs amplitude increased following increasing stimulation voltages, and significant differences were found in comparing 300 V (left 143.00 µV, 100.00 µV, 61.50 µV, 20.50 µV , right 176.00 µV, 115.00 µV, 41.07 µV, 14.29 µV) with 400 V (left 388.10 µV, 362.57 µV, 198.81 µV, 70.71 µV, right 407.60 µV, 207.15 µV, 89.00 µV, 50.71 µV) and 500 V (left 484.53 µ V, 444.05 µV, 216.24 µV, 135.97 µV, right 384.35 µV, 258.34 µV, 187.50 µV, 73.10 µV) and 600 V (left 500.00 µV, 435.00 µV, 344.00 µV, 190.00 µV, right 451.00 µV, 385.50 µV, 156.00 µV, 77.50 µV), left χ(2)= 45.55,P<0.01, right χ(2)= 25.73,P<0.01; left χ(2)= 46.67,P<0.01, right χ(2)= 55.30,P<0.01;left χ(2)= 47.36,P<0.01,right χ(2)= 47.82,P<0.01; left χ(2)= 38.67,P<0.01, right χ(2)= 45.87,P<0.01; while the latencies were decreased, and significant differences were found in comparing 300 V with 400 V and 500 V and 600V(left F=7.50,P=0.01 , right F=13.33,P<0.01), but the differences had little clinical significance. The success ratio decreased by increasing end-tidal sevoflurane concentration, and significant differences were found in comparing 1.5% sevoflurane (left 43.8%,70.8%, 77.1%,81.3%, right 37.5%,60.4%,75.0%,66.7%) with 0.0% sevoflurane (left 79.2%,87.5%,95.8%,93.8%, right 75.0%,95.8%,95.8%, 95.8%) and 0.5% sevoflurane (left 72.9%,89.6%,95.8%,95.8%, right 66.7%,89.6%,95.8%, 97.9%); the success ratio increased by increasing stimulation voltage, and significant differences were found in comparing 300 V(left 79.2%,72.9%,62.5%,43.8%, right 75.0%,66.7%,60.4%, 37.5%)with 400 V(left 87.5% ,89.6%,77.1%,70.8% , right 95.8%,89.6%,79.2%,60.4%)and 500 V(left 95.8%,95.8%,91.7%,77.1%, right 95.8%,95.8%,81.3%,75.0%)and 600 V (left 93.8%, 95.8%,89.6%,81.3%, right 95.8%,97.9%,89.6%,66.7%), but there were no statistical differences in the success ratio of MEPs between the group with stimulation voltage of 600 V , end tidal sevoflurane concentration of 1.5% and the group with stimulation voltage of 300 V, end tidal sevoflurane concentration of 0.0% (P=0.22). CONCLUSION: Sevoflurane inhibited MEPs in a dose-dependent manner. It can decrease the amplitudes and prolong the latencies. But increasing stimulation voltage will facilitate MEPs monitoring and increase the success ratio. Sevoflurane can be used in larger parts of MEPs monitoring surgery by increasing the stimulation voltage.

Cytotoxic constituents of Lasiosphaera fenzlii on different cell lines and the synergistic effects with paclitaxel.

The fruit body of Lasiosphaera fenzlii was found to show cytotoxicity on cancer cells during a preliminary screening. Repeated column chromatography of the fungal methanol extract resulted in the isolation of six compounds identified as 5α,8α-epidioxy-ergosta-6,22-dien-3ß-ol (1), 5α,8α-epidioxy-ergosta-6,9(11),22-trien-3ß-ol (2), 5α-ergosta-7,22-dien-3ß-ol (3), 5α-ergosta-7,22-dien-3-one (4), ergosta-7,22-dien-3ß,5α,6ß-triol (5) and 6-dihydroxy-2,3-dihydro-1H-isoindol-1-one (6). The two peroxide compounds, 1 and 2, showed cytotoxic activity and compound 1 was selectively cytotoxic to cancer cells. Furthermore, compound 1 synergised the cytotoxicity of paclitaxel on Hela cells by increasing intracellular accumulation of paclitaxel in cancer cells but not in normal cells.

Association of Resting Heart Rate with Infrarenal Aortic Diameter: A Cross Sectional Study in Chinese Hypertensive Adults.

OBJECTIVE: Elevated resting heart rate (RHR) has been shown to be a risk marker for cardiovascular disease. Results from studies on the effects of RHR in large arteries are limited to the functional changes of those arteries, while the association between RHR and aortic diameter remains largely understudied. METHODS: This was a cross sectional study of hypertensive Chinese adults from rural areas. The maximum infrarenal aortic diameter (maxIAD) from renal arteries to the iliac bifurcation was obtained by ultrasound. MaxIADs in different RHR groups were compared in males and females separately because of the significant differences between sexes. Multiple regression analysis was used to determinate the correlation between RHR and maxIAD. Further interactions between three factors (BMI, smoking, and anti-hypertensive regimens) and RHR for maxIAD were examined using subgroup analysis. RESULTS: 19,200 subjects were enrolled in the study, with an average age of 64.8±7.4 years and 61.6% females. Only 22 cases (0.11%) were detected with AAA, with males (n = 17) presenting a higher AAA incidence than females (n = 5). In subjects ≥65 years, there were 18 (0.19%) AAA, and 15 (83.3%) had a history of smoking. In the total subjects, the mean maxIAD ranged from 15.7±2.1 mm to 15.2±2.2 mm as RHR changed from the lowest quartile to the highest (≥84 bpm) in males, with a similar tendency observed in females. The correlation coefficient of RHR on maxIAD was -0.17 in males and -0.12 in females. Further subgroup analysis revealed that smoking exaggerated the correlation between RHR and maxIAD, but only in females. CONCLUSIONS: A low AAA incidence was observed in this hypertensive Chinese population. There was a negative association between RHR and maxIAD, potentially exaggerated by smoking, especially in females.

The role of IVS14+1 G > A genotype detection in the dihydropyrimidine dehydrogenase gene and pharmacokinetic monitoring of 5-fluorouracil in the individualized adjustment of 5-fluorouracil for patients with local advanced and metastatic colorectal cancer: a preliminary report.

AIM: We retrospectively investigated the relationship between IVS14+1 G > A genotype of the dihydropyrimidine dehydrogenase (DPD) gene with plasma concentration of 5-fluorouracil (5-FU) as well as adverse reactions in 80 patients with locally advanced or metastatic colorectal cancer. PATIENTS AND METHODS: Eighty patients with un-resectable locally advanced or metastatic colorectal cancer were treated with Folfox-6 regimen, which repeated every two weeks for at least three cycles. Single nucleotide polymorphisms for DPD gene were analyzed before chemotherapy by high-resolution melting (HRM) analysis. The plasma concentration of fluorouracil was measured by high performance liquid chromatography (HPLC) after continuous infusion of fluorouracil over 12 h in each cycle. The average values of plasma concentrations in each cycle were calculated, and the factors related to plasma concentration of 5-FU were screened by stepwise regression. RESULTS: All patients were divided into three groups according to the predictive confidence interval of plasma concentration of 5-FU, and the average plasma concentrations of fluorouracil in each cycle of these three groups were less than or equal to 26.83 mg/L, 26.83-40.62 mg/L, and more than 40.62 mg/L, respectively. Stepwise regression analysis showed that the plasma concentration of fluorouracil was associated with myelosuppression, hand-foot syndrome, diarrhea, overall survival (OS) and DPD genotype. In efficacy, the median progression-free survival PFS (mPFS) and OS (mOS) of group 2 and group 3 were both significantly higher than those of group 1. CONCLUSIONS: Among the advanced colorectal cancer patients receiving fluorouracil-based chemotherapy, those with plasma concentration of 5-FU above 26.83 mg/L can obtain better survival; for patients with heterozygous DPD IVS14+1 mutation, 5-FU dose should be appropriately reduced according to last plasma concentration to reduce adverse reactions, while the homozygous ones should avoid application of 5-FU and its derivatives.