Spinal microglial M1 polarization contributes paclitaxel-induced neuropathic pain by triggering cells necroptosis.

Paclitaxel (PTX) is a chemotherapeutic agent that is widely used for the treatment of several types of tumors. However, PTX-induced peripheral neuropathy (PIPN) is an adverse effect generally induced by long-term PTX use that significantly impairs the quality of life. Necroptosis has been implicated in various neurodegenerative disorders. Necroptosis of dorsal root ganglion neurons triggers the pathogenesis of PIPN. Therefore, the present study aims to investigate the role of spinal neuronal necroptosis in PIPN. It also explores the potential role of microglial polarization in necroptosis. We established rat models of PIPN via quartic PTX administration on alternate days (accumulated dose: 8 mg/kg). PTX induced obvious neuronal necroptosis and upregulated the expression of receptor-interacting protein kinase (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the spinal dorsal horn. These effects were inhibited with a necroptosis pathway inhibitor, necrostatin-1 (Nec-1). The effect of microglial polarization on the regulation of spinal necroptosis was elucidated by administering minocycline to inhibit PTX-induced M1 polarization of spinal microglia caused by PTX. We observed a significant inhibitory effect of minocycline on PTX-induced necroptosis in spinal cord cells, based on the downregulation of RIP3 and MLKL expression, and suppression of tumor necrosis factor-α and IL-ß synthesis. Additionally, minocycline improved hyperalgesia symptoms in PIPN rats. Overall, this study suggests that PTX-induced polarization of spinal microglia leads to RIP3/MLKL-regulated necroptosis, resulting in PIPN. These findings suggest a potential target for the prevention and treatment of neuropathic pain.

Research on sweat metabolomics of athlete's fatigue induced by high intensity interval training.

Objective: Sweat is an important specimen of human metabolism, which can simply and non-invasively monitor the metabolic state of the body, and its metabolites can be used as biomarkers for disease diagnosis, while the changes of sweat metabolites before and after exercise-induced fatigue are still unclear. Methods: In this experiment, high-performance chemical isotope labeling liquid chromatography-mass spectrometry (LC-MS) was used to metabolomic 28 sweat samples before and after exercise-induced fatigue of 14 long-distance runners, also IsoMS PRO and SPSS22.0 software were used to analyze the metabolite changes and differential metabolic pathways. Results: A total of 446 metabolites with high confidence were identified, and the sweat metabolome group before and after high-intensity interval exercise-induced fatigue was obvious, among which the upregulated differential metabolites mainly included hypoxanthine, pyruvate, several amino acids, etc., while the downregulated differential metabolites mainly included amino acid derivatives, vitamin B6, theophylline, etc. Conclusion: The change of hypoxanthine concentration in sweat can be used as a good biomarker for the diagnosis of exercise-induced fatigue, while the change of pyruvate content in sweat can be used as a discriminant index for the energy metabolism mode of the body before and after exercise. The main metabolic pathways involved in differential metabolites produced before and after HIIT exercise-induced fatigue are purine metabolism and amino acid metabolism.

Research on effect of pulsatile external auditory canal irrigation on foreign bodies in children / 中国实用护理杂志

Objective:To explore the methods to improve the success rate of external canal foreign body washing and reduce the incidence of adverse reaction in children (≤14 years old).Methods:This study was a randomized controlled trial. A total of 60 pediatric patients with ear canal foreign bodies who were admitted to the otolaryngology-head and neck surgery clinic of Shengjing Hospital Affiliated to China Medical University from January 2021 to May 2022 were selected. The patients were divided into the experimental group and the control group by the random number table method, with 30 cases in each group. The experimental group were treated with pulsatile external auditory canal irrigation method, while the control group were treated with the conventional ear canal flushing method. The success rate of flushing, the flushing time, the incidence of adverse reactions and satisfaction of the patient's family were compared between the two groups.Results:The success rate of flushing was 80.0% (24/30) in the experimental group and 46.7% (14/30) in the control group, with statistically significant difference ( χ2= 7.18, P <0.05). The flushing time was (140.80 ± 44.48) s in the experimental group and (296.60 ± 82.79) s in the control group, with statistically significant difference ( t=9.08, P <0.05). The incidence of adverse reactions was 23.3% (7/30) in the experimental group and 63.3% (19/30) in the control group, with statistically significant difference ( χ2=9.77, P<0.05). The satisfaction of the patient's family was 93.9% (28/30) in the experimental group and 36.7% (11/30) in the control group, with statistically significant difference ( χ2=21.17, P<0.05). Conclusions:The pulsatile external auditory canal irrigation method can improve the success rate of ear canal foreign body flushing, shorten the flushing time and reduce the adverse reactions. The need for surgery and hospitalization due to ear canal foreign body, the suffering of patients and the corresponding cost can be decreased accordingly. The new treatment showed clear advantages clinically and should be widely applied.

Effect of salidroside on choroidal thickness and expression of hypoxia-inducible factor-1α, dopamine and its receptor in guinea pigs with myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To examine the effects of salidroside on choroidal thickness, hypoxia-inducible factor-1α(HIF-1α), dopamine(DA)and its D1 receptor expression in guinea pigs with lens-induced myopia(LIM).METHODS: A total of 18 two-week-old guinea pigs were randomly divided into the normal control(NC)group, the LIM group, and the LIM + salidroside(LIM+SA)group, with 6 guinea pigs in each group. The guinea pigs in the NC group were fed normally and intragastrically administered with 2 mL/d saline; those in the LIM group wore a -5D lens in front of their right eyes to establish a myopia model, then they were intragastrically administered with 2 mL/d saline. Finally, those in the LIM+SA group wore glasses along with intragastric administration of 2 mL/d salidroside at a dose of 100 mg/kg. The refraction, axial length, and choroidal thickness of guinea pigs in each group were measured 4wk following the establishment of the model. In addition, the relative mRNA expression and protein content of HIF-1α in the choroid and retina of guinea pigs in each group were detected by real-time quantitative PCR(qPCR)and immunohistochemistry(IHC). Finally, the DA concentration and its D1 receptor expression were detected by enzyme-linked immunosorbent assay(ELISA)and Western blot.RESULTS: At 4wk after model establishment, guinea pigs of LIM group and LIM+SA group exhibited increased negative refraction of the right eye, prolonged axial length, and decreased choroidal thickness compared to the NC group. The relative mRNA expression and protein content of HIF-1α in the choroid and retina of the guinea pigs increased. The concentration of DA and the expression of its D1 receptor both decreased. Moreover, compared to the LIM group, the diopter of the right eye of guinea pigs in LIM+SA group significantly reduced, the axial length was shorter, the thickness of choroid increased, the relative mRNA expression and protein content of HIF-1α in the choroid and retina decreased and the concentration of DA and the expression of its D1 receptor both increased.CONCLUSION: Salidroside can delay myopia progression in myopic guinea pigs by affecting choroidal thickness and the expression of HIF-1α, DA and its D1 receptor.

Right-to-Left Displacement of an Airgun Lead Bullet after Transorbital Entry into the Skull Complicated by Posttraumatic Epilepsy : A Case Report

Penetrating head injury is a serious open cranial injury. In civilians, it is often caused by non-missile, low velocity flying objects that penetrate the skull through a weak cranial structure, forming intracranial foreign bodies. The intracranial foreign body can be displaced due to its special quality, shape, and location. In this paper, we report a rare case of right-to-left displacement of an airgun lead bullet after transorbital entry into the skull complicated by posttraumatic epilepsy, as a reminder to colleagues that intracranial metal foreign bodies maybe displaced intraoperatively. In addition, we have found that the presence of intracranial metallic foreign bodies may be a factor for the posttraumatic epilepsy, and their timely removal appears to be beneficial for epilepsy control.

Effects and mechanisms of curcumin on apoptosis of retinal ganglion cells in chronic ocular hypertension rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the effects and mechanisms of curcumin on apoptosis of retinal ganglion cells(RGCs)in chronic ocular hypertension rats.METHODS:A total of 21 Spraque-Dawley(SD)rats were randomly divided into 3 groups with 7 rats in each group. The rat models of chronic ocular hypertension were established by cauterization of the superior scleral veins in the high intraocular pressure model group and the curcumin treatment group, and the sham operation group only cut the conjunctiva without the cauterization of the superior scleral veins; the rats in the curcumin treatment group were intragastrically treated with curcumin at a dose of 4mL/kg, and the rats in the sham operation group and the high intraocular pressure model group were treated with pure water at a dose of 4mL/kg for 3wk. After 3wk, HE staining was used to observe the morphological and pathological changes of retina, the number of RGCs and the thickness of ganglion cell layer(GCL)in each group of rats; TUNEL staining was used to observe the apoptosis of RGCs and retinal cells in each group of rats; the expression levels of glutamate-cysteine ligase modifier subunit(GCLM)and heme oxygenase-1(HO-1)in the retina of each group of rats were detected by real-time fluorescence quantitative PCR, immunohistochemical staining and Western blot.RESULTS:Compared with the sham operation group, the retinal morphology of rats in the high intraocular pressure model group and the curcumin treatment group was disorganized, the number of RGCs was reduced, the GCL was thinner, the apoptosis rate of RGCs and retinal cells increased, and the expression levels of GCLM and HO-1 increased. Compared with the high intraocular pressure model group, the retinal morphology of rats in the curcumin treatment group was basically normal, the number of RGCs increased, the GCL thickened, the apoptosis rate of RGCs and retinal cells decreased, and the expression levels of GCLM and HO-1 increased.CONCLUSION:Curcumin can inhibit the apoptosis of RGCs in the rat model of chronic ocular hypertension by up-regulating the expression of antioxidant genes GCLM and HO-1.

Relationship between postoperative delirium and preoperative frailty in elderly patients undergoing spinal surgery / 中华麻醉学杂志

Objective:To evaluate the relationship between postoperative delirium(POD) and preoperative frailty in elderly patients undergoing spinal surgery.Methods:Two hundred and twenty patients of both sexes, aged ≥65 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ-Ⅳ, undergoing elective posterior lumbar decompression, bone grafting and internal fixation under general anesthesia, were selected. Frailty was measured using the FRAIL (fatigue, resistance, ambulation, illness, and loss of weight) scale on 1 day before surgery. POD was assessed twice a day within 3 days by Confusion Assessment Method. Patients were divided into POD group and non-POD group according to whether POD occurred within 3 days after surgery. Multivariate logistic regression analysis was used to identify the risk factors for POD in elderly patients undergoing spinal surgery, and the value of preoperative frailty in predicting POD was analyzed using the receiver operating characteristic curve.Results:A total of 190 patients were finally enrolled, among which 55 patients presented with frailty before surgery, and the incidence was 29.0%. Forty-six patients developed POD, and the incidence was 24.2%. Multivariate logistic regression analysis showed that aging ( OR=1.15, 95% confidence interval [ CI] 1.03-1.29, P=0.017), preoperative frailty ( OR=2.35, 95% CI 1.24-4.43, P=0.009), increase in surgical segments ( OR=4.14, 95% CI 1.71-10.05, P=0.002) and increase in postoperative 24-h pain VAS score ( OR=1.38, 95% CI 1.07-1.78, P=0.013) were independent risk factors for POD in elderly patients undergoing spinal surgery. The area under receiver operating characteristic curve of preoperative frailty in predicting POD was 0.702 (95% CI 0.608-0.796, P<0.001). Conclusions:Preoperative frailty is an independent risk factor for POD in elderly patients undergoing spinal surgery. Preoperative frailty can predict the occurrence of POD in elderly patients undergoing spinal surgery to some extent.

Effect of esketamine on extremity ischemia-reperfusion-induced lung injury in elderly patients undergoing total knee replacement / 中华麻醉学杂志

Objective:To evaluate the effect of esketamine on extremity ischemia-reperfusion-induced lung injury in elderly patients undergoing total knee replacement.Methods:Sixty elderly patients of both sexes, aged 65-80 yr, with body mass index <35 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective unilateral total knee replacement under neuraxial anesthesia, were divided into 2 groups according to the random number table method: control group (C group) and esketamine group (S group), with 30 cases in each group. Esketamine 0.3 mg/kg was intravenously infused before tourniquet inflation in group S. Immediately after the end of operation, the two groups received adductor block with 0.5% ropivacaine 15 ml under ultrasound guidance. And then patient-controlled intravenous analgesia was performed, patient-controlled intravenous analgesia solution included sufentanil 1.5 μg/kg in 100 ml of normal saline in group C and sufentanil 1.5 μg/kg and esketamine 0.75 mg/kg in 100 ml of normal saline in group S. The background infusion rate was 1.5 ml/h, the patient-controlled analgesia dose was 1.5 ml, and the lockout interval was 15 min in the two groups. When the visual analogue scale score at rest≥ 4 points within 3 days after surgery, ketorolac tromethamine 30 mg was intravenously injected for rescue analgesia. Blood samples from the radial artery were collected for blood gas analysis at 30 min before tourniquet inflation(T 0), 30 min after tourniquet inflation(T 1), and 3 min, 30 min and 24 h (T 4) after tourniquet release (T 2-4), and PaO 2 and PaCO 2 were recorded. The alveola-arterial oxygen partial pressure difference, oxygenation index and respiratory index were calculated. Peripheral venous blood samples were collected at T 0, T 3 and T 4 for determination of serum endothelin-1 and malondialdehyde by enzyme-linked immunosorbent assay. The requirement for rescue analgesia and occurrence of dizziness, hallucinations and pulmonary complications within 3 days after surgery were recorded. Results:Compared with group C, alveola-arterial oxygen partial pressure difference was significantly decreased at T 1-3, respiratory index was decreased, oxygenation index was increased at T 2, 3, and serum endothelin-1 and malondialdehyde concentrations were decreased at T 3, 4, and the rate of postoperative rescue analgesia was decreased in group S( P<0.05). There was no significant difference in the incidence of postoperative dizziness, hallucinations, and pulmonary complications between the two groups ( P>0.05). Conclusions:Esketamine can reduce extremity ischemia-reperfusion-induced lung injury in elderly patients undergoing total knee replacement, and the mechanism may be related to regulating vascular endothelial function and reducing lipid peroxidation.

Demand and supply of community-based care services for the elderly in China and its influencing factors / 中华老年医学杂志

Objective:To explore the demand and actual supply of community-based care services for the elderly residents and the factors that affecting care mode for them in the context of rapid urbanization and population aging in China.Methods:Based on the cross-sectional data of the seventh China Longitudinal Survey on Health and Longevity(CLHLS)(2018), 15 854 elderly residents aged 60 and above were selected as the research population.Logistic regression method was used to analyze the patterns of community-based care services and their influencing factors.Results:Among 15 854 elderly residents, 6 912(43.60%)were male and 8 942(56.40%)were female.The results of activities of daily living(ADL)evaluation showed that 11 109 elderly residents could take care of themselves completely, and 3 889 elderly residents were disabled.The disability rate was 25.93%.The proportion of social services that elderly town dwellers expect the community to provide is higher than those living in cities and rural areas in terms of daily care, spiritual care, providing health care knowledge, and dealing with neighborhood disputes.From the perspective of social services actually provided by the community, in addition to providing home-based care, the proportion of community services available to the elderly living in towns and rural areas are similar, but significantly lower than the proportion of social services provided for elderly city dwellers.Age, marital status, residence, cultural differences, health status, source of life and living preference had significant impacts on the choice of care demand patterns.Those of older age( OR=2.29, 95% CI: 1.04-5.03 for 70-79 years old; OR=2.94, 95% CI: 1.38-6.25 for elderly 80 years old or above), having no spouse( OR=3.50, 95% CI: 2.49-4.92), and with higher levels of disability( OR=4.24, 95% CI: 3.12-5.77 for mild disability; OR=7.54, 95% CI: 5.19-10.95 for moderate disability; OR=10.50, 95% CI: 7.59-14.53 for severe disability)are more inclined to choose socialized care. Conclusions:In the process of rapid urbanization in China, the demands for care services of elderly living in towns has increased, but the actual care services provided for them by the communities are yet to be improved.Moreover, elderly town dwellers are still inclined to family care, the same as those of elderly rural dwellers.

Effects of ganoderma triterpenoids combined with exogenous GM1 on cognitive function and hippocampal synaptic structure in rats with epilepsy / 中华行为医学与脑科学杂志

Objective:To study the intervention effect of ganoderma triterpenoids combined with exogenous monosialotetrahexosyl ganglioside(GM1) on cognitive dysfunction and synaptic ultrastructure of hippocampal neurons in rats with epilepsy caused by pentylenetetrazol(PTZ).Methods:A total of 40 Sprague-Dawley rats were divided into blank control group, epileptic model group, ganoderma triterpenoids group, GM1 group and GM1 combined with ganoderma triterpenoids group according to the random number table method( n=8 in each group). The rats were intraperitoneally injected with PTZ subconvulsant dose (35 mg·kg -1·d -1) once a day for 28 days to replicate the models of chronic epilepsy. And the rats in different medication groups were given corresponding administration based on daily intraperitoneal injection of PTZ(GM1: intraperitoneal injection of 30 mg·kg -1·d -1, ganoderma triterpenoids: gavage 1 000 mg·kg -1·d -1). Morris water maze was used to test the spatial exploration and learning and memory ability of epileptic rats.Transmission electron microscopy was used to observe the ultrastructure of hippocampal neurons in epileptic rats.Immunofluorescence staining was used to observe expression levels of cofilin and SYN protein in hippocampus CA1 of rats. In addition, Western blot was used to detect the expression levels of cofilin, p-cofilin and synaptophysin(SYN) protein in hippocampus of rats. SPSS 17.0 software was used for statistical analysis. Repeated one-way ANOVA was used for comparing among groups, LSD test was used for pairwise comparisons. Results:Morris water maze results showed that there were statistically significant differences in escape latency, times of crossing the platform and time spent in the target quadrant among the groups( F=5.259, 8.240, 5.961, all P<0.05). Compared with the epilepsy model group, the escape latencies((20.31±7.39) s, (21.81±6.05) s, (17.66±4.76) s) of the ganoderma triterpenoids group, GM1 group and GM1 combined with ganoderma triterpenoids group were shorter (all P<0.05), the numbers of crossing the platform ((4.63±1.41) times, (4.50±1.93) times, (5.50±1.77) times) were more (all P<0.05), the residence time in target quadrant ((31.91±5.00) s, (30.49±5.72) s, (35.70±5.34) s) were longer (all P<0.05). And the most obvious change was found in the GM1 combined with ganoderma triterpenoids group ( P<0.01). The results of transmission electron microscope showed that there were significant differences in the numbers of hippocampal neurons synapses, the synaptic gap, the density of postsynaptic membrane and length of active area of postsynaptic membrane among the groups( F=3.693, 7.201, 5.012, 4.033, all P<0.05). Compared with the epilepsy model group, the numbers of synapses ((8.00±1.79), (7.83±1.84), (8.50±1.87)) in the ganoderma triterpenoids group, GM1 group and GM1 combined with ganoderma triterpenoids group were all more (all P<0.05), synaptic gap ((33.83±3.81)nm, (32.43±4.14)nm, (30.23±3.08)nm)were narrower, and the postsynaptic dense substances ((57.50±6.03)nm, (58.10±2.40)nm, (60.73±3.81)nm) were all thicker (all P<0.05). The length of active region of postsynaptic membrane ((271.66±11.80) nm, (279.06±13.58) nm) in ganoderma triterpenoid group and GM1 combined with ganoderma triterpenoids group were longer than that in epilepsy model group (both P<0.05). Immunofluorescence results showed that the average fluorescence intensity of cofilin in the epilepsy model group was higher than that in the blank control group, and the average fluorescence intensity of SYN was lower than that in the blank control group (both P<0.05). The average fluorescence intensity of cofilin in GM1 group and GM1 combined with ganoderma triterpenoids group were lower than that in epilepsy model group (both P<0.05), and the average fluorescence intensity of SYN in ganoderma lucidum triterpenoids combined with GM1 group was higher than that in epilepsy model group ( P<0.05). Western blot showed that the expression levels of cofilin protein in the epilepsy model group was higher than that in the blank control group ((1.454±0.080), (1.092±0.099), P<0.05), and the expression of p-cofilin and SYN were lower than those in the blank control group ((1.103±0.120) vs (1.420±0.934), (1.650±0.062) vs (1.958±0.062), both P<0.05). The expression of cofilin protein ((1.227±0.071), (1.262±0.078), (1.162±0.129), P<0.05) in ganoderma triterpenoids group, GM1 group and GM1 combined with ganoderma triterpenoids group were lower than that in epilepsy model group, and the expression levels of p-cofilin(1.357±0.199) and SYN protein(1.873±0.010) in ganoderma triterpenoids combined with GM1 group were higher than that in epilepsy model group (both P<0.05). Compared with ganoderma lucidum triterpenoids group and GM1 group, there was no significant difference in each index of GM1 combined with ganoderma triterpenoids group (all P>0.05). Conclusion:GM1 combined with ganoderma triterpenoids may promote the synaptic plasticity of neurons, improve the learning and memory ability of epileptic rats.Combination medication is better than single medication in some observed indicators.

Factors affecting the elevation of inter-arm systolic blood pressure difference in a physical examination population / 中华健康管理学杂志

Objective:To analyze the related factors affecting the inter-arm systolic blood pressure difference (IASBPD) in a physical examination population.Methods:A total of 3 600 adults who underwent physical examination and completed the arteriosclerosis test in the first affiliated hospital of Anhui medical university from January 2019 to June 2021 were selected as the participants by systematic sampling method. Data on age, sex, and history of smoking, heavy drinking, hypertension, type 2 diabetes, and coronary heart disease were recorded. The height, weight, waist circumference, hip circumference, total muscle, total fat and body fat ratio were measured, and body mass index was calculated. The blood pressure of the limbs, ankle brachial index (ABI) were measured synchronously with the arteriosclerosis tester of the Chinese Academy of Sciences, and the IASBPD were calculated. According to the IASBPD value, the participants were divided into two groups: IASBPD<10 mmHg (1 mmHg=0.133 kPa) group and IASBPD≥10 mmHg group, The differences between the two groups were compared, and the related influencing factors of IASBPD were analyzed by multivariate logistic regression.Results:Weight, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, total muscle, total fat, body fat rate, history of hypertension, proportion of type 2 diabetes mellitus, and proportion of history of coronary heart disease in the IASBPD≥10 mmHg group was higher than that of IASBPD<10 mmHg group [(69.1±11.2) vs (65.3±10.8) kg, (25.6±3.4) vs (24.4±3.3) kg/m 2, (91.3±11.3) vs (87.8±10.6) cm, (98.5±10.4) vs (96.5±9.8) cm, (139.7±20.0) vs (129.7±17.6) mmHg, (80.3±11.6) vs (76.7±10.1) mmHg, (47.5±9.1) vs (45.3±8.8) kg, (19.4±7.0) vs (17.6±6.4) kg, (27.9%±8.5%) vs (26.8%±8.1%), 41.1% vs 29.3%, 16.6% vs 11.7%, 13.1% vs 7.3%] (all P<0.05); ABI was lower than that in IASBPD<10 mmHg group [(1.15±0.11) vs (1.20±0.09)] ( P<0.001). There were no significant differences in height, smoking history and heavy drinking history between the two groups (all P>0.05). Multivariate logistic regression analysis showed that age, systolic blood pressure, body weight and ABI were independent influencing factors of IASBPD≥10 mmHg. Age, systolic blood pressure and body weight were positively correlated with IASBPD≥10 mmHg, while ABI was negatively correlated with IASBPD≥10 mmHg. Conclusion:Increases in age, systolic blood pressure, and body weight and a decrease in ABI are important influencing factors leading to the elevation of IASBPD.

Macrophage Polarization and Anti-tumor Mechanism of Chinese Medicine：A Review / 中国实验方剂学杂志

Macrophages are natural immune cells with strong plasticity. The polarization of macrophages mainly responds to stimuli in the microenvironment by changing their phenotype and related functions. In recent years， studies have found that the polarization of macrophages is involved in the occurrence and development of various diseases such as bone arthritis， skin diseases， diabetes， coronary heart disease， breast cancer， colorectal cancer， and lung cancer， especially the metastasis of malignancies and drug resistance， through multiple signaling pathways， including nuclear factor kappa-B（NF-κB）， c-Jun N-terminal kinase（JNK）， protein kinase B （Akt）， mitogen-activated protein kinase （MAPK）， signal transducer and activator of transcription 6 （STAT6）， Wnt/β-catenin， and mammalian target of rapamycin （mTOR） and regulatory factors， such as granulocyte-macrophage colony-stimulating factor （GM-CSF）， interleukin （IL）-4， IL-10， transforming growth factor （TGF）-β， tumor necrosis factor（TNF）-α， and interferon-γ（IFN-γ）. Chinese medicine is also pivotal in the prevention and treatment of malignancies. In recent years， therefore， the specific anti-tumor mechanism of Chinese medicine and its active ingredients has become a research hotspot. The tumor microenvironment is crucial to the occurrence and development of tumors. The polarization of tumor-associated macrophages is involved in the proliferation， apoptosis， and metastasis of tumor cells. Therefore， targeted regulation of the polarization of tumor-associated macrophages is a potential target for clinical treatment of malignancies. Based on the research articles published in the past three years， this article reviewed macrophage polarization and the anti-tumor mechanism of Chinese medicine from four perspectives， i.e.， macrophage polarization， related pathways and regulatory factors of macrophage polarization， macrophage polarization and breast cancer， colorectal cancer， and lung cancer， and macrophage polarization and anti-tumor effects of Chinese medicine， active ingredients of Chinese medicine， and self-formulated prescriptions/classic prescriptions. This study is expected to provide certain ideas for the clinical treatment， basic research， and development of new Chinese medicine in the treatment of tumors.

Mechanical stress and melanoma: a retrospective analysis of 129 cases of plantar melanoma / 中华皮肤科杂志

Objective:To analyze potential roles of mechanical stress in the formation of plantar melanoma.Methods:A retrospective analysis was conducted on 129 cases of plantar melanoma in Xiangya Hospital, Central South University between 2014 and 2021, and the distribution and clinical characteristics of plantar melanoma were analyzed. The goodness-of-fit test was used to compare the distribution of plantar melanoma between weight-bearing areas (the toes, forefoot, lateral midfoot, heel) and non-weight-bearing areas of the foot (the arch) , while t test, Fisher′s exact test and Wilcoxon rank sum test were used to analyze differences in clinicopathological characteristics of plantar melanoma between weight-bearing areas and non-weight-bearing areas of the foot. Results:Among the 129 patients with plantar melanoma, 66 (51.2%) were males and 63 (48.8%) were females, and their age at onset was 60.6 ± 13.1 years. Plantar melanoma mostly occurred on the heel (65 lesions, 1.31 lesions per square centimeter) , followed by the forefoot (31 lesions, 0.41 lesions per square centimeter) , the bottom of the toes (15 lesions, 0.43 lesions per square centimeter) , lateral midfoot (11 lesions, 0.38 lesions per square centimeter) and the arch of foot (7 lesions, 0.16 lesions per square centimeter) . The goodness-of-fit test showed that melanoma was more prone to occur in the weight-bearing areas than in the non-weight-bearing areas ( χ2 = 66.59, P < 0.001) ; compared with the arch of foot, a higher incidence density was observed in the heel and forefoot ( χ2 = 38.29, 5.23, P < 0.001, = 0.022, respectively) . There were no significant differences in the gender ratio, age and occupation of patients, prevalence rates of left/right foot involvement, Breslow thickness, ulceration status, Clark grades, lymph node metastasis rate, and stages between melanomas in the weight-bearing areas and those in non-weight-bearing areas (all P > 0.05) . Conclusion:Plantar melanoma was more prone to occur in the weight-bearing areas than in the non-weight-bearing areas, suggesting that mechanical stress may be related to the occurrence and development of melanoma.

HIF / 中南大学学报(医学版)

OBJECTIVES@#To analyze the expressions and distributions of hypoxia-inducible factor-1α (HIF-1α), CD147, and glucose transporter 1 (GLUT1) in epidermis from psoriasis vulgaris and normal people, and to explore the associations among these proteins and their roles in hypoxic HaCaT cell line.@*METHODS@#The expression levels of HIF-1α, CD147, and GLUT1 were determined by immunohistochemistry staining in skin biopsies from 48 psoriasis vularis patients and 33 healthy subjects. Cobalt chloride (CoCl@*RESULTS@#HIF-1α, CD147, and GLUT1 were highly expressed and the glycolytic capacity was increased in lesions of psoriasis vulgaris; HIF-1α upregulated the expression of CD147 and GLUT1, increased the lactate production and decreased the ATP level in CoCl@*CONCLUSIONS@#Glycolytic capacity increases in the injured keratinocytes of psoriasis vulgaris, suggesting that HIF-1α, CD147, and GLUT1 are associated with glycolysis, which can be considered as the promising targets for psoriasis therapy.

Predictive value of visceral fat area for multiple metabolic risk factors in obese patients undergoing bariatric surgery / 中华消化外科杂志

Objective:To investigate the predictive value of visceral fat area (VFA) on multiple metabolic risk factors in obese patients undergoing bariatric surgery.Methods:The retrospective case-control study was conducted. The clinical data of 146 obese patients undergoing bariatric surgery in the West China Hospital of Sichuan University from June 2015 to May 2020 were collected. There were 57 males and 89 females, aged (33±9)years, with a range from 15 to 65 years. All patients underwent multi-slice spiral computed tomography (CT) examination, and the total fat area (TFA), VFA and subcutaneous fat area (SFA) were measured. Observation indicators: (1) CT findings of abdominal fat area and patients with multiple metabolic risk factors; (2) receiver operator characteristic(ROC) curve of different clinical indicators for predicting multiple metabolic risk factors; (3) relationship between different VFA and clinicopathological features in patients; (4) analysis of factors influencing multiple metabolic risk factors in patients. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was analyzed by independent sample t test. Measurement data with skewed distribution were expressed as M (range) and comparison between groups was analyzed by nonparametric rank sum test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test. The ROC curve was used to analyze the predictive value of different clinical indicators for multiple metabolic risk factors in patients. Logistic regression analysis was used for univariate and multivariate analysis. Results:(1) CT findings of abdominal fat area and patients with multiple metabolic risk factors. CT findings of 146 patients showed that VFA was (212±122)cm 2, SFA was (419±147)cm 2, visceral-to-subcutaneous fat ratio (VSR) was 0.60±0.54. The levels of systolic blood pressure (SBP), diastolic blood pressure, fasting blood glucose (FBG), triglyceride and highdensity lipoprotein cholesterol (HDL-C) were (131±16)mmHg(1 mmHg=0.133 kPa), (86±12)mmHg, (6.4±2.5)mmol / L, 4.43 mmol /L(range, 1.23-9.99 mmol/L), (1.5±1.3)mmol/L, respectively. Among the 146 patients, 85 had impaired FBG or diabetes, 82 had hypertension, 139 had high triglyceride, 91 had low serum HDL-C; 128 had multiple metabolic risk factors. (2) ROC curve analysis of different clinical indicators for predicting multiple metabolic risk factors: the ROC curve showed that VFA had better ability to predict or diagnose multiple metabolic risk factors in patients ( hazard ratio=0.617, 95% confidence interval as 0.470-0.764, P<0.05). The cutoff value of VFA was 163.52 cm 2 by calculating Yoden index in ROC curve. (3) Relationship between different VFA and clinicopathological features in patients: according to the cutoff value of 163.52 cm 2 in ROC curve, 146 patients were divided into high VFA group (≥163.52 cm 2) and the low VFA group (<163.52 cm 2), with 49 cases and 97 cases respectively. Cases with hypertension, level of SBP, cases with impaired FBG or diabetes, cases with multiple metabolic risk factors were 64, (134±17)mmHg, 63, 90 for the high VFA group, versus 18, (127±13)mmHg, 22, 38 for the low VFA group; there were significant differences in above indicators between the two groups ( χ2=11.309, t=6.916, χ2=5.380, 6.988, P<0.05). (4) Analysis of factors influencing multiple metabolic risk factors in patients: results of univariate analysis showed that VFA was a related factor for multiple metabolic risk factors in patients ( hazard ratio=3.722, 95% confidence interval as 1.341-10.328, P<0.05). Results of multivariate analysis showed that the VFA≥163.52 cm 2 was an independent rsik factcor or multiple metabolic risk factors in patients ( hazard ratio=5.182, 95% confidence interval as 1.441-18.641, P<0.05). Conclusions:VFA is positively correlated with hypertension, systolic blood pressure, impaired FBG and diabetes. VFA≥163.52 cm 2 is an independent predictor for multiple metabolic risk factors in obese patients undergoing bariatric surgery.

Syndrome Differentiation of Chinese Medicine in Mars 500 Long-Term Closed Environment / 中国结合医学杂志

OBJECTIVE@#To summarize and elucidate the characteristics and evolvement of Chinese medicine (CM) patterns reflecting the physical and mental conditions of participants in the Mars 500 long-term closed environment.@*METHODS@#The DS01-T Digital TCM Four-Diagnostic Instrument and CM Inquiring Diagnostic Questionnaire were used to collect information from 6 participants in the Mars 500 International Joint Research Project, through diagnostic methods of observation, palpation and inquiry according to CM theory. During the 520 days of the experiment, data collection was performed 37 times; a total of over 400 digital images of tongues and facial complexion and over 20,000 data were collected. These data were then analyzed by a team of experts in CM, statistics, and data mining.@*RESULTS@#The CM pattern evolvement of participants in the long-term closed environment followed some common trends. Qi deficiency was the main CM pattern observed, with individual features depending on constitutional differences [manifested in varying degrees of accompanying patterns of Gan (Liver) qi stagnation, Pi (Spleen) deficiency, dampness encumbering, or yin deficiency].@*CONCLUSION@#The research has verified the effectiveness of CM syndrome differentiation based on the four diagnostic methods, which should serve as a solid foundation for observation, monitoring, and intervention in regard to the health conditions of astronauts in long-term space flights in the future.

Inhibitory Effect of Essential Oil from Fructus Alpinia zerumbet on Endothelial-to-mesenchymal Transition Induced by High Glucose via Nrf2/Notch1 Signaling Pathway / 中国实验方剂学杂志

Objective:To investigate the inhibitory effect and the possible mechanism of essential oil from fructus Alpinia zerumbet （EOFAZ） on endothelial-to-mesenchymal transition （EndMT） induced by high glucose （HG）. Method:Human umbilical vein endothelial cells （HUVECs） was cultured in vitro to analyze the pharmacodynamic effects of EOFAZ on EndMT and oxidative stress damage induced by HG. The experiment was set the blank group， HG group （35 mmol·L-1）， EOFAZ low dose group （1 μg·L-1） and EOFAZ high dose group （4 μg·L-1）. After EOFAZ intervention for 2 h， HG was added to incubate for 72 h in order to establish EndMT cell model. Western blot was used to detect the protein expression of vimentin and platelet endothelial cell adhesion molecule （CD31）. Angiogenesis experiment was used to detect the ability of cell migration ability in order to analyze the effect of EOFAZ on EndMT. The changes of reactive oxygen species （ROS） levels were detected by 2'，7'-dichlorodihydrofluorescein diacetate （DCFH-DA） fluorescence probe and the contents of malondialdehyde （MDA）， superoxide dismutase （SOD） and catalase （CAT） in cells were detected by the kit method to analyze the effect of EOFAZ on oxidative stress. Western blot was used to detect the protein expression levels of nuclear transcription factor E2 related factor 2 （Nrf2） and Notch1. The overexpression of Nrf2 was achieved by adenovirus （AD） transfection and the mechanism of EOFAZ inhibiting EndMT was further analyzed. The experiment was set the blank group， HG group （35 mmol·L-1）， AD-Nrf2 group， EOFAZ group （4 μg·L-1）， AD-Nrf2+EOFAZ group （4 μg·L-1）. The cells were infected with recombinant adenovirus overexpression plasmid of Nrf2 gene for 6 h， then replaced with normal medium for 24 h. After EOFAZ intervention for 2 h， HG was added to co-incubate for 72 h to induce EndMT. Western blot was used to detect the protein expressions of Nrf2， CD31， vimentin， Notch1 and Snail. Result:Compared with the HG group， after treatment with EOFAZ， the protein expression of CD31 was significantly up-regulated （P<0.05）， the protein expression of vimentin was significantly down-regulated （P<0.01）， the ability of cell migration was decreased （P<0.01）， and the contents of ROS and MDA were decreased （P<0.05， P<0.01）， the levels of CAT and SOD were increased （P<0.01）. In addition， EOFAZ could significantly up-regulate the protein expression of antioxidant signal Nrf2 （P<0.01） and down-regulate the protein expression of Notch1 （P<0.01）. High expression of Nrf2 was achieved by stable AD transfection into HUVECs. The results of Western blot showed that， compared with the HG group， the protein expression levels of Nrf2 and CD31 in each treatment group were significantly increased （P<0.01）， while the protein expression levels of vimentin， Notch1 and Snail were down-regulated （P<0.01）. At the same time， compared with the AD-Nrf2 group， the AD-Nrf2+EOFAZ group could further up-regulate the protein expressions of Nrf2 and CD31 （P<0.05， P<0.01）， while decrease the protein expression levels of vimentin， Notch1 and Snail （P<0.01）. Conclusion:EOFAZ ameliorates oxidative stress injury of vascular endothelial cells induced by HG and inhibits EndMT， which is related to Nrf2/Notch1 signaling pathway.

Role of striatal HCN4 channels in striatum in paclitaxel-induced neuropathic pain in rats: its relationship with GABA B receptors / 中华麻醉学杂志

Objective:To evaluate the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in striatum in paclitaxel-induced neuropathic pain and the relationship with GABA B receptors in rats. Methods:Healthy clean-grade male Sprague-Dawley rats, aged 6-9 weeks, weighing 180-220 g, were used in this study.The neuropathic pain model was established by intraperitoneal injection of paclitaxel 2 mg/kg once every 2 days for 7 consecutive days in anesthetized rats, and then intrathecal catheterization was performed.Fifty rats in which intrathecal catheters were successfully implanted were divided into 5 groups ( n=10 each) using a random number table method: paclitaxel group (P group), paclitaxel plus normal saline group(N group), paclitaxel plus lentivirus empty vector group (BV group), paclitaxel plus HCN4 channel lentivirus group (H group), and paclitaxel plus HCN channel inhibitor ZD7288 group (I group). Ten rats of the same age were selected as the blank control group (C group). At 15 days after intraperitoneal injection of paclitaxel, normal saline 20 μl was intrathecally injected in group N, group BV received intrathecal injection of HCN4 channel lentivirus empty vector 1×10 8 TU/ml, 20 μl, group H received intrathecal injection of HCN4 channel lentivirus 1×10 8 TU/ml, 20 μl, and group I received intrathecal injection of ZD728830 μg, 20 μl.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before paclitaxel injection and 14 and 21 days after injection.The cerebral striatum tissues were obtained at T 2, and the expression of HCN4 channel and GABA B receptors was determined by immunohistochemistry and Western blot. Results:Compared with group C, the MWT was significantly decreased, HCN4 channel expression was up-regulated, and GABA B receptor expression was down-regulated in group P ( P<0.05). Compared with group P, the MWT was significantly increased, HCN4 channel expression was down-regulated, and GABA B receptor expression was up-regulated in group H and group I ( P<0.05), and no significant change was found in the parameters mentioned above in group N and group BV ( P>0.05). Conclusion:Up-regulation of expression of HCN4 channels in striatum can induce down-regulation of GABA B receptor expression, which is involved in the pathophysiological mechanism of paclitaxel-induced neuropathic pain in rats.

Effects of Ganoderma Triterpenoids on Learning and Memory Impairment in Rats with Epilepsy / 中国康复理论与实践

Objective:To study the effect of Ganoderma triterpenoids combined with exogenous monosialoteterahexosyl ganglioside (GM1) on cognitive dysfunction in rats with epilepsy. Methods:A total of 75 Sprague-Dawley rats were divided randomly into blank control group, epileptic model group, Ganoderma triterpenoids group, GM1 group and GM1 combined with Ganoderma triterpenoids group (combination group), with 15 rats in each group. All the groups, except the blank control group, were intraperitoneally injected with pentylenetetrazol (PTZ) 35 mg/kg once a day for 28 days. Medication groups were given corresponding administration based on daily intraperitoneal injection of PTZ. They were tested with Morris Water Maze; and were observed with transmission electron microscopy and HE staining for hippocampal neurons. Real-time quantitative polymerase chain reaction was used to detect the expression of actin-binding protein (Cofilin), synaptophysin (SYN) and growth-associated protein 43 (GAP-43) mRNA in hippocampus of rats. Results:Compared with the blank control group, the escape lantency prolonged in the epileptic model group in all the time points (P < 0.05). Compared with the epileptic model group, the escape lantency shortened in the treatment groups somewhen (P < 0.05). Compared with the epileptic model group, the number of crossing the platform increased in the treatment groups (P < 0.01), and the time of staying in the target quadrant prolonged (P < 0.01); while the number of pyramidal cells increased, the nuclear lysis and fragmentation reduced, the structure of neurons and the number of synapses improved， as well as the organelle structure. Compared with the blank control group, the expression of Cofilin mRNA increased (P < 0.05), and the expression of SYN mRNA and GAP-43 mRNA decreased (P < 0.05) in the epileptic model group; compared with the epileptic model group, the expression of Cofilin mRNA decreased (P < 0.05), and the expression of SYN mRNA increased (P < 0.05) in all the treatment groups, while the expression of GAP-43 mRNA increased (P < 0.05) only in the combination group. Conclusion:Ganoderma triterpenoids, GM1 and their combination can improve the learning and memory abilities of epileptic rats, which may be associated with increasing the expression of SYN and GAP-43, decreasing the expression of Cofilin, to promote the synaptic remodeling of hippocampal tissue and protect brain neurons from PTZ-induced epilepsy.

Evodiamine induces apoptosis of human hepatoma cell line BEL-7402 by Hippo-YAP pathway / 中草药

Objective: To investigate the effects and the underlying mechanisms of evodiamine (EVO) on apoptosis of hepatocellular carcinoma (HCC) BEL-7402 cells. Methods: Cell counting kit-8 (CCK-8) assay was used to detect the effect of EVO on proliferation activity of BEL-7402 cells. Hoechst 33258 staining was used for observing morphological changes of apoptosis. The cell apoptosis and cycle distribution were analyzed by flow cytometry. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assay were used to detect the expression levels of key genes from Hippo-YAP pathway in HL-7702 and BEL-7402 cells, including mammalian STE20-like protein kinase 1/2 (MST1/2), large tumor suppressor 1 (LATS1), and Yes-associated protein (YAP), then to examine the effect of EVO on the expression levels of these genes in BEL-7402 cells. The effect of EVO on the expression of YAP in hepatocellular carcinoma BEL-7402 cells was observed by immunofluorescence assay. Results: The proliferation of BEL-7402 cells were significantly inhibited by EVO in a dose- and time-dependent manners. Hoechst 33258 staining showed that EVO induced BEL-7402 cell typical apoptotic morphology, such as nuclear chromatin concentration and edge accumulation. Besides, flow cytometry tests showed that BEL-7402 cell apotosis were increased and cell cycle arrested in G2/M phase after being treated with EVO (P < 0.01). qRT-PCR and Western blotting showed that the expression level of MST2 and LATS1 were lower in BEL-7402 cell (P < 0.05), while the transcription and protein levels of YAP were significantly higher (P < 0.05). EVO could activate Hippo signal pathway, upregulate the expression of MST2 and LATS1 and then inhibit the expression of YAP in BEL-7402 cell (P < 0.05). Immunofluorescence assay also validated that EVO would significantly inhibit the overexpression of YAP in BEL-7402 cell (P < 0.01). Conclusion: EVO can induce the apoptosis of BEL-7402 cells, which may be through activating Hippo signal pathway and then down-regulate the expression of YAP.