Nanoscale Two-Dimensional FeII- and CoII-Based Metal-Organic Frameworks of Porphyrin Ligand for the Photodynamic Therapy of Breast Cancer.

The delivery of biocompatible reagents into cancer cells can elicit an anticancer effect by taking advantage of the unique characteristics of the tumor microenvironment (TME). In this work, we report that nanoscale two-dimensional FeII- and CoII-based metal-organic frameworks (NMOFs) of porphyrin ligand meso-tetrakis (6-(hydroxymethyl) pyridin-3-yl) porphyrin (THPP) can catalyze the generation of hydroxyl radicals (•OH) and O2 in the presence of H2O2 that is overexpressed in the TME. Photodynamic therapy consumes the generated O2 to produce a singlet oxygen (1O2). Both •OH and 1O2 are reactive oxygen species (ROS) that inhibit cancer cell proliferation. The FeII- and CoII-based NMOFs were non-toxic in the dark but cytotoxic when irradiated with 660 nm light. This preliminary work points to the potential of porphyrin-based ligands of transition metals as anticancer drugs by synergizing different therapeutic modalities.

A Multi-Element Identification System Based on Deep Learning for the Visual Field of Percutaneous Endoscopic Spine Surgery.

Background: Lumbar disc herniation is a common degenerative lumbar disease with an increasing incidence. Percutaneous endoscopic lumbar discectomy can treat lumbar disc herniation safely and effectively with a minimally invasive procedure. However, the learning curve of this technology is steep, which means that initial learners are often not sufficiently proficient in endoscopic operations, which can easily lead to iatrogenic damage. At present, the application of computer deep learning technology to clinical diagnosis, treatment, and surgical navigation has achieved satisfactory results. Purpose: The objective of our team is to develop a multi-element identification system for the visual field of endoscopic spine surgery using deep learning algorithms and to evaluate the feasibility of this system. Method: We established an image database by collecting surgical videos of 48 patients diagnosed with lumbar disc herniation, which was labeled by two spinal surgeons. We selected 6000 images of the visual field of percutaneous endoscopic spine surgery (including various tissue structures and surgical instruments), divided into the training data, validation data, and test data according to 2:1:2. We developed convolutional neural network models based on instance segmentation-Solov2, CondInst, Mask R-CNN and Yolact, and set the four network model backbone as ResNet101 and ResNet50 respectively. Mean average precision (mAP) and frames per second (FPS) were used to measure the performance of each model for classification, localization and recognition in real time, and AP (average) is used to evaluate how easily an element is detected by neural networks based on computer deep learning. Result: Comprehensively comparing mAP and FSP of each model for bounding box test and segmentation task for the test set of images, we found that Solov2 (ResNet101) (mAP = 73.5%, FPS = 28.9), Mask R-CNN (ResNet101) (mAP = 72.8%, FPS = 28.5) models are the most stable, with higher precision and faster image processing speed. Combining the average precision of the elements in the bounding box test and segmentation tasks in each network, the AP(average) was highest for tool 3 (bbox-0.85, segm-0.89) and lowest for tool 5 (bbox-0.63, segm-0.72) in the instrumentation, whereas in the anatomical tissue elements, the fibrosus annulus (bbox-0.68, segm-0.69) and ligamentum flavum (bbox-0.65, segm-0.62) had higher AP(average),while extra-dural fat (bbox-0.42, segm-0.44) was lowest. Conclusion: Our team has developed a multi-element identification system for the visual field of percutaneous endoscopic spine surgery adapted to the interlaminar and foraminal approaches, which can identify and track anatomical tissue (nerve, ligamentum flavum, nucleus pulposus, etc.) and surgical instruments (endoscopic forceps, an high-speed diamond burr, etc.), which can be used in the future as a virtual educational tool or applied to the intraoperative real-time assistance system for spinal endoscopic operation.

Targeting STING-mediated pro-inflammatory and pro-fibrotic effects of alveolar macrophages and fibroblasts blunts silicosis caused by silica particles.

Silica is utilized extensively in industrial and commercial applications as a chemical raw material, increasing its exposure and hazardous potential to populations, with silicosis serving as an important representative. Silicosis is characterized by persistent lung inflammation and fibrosis, for which the underlying pathogenesis of silicosis is unclear. Studies have shown that the stimulating interferon gene (STING) participates in various inflammatory and fibrotic lesions. Therefore, we speculated that STING might also play a key role in silicosis. Here we found that silica particles drove the double-stranded DNA (dsDNA) release to activate the STING signal pathway, contributing to alveolar macrophages (AMs) polarization by secreting diverse cytokines. Then, multiple cytokines could generate a micro-environment to exacerbate inflammation and promote the activation of lung fibroblasts, hastening fibrosis. Intriguingly, STING was also crucial for the fibrotic effects induced by lung fibroblasts. Loss of STING could effectively inhibit silica particles-induced pro-inflammatory and pro-fibrotic effects by regulating macrophages polarization and lung fibroblasts activation to alleviate silicosis. Collectively, our results have revealed a novel pathogenesis of silica particles-caused silicosis mediated by the STING signal pathway, indicating that STING may be regarded as a promising therapeutic target in the treatment of silicosis.

CCL12 induces trabecular bone loss by stimulating RANKL production in BMSCs during acute lung injury.

In the last three years, the capacity of health care systems and the public health policies of governments worldwide were challenged by the spread of SARS-CoV-2. Mortality due to SARS-CoV-2 mainly resulted from the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Moreover, millions of people who survived ALI/ARDS in SARS-CoV-2 infection suffer from multiple lung inflammation-induced complications that lead to disability and even death. The lung-bone axis refers to the relationship between lung inflammatory diseases (COPD, asthma, and cystic fibrosis) and bone diseases, including osteopenia/osteoporosis. Compared to chronic lung diseases, the influence of ALI on the skeleton has not been investigated until now. Therefore, we investigated the effect of ALI on bone phenotypes in mice to elucidate the underlying mechanisms. In vivo bone resorption enhancement and trabecular bone loss were observed in LPS-induced ALI mice. Moreover, chemokine (C-C motif) ligand 12 (CCL12) accumulated in the serum and bone marrow. In vivo global ablation of CCL12 or conditional ablation of CCR2 in bone marrow stromal cells (BMSCs) inhibited bone resorption and abrogated trabecular bone loss in ALI mice. Furthermore, we provided evidence that CCL12 promoted bone resorption by stimulating RANKL production in BMSCs, and the CCR2/Jak2/STAT4 axis played an essential role in this process. Our study provides information regarding the pathogenesis of ALI and lays the groundwork for future research to identify new targets to treat lung inflammation-induced bone loss.

[Study on the correlation between the thickness of superficial fascia at Dazhui(GV14) and cervical spondylosis].

OBJECTIVE: To observe the correlation between the thickness of superficial fascia at Dazhui (GV14) acupoint and cervical spondylosis, so as to explore the essence of its morphological and structural changes of acupoint sensitivity. METHODS: A retrospective study was conducted. According to the diagnostic criteria of "Guidelines for Diagnosis, Treatment and Rehabilitation of Cervical Spondylosis" (2017), 344 cases of cervical spine magnetic resonance imaging (MRI) examination were included and divided into control group (73 cases) and observation group (271 cases). The control group was healthy population, and the observation group was patients with cervical spondylosis conforming to the diagnostic criteria, including cervical spondylosis of neck type, cervical spondylosis radiculopathy, cervical spondylotic myelopathy, cervical spondylosis of vertebral artery type, and sympathetic cervical spondylosis. According to MRI images of cervical spine, the structure of GV14 acupoint including skin, superficial fascia layer and aponeurosis ligament layer were measured. RESULTS: The acupoint depth and the superficial fascia thickness at GV14 in the observation group were (56.6±8.8) mm and (22.8±7.6) mm, the acupoint depth and the superficial fascia thickness at GV14 were (49.8±7.0) mm and (16.6±6.6)mm in the control group, which were significantly greater in the observation group than in the control group (P<0.01). The superficial fascia thickness at GV14 of cervical spondylotic mye-lopathy, cervical spondylosis of neck type and cervical spondylosis radiculopathy in the observation group was (23.8±8.1)mm, (23.0±7.3)mm and (22.6±6.5)mm, the acupoint depth of GV14 was (58.7±8.8)mm, (56.2±9.1)mm and (55.8±6.4)mm, which were significantly thicker than the superficial fascia thickness and the acupoint depth in the control group (P<0.01). In the observation group，the superficial fascia thickness of GV14 of cervical spondylosis myelopathy was significantly thicker than those of sympathetic cervical spondylosis (17.8±8.1) mm and cervical spondylosis of vertebral artery type (19.9±5.9) mm (P<0.01, P<0.05). In the observation group, the depth of GV14 of cervical spondylosis myelopathy was thicker than that of cervical spondylosis of neck type, cervical spondylosis radiculopathy, sympathetic cervical spondylosis and cervical spondylosis of vertebral artery type(P<0.05，P<0.01)； the depth of GV14 of sympathetic cervical spondylosis was thinner than that of cervical spondylosis of neck type and cervical spondylosis radiculopathy (P<0.01). CONCLUSION: The superficial fascia thickness at GV14 was correlated with cervical spondylosis, and it is also related to cervical spondylotic myelopathy, cervical spondylosis of neck type and cervical spondylosis radiculopathy. The morphological and structural changes of GV14 in the state of cervical spondylosis were mainly the thickness of the superficial fascia.

Research on run-time risk evaluation method based on operating scenario data for autonomous train.

Recent years witness the focus of the research of next-generation railways on risk situation awareness and safety decision-making to enhance the autonomy of unmanned trains. However, complex environmental factors make it difficult to assess the risks of train operation. Thus, it is of great necessity to clearly monitor the scenario parameters under which the train control system is designed to work, and to infer real-time risk through the collected scenario data. This paper first clarifies the key scenario parameters that need to be collected during the operation according to the concept of Operational Design Domain (ODD) and operating scenario. The key parameters and their dependencies are used to derive the Dynamic Bayesian Network (DBN) structure. Second, for data probability uncertainty, Fuzzy Set Theory is introduced, within the framework of which a fuzzy dynamic reasoning process is presented by monitoring the scenario data deviation. Finally, a case of real-time risk evaluation and analysis of the accident of Singapore MTR is explicated to demonstrate its contribution to operating data-based runtime risk analysis.

Inhibition of Galectin-3 attenuates silica particles-induced silicosis via regulating the GSK-3ß/ß-catenin signal pathway-mediated epithelial-mesenchymal transition.

Silica is a very common and important chemical raw material with a wide range of uses. Long-term inhalation of silica particles could cause lung toxicity, of which the most important representative is silicosis. Silicosis is a serious and fatal occupational pulmonary disease, characterized by persistent pulmonary inflammation and fibrosis. Despite intensive research, the toxic mechanism of silicosis caused by silica particles is not completely clear, which deserves further research and exploration. Many studies have indicated that the epithelial cells partially participate in the formation, accumulation, and activation of fibroblasts through epithelial-mesenchymal transition (EMT), which is conducive to the occurrence of fibrosis. Galectin-3 (Gal-3), widely expressed in epithelial cells, was observed to induce EMT in fibrotic diseases and tumors by regulating the GSK-3ß and ß-catenin. Previous studies have demonstrated that silica particles is indeed involved in the silicosis process by inducing EMT. However, it remains to be further studied whether there is a certain relationship between silica particles and Gal-3 expression, and whether Gal-3 also mediates the development of the silica particles-induced silicosis by regulating GSK-3ß/ß-catenin signal pathway-mediated EMT. Our research results showed that silica particles could significantly induce Gal-3 expression to promote the development of EMT through activating the GSK-3ß/ß-catenin signal pathway in mice and in A549 cells, which then significantly exacerbated the pulmonary fibrosis caused by silica particles. And the inhibition of Gal-3 could effectively inhibit the occurrence of EMT, and then effectively alleviate silicosis caused by silica particles. These findings would help us to further clarify the toxicological mechanisms of silicosis caused by silica particles and provide a novel target for prevention and intervention of silicosis.

Percutaneous endoscopic lumbar discectomy via the medial foraminal and interlaminar approaches: A comparative study with 2-year follow-up.

Objective: The purpose of this study was to analyze the clinical effect of percutaneous endoscopic medial foraminal discectomy (PEMFD) in the treatment of lumbar disc herniation (LDH). Methods: We retrospectively examined and compared clinical data from 39 single-level LDH patients who underwent PEID and 47 who underwent PEMFD. All the patients were diagnosed with single-level LDH and were treated in Xuzhou Central Hospital for single-segmental lumbar disc herniation between June 2017 and December 2019. Collect and count surgical-related indicators, intraoperative bleeding volume and 24-hour postoperative drainage volume, lower extremity numbness Visual Analogue Scale (VAS), the pain VAS and lumbar Oswestry Disability Index (ODI) scores. Results: Intraoperative bleeding volume and 24-hour postoperative drainage volume were significantly lower in the PEMFD group (p < 0.05). Operation time and length of hospital stay did not significantly differ between the groups. Transient spinal cord injury and surgical site infection did not occur. Recurrence occurred in two patients in each group. Repeat surgery in these patients demonstrated remarkable epidural scarring in the PEID group patients; no scarring was evident in the PEMFD group patients. The numbness VAS score 72 h after surgery and the pain VAS and ODI scores 1 month after surgery significantly differed between groups; however, pain VAS and ODI scores 6, 12, and 24 months after surgery did not. At last follow-up, the modified MacNab criteria outcome did not significantly differ between the groups. Conclusion: PEMFD and PEID have similar short- and medium-term outcomes. However, PEMFD has several advantages: simplicity, lower bleeding volume, and preservation of the LF.

Similarities and differences between Mn(II) and Zn(II) coordination polymers supported by porphyrin-based ligands: synthesis, structures and nonlinear optical properties.

Four coordination polymers (CPs) Mn-TMPP (1), Zn-TMPP (2), Mn-THPP (3), and Zn-THPP (4) have been synthesized and characterized (H2TMPP = meso-tetrakis (6-methylpyridin-3-yl) porphyrin; H2THPP = meso-tetrakis (6-(hydroxymethyl) pyridin-3-yl) porphyrin). The one-dimensional (1D) chain compound 1 is formed via a head-to-tail connection of the Mn-TMPP unit, wherein the central Mn2+ features a square pyramidal geometry coordinated by four N atoms from the porphyrin skeleton and one additional N atom from an adjacent Mn-TMPP unit. Compound 2 features an octahedral Zn2+ center associated with four N atoms from the porphyrin skeleton to define the equatorial plane and two additional N donors at the axial positions to give a two-dimensional (2D) CP. The 1D chain of 1 and the 2D layer of 2 possess distinctive molecular structures but nearly identical molecular arrangements in their unit cells viewed along all three crystallographic axes. By contrast, Mn- and Zn-based CPs 3 and 4 supported by the THPP ligand share both identical molecular connectivities and crystal packing. In 3/4, each Mn/Zn center is chelated by four N donors of the porphyrin interior to define the equatorial plane of an octahedron, whose axial sites are occupied by two alcoholic OH groups from a pair of trans-located pyridinemethanol moieties. The third-order nonlinear optical properties of 1-4 investigated using the Z-scan technique at 532 nm revealed reverse saturable absorption and self-focusing effects for all four CPs, with hyperpolarizability values (γ) in the range 1.42 × 10-28 esu to 7.64 × 10-28 esu. These high γ values are comparable to the best porphyrin-based molecular assemblies, demonstrating potential for these materials in optical limiting applications.

Zinc and Cadmium Complexes of Pyridinemethanol Carboxylates: Metal Carboxylate Zwitterions and Metal-Organic Frameworks.

The heterofunctional lactone furo[3,4-b]pyridin-5(7H)-one (L1 ) undergoes a coordination-induced ring-opening reaction with Zn(NO3 )2 ⋅ 6H2 O to yield the zwitterionic [Zn(L1 ')2 (H2 O)2 ] (1, L1 '=2-(hydroxymethyl)nicotinate) with an uncoordinated carboxylate. The same reaction with Cd(NO3 )2 ⋅ 4H2 O provides a two-dimensional (2D) network of [Cd(L1 ')2 ]n (3) with the carboxylates coordinated to cadmium(II) propagating the assembly. The corresponding reactions of Zn(NO3 )2 ⋅ 6H2 O and Cd(NO3 )2 ⋅ 4H2 O with 2-(hydroxymethyl)isonicotinic acid (HL2 ) generated zwitterionic [Zn(L2 )2 (H2 O)2 ] (2) and a 2D network [Cd(L2 )2 ]n ⋅nDMF (4, DMF=N,N'-dimethylformamide), respectively. Complexes 1-4 are weakly emissive, giving ligand-centered emissions at 409 nm (1), 412/436 nm (2), 404 nm (3), and 412/436 nm (4) in CHCl3 solutions upon excitation at 330 nm. This work points to the potential of using 'hidden' functionalities widely found in small organic molecules and natural products for the construction of coordination complexes with new functionality and potential applications.

Morphology-dependent third-order optical nonlinearity of a 2D Co-based metal-organic framework with a porphyrinic skeleton.

A two-dimensional (2D) Co-based metal-organic framework (MOF) with porphyrinic skeleton forms crystalline plates, flower-shaped clusters, and ultrathin films under optimized conditions, including the use of polyvinylpyrrolidone (PVP) as a surfactant. Ultrathin films demonstrate the best solution-based third-order nonlinear optical properties, featuring a nonlinear transmittance (T) value of 0.54, absorption coefficient (α2) of 9.5 × 10-10 m W-1 and second hyperpolarizability (γ) value of 1.37 × 10-28 esu, which are slightly better than those of the flower-shaped clusters (T = 0.65, α2 = 7.0 × 10-10 m W-1; γ = 1.27 × 10-28 esu), but marginally better than those of the crystalline thin plates (T = 0.94, α2 = 2.4 × 10-10 m W-1; γ = 0.24 × 10-28 esu).

Effective loading of cisplatin into a nanoscale UiO-66 metal-organic framework with preformed defects.

Defects within the nanoscale UiO-66 metal-organic framework (MOF) are created to lock a hybrid phosphonoacetate ligand through Zr-O-P linkages, leaving the carboxyl group free to anchor cisplatin prodrug cis, cis, trans-[Pt(NH3)2Cl2(OH)2]. A drug loading of 256.5 mg g-1 (25.7 wt% based on cisplatin) was achieved with a Zr6 : Pt : P ratio of 1.5 : 1 : 1, which surpasses defect-free UiO-66 and several other MOF carriers. This framework exhibited a burst release of its payload in PBS solution in the first 2 h, releasing 71% of the drug, including a 50% payload release in less than 1 h. This work demonstrates that MOF defects can be intentionally engineered to achieve a high drug loading, and serves as an alternative to drug encapsulation using the pore void and through the association of the functionalized ligand.

[The change and mechanism of apoptosis in the hippocampal CA1 region of rats exposed to intermittent hypoxia].

OBJECTIVE: To investigate the effect of intermittent hypoxia on rat hippocampal oxidative stress and neuron apoptosis in the hippocampal CA1 region. METHODS: Thirty six healthy male Wistar rats were randomly divided into three groups of 12 each: a control (NC) group, an intermittent hypoxia (IH) group and a sustained hypoxia (SH) group. The levels of Malondialdehyde (MDA) and Superoxide dismutase (SOD) were detected by colorimetric method. Western blotting was used to examine the expression of p-JNK and p-c-jun. TUNEL was used to detect the neuron apoptosis in the hippocampal CA1 region. RESULTS: The level of MDA (nmol/mg protein) in the hippocampal CA1 region in IH group (1.61 +/- 0.39) was significantly higher than those in NC group (1.25 +/- 0.29) and in SH group (1.34 +/- 0.24), F = 4.185, P < 0.05; the level of SOD (NU/mg protein) in IH group (45 +/- 13) was significantly lower than those in NC group (58 +/- 12) and in SH group (56 +/- 10), F = 4.338, P < 0.05. There were no significant differences between SH and NC groups in the level of MDA or in the activity of SOD (P all > 0.05). The expression of p-JNK and p-c-jun in IH group were 2.1 and 2.3 times the expression in the NC group respectively. The apoptotic indices of IH group (0.30 +/- 0.16) was significantly elevated as compared with group NC (0.12 +/- 0.07) and SH (0.17 +/- 0.09), F = 7.766, P < 0.01. CONCLUSION: Oxidative stress associated with IH in the hippocampal CA1 region can activate JNK signaling pathway, leading to the apoptosis of hippocampal neuron. This maybe the pathophysiological basis of obstructive sleep apnea hypopnea syndrome with neurobehavioral impairments.

[Effects of Shen-Mai injection on sternohyoid contractile properties in chronic intermittent hypoxia rat].

OBJECTIVE: To investigate the effect of Shen-Mai injection (SMI) on sternohyoid contractile properties in rats with chronic intermittent hypoxia. METHODS: Thirty healthy male SD rats were randomly assigned to three equal groups, the control group (A group), the chronic intermittent hypoxia group (B group) and the SMI group(C group). Rats in B group and C group were exposed to alternating periods of hypoxia and normoxia once per minute for 8 h/d for 5 weeks in order to mimic the intermittent hypoxia of obstructive sleep apnea-hypopnea syndrome (OSAHS) in humans. Isometric contractile properties were determined by electrostimulating the strips of isolated sternohyoid muscles at different frequencies (from 10 Hz to 100 Hz) to observe the changes of the sternohyoid contractile properties. RESULTS: (1) The tension of sternohyoid muscle in A group at different frequencies was (23.2 +/- 5.6), (26.2 +/- 5.0), (35.1 +/- 5.4), (46.0 +/- 8.5), (57.0 +/- 9.9), (69.9 +/- 9.7), (79.2 +/- 9.5), (85.7 +/- 7.6), (87.9 +/- 7.9), and (86.6 +/- 12.4) g/cm(2). The tension of sternohyoid muscle in B group [(19.5 +/- 4.7), (23.8 +/- 4.7), (33.0 +/- 5.1), (45.1 +/- 5.9), (54.2 +/- 7.0), (66.1 +/- 9.1), (74.2 +/- 9.1), (79.7 +/- 9.0), (82.0 +/- 8.4), and (80.7 +/- 11.8) g/cm(2)] was not significantly different from those in A group respectively (all P > 0.05); while the tension of sternohyoid muscle in C group [(30.5 +/- 2.3), (40.0 +/- 5.4), (56.2 +/- 7.6), (72.2 +/- 6.4), (82.0 +/- 5.5), (92.4 +/- 4.6), (98.1 +/- 4.0), (99.2 +/- 7.4), (101.8 +/- 3.9), and (102.2 +/- 4.0) g/cm(2)] was significantly different from those in B group respectively (all P < 0.05). (2) In fatigue test, the tension percentages of sternohyoid muscle in A group at 1, 2, 3, 4, and 5 min were (87.9 +/- 5.7)%, (72.1 +/- 11.5)%, (55.6 +/- 9.6)%, (39.7 +/- 10.7)%, (33.2 +/- 10.2)%. Compared with A group, the tension percentages of sternohyoid muscle in B group at 1, 2, 3, 4, and 5 min [(75.6 +/- 8.5)%, (41.6 +/- 7.3)%, (29.0 +/- 2.7)%, (20.4 +/- 2.9)%, (18.5 +/- 2.5)%, respectively] decreased significantly (all P < 0.05). Compared with B group, the tension percentages of sternohyoid muscle in C group [(87.9 +/- 4.4)%, (67.9 +/- 14.1)%, (48.4 +/- 9.9)%, (38.2 +/- 7.0)%, (33.8 +/- 9.3)%, respectively] increased significantly (all P < 0.05). CONCLUSIONS: Chronic intermittent hypoxia can increase upper airway muscle fatigue. SMI can significantly increase the contractile properties of upper airway muscle and resist the fatigue of upper airway muscle.

[Effect of shenmai injection and aminophylline on small airway smooth muscle cell apoptosis and related gene expression in rats with emphysema].

OBJECTIVE: To investigate the effect of Shenmai Injection (SMI) and aminophylline on small airway smooth muscle cell (SASMC) apoptosis and the Fas/FasL expression in the papain induced emphysema model rats. METHODS: Emphysema model in rat was established by a single intratracheal instillation of papain. Apoptosis and Fas/FasL expression of SASMC were examined by immunohistochemical SABC and TUNEL assay at 1, 3, 5, 7, 15 and 30 days after modelling, and the effect of SMI and aminophylline on them were observed. RESULTS: Fas, FasL expressions in normal SASMC were very low with a positive rate of (2.31 +/- 0.05)% and (1.28 +/- 0.47)% respectively. After papain instillation, the positive rates increased along with the prolonging of instillation time. SMI showed an inhibition on SASMC Fas and FasL expression but aminophylline didn't show. SASMC apoptosis was very low in normal rats with a rate of (0.87 +/- 0.32)%, it also raised after papain instillation and increased progressively along with the instillation time. SMI treatment could lower the apoptosis rate but aminophylline couldn't. CONCLUSION: Fas and FasL participated the SASMC apoptosis modulation in emphysema formation. SMI shows a definite treatment effect on emphysema by influencing the Fas and FasL protein expression and reducing SASMC apoptosis through inhibiting the release of inflammatory mediator.

[Effect of shenmai injection on L-type calcium channel of diaphragmatic muscle cells in rats].

OBJECTIVE: To explore the effect of Shenmai Injection (SMI) on L-type calcium channel of diaphragmatic muscle cells in rats. METHODS: Single diaphragmatic muscle cell of rats was obtained by the acute enzyme isolation method and the standard whole-cell patch clamp technique was used to record the inward peak L-type calcium current (IPLC) and current-voltage relationship curve of diaphragmatic muscle cells of 7 rats, and to compare the effects of SMI in various concentrations on them. RESULTS: When keeping the electric potential at -80 mV, stimulation frequency 0.5 Hz, clamp time 300 ms, stepped voltage 10 mV, and depolarized to +60 mV, 10 microliters/ml of SMI could only cause the mean IPLC of rat's diaphragmatic muscle cells increased from -6.9 +/- 0.6 pA/pF to -7.5 +/- 0.7 pA/pF, the amplification being (9.2 +/- 2.8)%, comparison between those of pre-treatment and post-treatment showed insignificant difference. But when the concentration of SMI increased to 50 microliters/ml and 100 microliters/ml, the mean IPLC increased to -8.4 +/- 0.6 pA/pF and -9.2 +/- 0.6 pA/pF, respectively, and the amplification was (22.4 +/- 1.7)% and (34.6 +/- 4.6)% respectively, showing significant difference to that of pre-treatment (P < 0.05). However, SMI showed no significant effect on maximal activation potential and reversal potential. CONCLUSION: SMI can activate the calcium channel of diaphragmatic muscle cells in rats, increase the influx of Ca2+, so as to strengthen the contraction of diaphragmatic muscle, which may be one of the ionic channel mechanisms of SMI in treating diaphragmatic muscle fatigue in clinical practice.

[Effect of Shen-Mai injection and aminophylline on diaphragmatic muscle cell apoptosis and related gene expression in rats with chronic hypoxia].

OBJECTIVE: To investigate the effect of Shen-Mai injection (SMI) and aminophylline on diaphragmatic muscle cell apoptosis and the Fas/FasL expression in chronic hypoxic rats. METHODS: Seventy-five male Wistar rats were randomly divided into three equal groups, control group (A group), SMI group (B group) and aminophylline group (C group). Then each group was further divided into five subgroups of pre-hypoxia, hypoxia 1 w, 2 w, 3 w and 4 w groups (5 rats each). The concentration of oxygen was (10 +/- 3)%, 7 d/w, 8 h/d for all groups, but only B group and C group received SMI (2 ml/d) and aminophylline (10 mg/kg) respectively. Apoptosis and Fas/FasL expression of diaphragmatic muscle cells were examined by the streptavidin biotin-peroxidase complex (SABC) immunohistochemistry techniques and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and Dunnett-t test was employed to compare the effects of SMI and aminophylline. RESULTS: (1) Fas, FasL expression in normal diaphragmatic muscle cells was very low with a positive rate of (2.77 +/- 0.45)% and (2.32 +/- 0.61)%. After hypoxia, the positive rates increased with the time of hypoxia time. SMI showed an inhibition on diaphragmatic muscle cell Fas and FasL expression;after hypoxia 1 w, 2 w, 3 w and 4 w, Fas expression [(6.36 +/- 4.17)%, (9.77 +/- 4.12)%, (18.02 +/- 6.91)% and (21.09 +/- 8.09)%] and FasL expression [(5.32 +/- 6.16)%, (9.58 +/- 3.79)%, (12.01 +/- 8.71)%, (19.43 +/- 10.31)%] in B group were different from those in A group respectively (all P < 0.05). But aminophylline did not show such an effect, the expression of Fas [(10.87 +/- 3.62)%, (24.13 +/- 3.79)%, (35.39 +/- 9.02)%, (39.56 +/- 10.12)%] and FasL [(9.37 +/- 4.07)%, (20.16 +/- 4.88)%, (31.81 +/- 7.07)%, (35.51 +/- 9.13)%] were not significantly different from those in A group respectively (all P > 0.05). (2) Diaphragmatic muscle cell apoptosis was very low in normal rats with a rate of (0.93 +/- 0.29)%, which also increased after hypoxia and the increase was associated with the time of hypoxia. Apoptosis rate was decreased by the administration of SMI, the rates of B group were (5.01 +/- 3.71)%, (9.37 +/- 3.12)%, (14.66 +/- 8.76)%, (18.16 +/- 7.02)%, respectively. Except for the first week, the differences of other weeks were all statistically significant when compared with A groups (all P < 0.05). But the effect of aminophylline was different, as compared to A group, only the apoptosis rate in hypoxia 4 w [(30.92 +/- 11.13)%] of C group being statistically significant different (P < 0.05). CONCLUSIONS: Fas and FasL participated in diaphragmatic muscle cell apoptosis in rats with chronic hypoxia. SMI showed a definite effect on the Fas and FasL protein expression and decreased diaphragmatic muscle cell apoptosis, which contributed to the therapeutic effect on diaphragmatic fatigue caused by hypoxia.