Objective:To investigate the effects of SINC, a novel secreted protein of Chlamydia psittaci, on the apoptosis of host cells and the regulatory role of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway in it. Methods:HeLa cells were treated with recombinant SINC. The expression of Bax and Bcl-2 at protein level and the phosphorylation of ERK1/2 were analyzed by Western blot. Hoechst 33258 staining was used to detect the apoptosis of HeLa cells after SINC stimulation. Moreover, HeLa cells were pretreated with MEK1/2 inhibitor U0126 (50 μmol/L), and then stimulated with different concentrations of SINC for different time. Flow cytometry was used to detect the changes in cell apoptosis rates and Western blot was performed to detect the expression of Bax and Bcl-2 at protein level.Results:Treating HeLa cells with 10 μg/ml of SINC for 18 h resulted in down-regulated Bax and up-regulated Bcl-2 at protein level. Besides, the ratio of Bax/Bcl-2 was the lowest and a significant increase in the ratio of phosphorylated ERK1/2 (p-ERK1/2) to ERK1/2 was observed. Hoechst 33258 staining showed that the number of apoptotic bodies decreased significantly after stimulating HeLa cells with 5, 10 and 15 μg/ml of SINC. In the presence of MEK1/2 inhibitor U0126, the expression of Bcl-2 at protein level was down-regulated, while the expression of cleaved PARP was significantly up-regulated. Flow cytometry showed a significantly enhanced apoptosis of HeLa cells.Conclusions:SINC can inhibit the apoptosis of HeLa cells through activating the MAPK/ERK signaling pathway.

ObjectiveTo investigate the possible mechanisms of modified Xiaoyao Powder （逍遥散） in the treatment of hyperprolactinemia （HPRL） with liver constraint and spleen deficiency. MethodsNinety-six female SD rats were randomly divided into a normal group （n=16） and a modeling group （n=80）. In the modeling group， rats were subjected to chronic unpredictable stress combined with intraperitoneal injection of metoclopramide to establish a rat model of HPRL with liver constraint and spleen deficiency. The 80 successfully modeled rats were randomly divided into a model group， a high， medium， and low-dose group of modified Xiaoyao Powder， and a bromocriptine group， with 16 rats in each group. The high， medium， and low-dose groups of modified Xiaoyao Powder were orally administered doses of 60， 30， and 15 g/（kg·d） respectively， the bromocriptine group was orally administered bromocriptine tablets at a dose of 1 mg/（kg·d）， and the normal group and model group were orally administered 10 ml/（kg·d） of normal saline for 14 consecutive days. ELISA was used to detect serum prolactin （PRL） level； immunohistochemistry was used to determine the expression of tumor necrosis factor-alpha （TNF-α） and tyrosine hydroxylase （TH） in the hypothalamus； Western blot was used to detect the protein expression of tumor necrosis factor receptor 1 （TNFR1） in the hypothalamus； Real-time PCR was used to detect the mRNA expression of receptor interacting protein kinase 3 （RIP3） in the hypothalamus； immunofluorescence was used to detect the co-expression of RIP3 and dopamine neurons in the hypothalamus. ResultsCompared with the normal group， the serum PRL levels were increased in the model group， and the expression of hypothalamic TNF-α， TNFR1， RIP3 mRNA， and the co-expression of RIP3 with dopamine neurons were significantly increased， while TH expression was decreased （P＜0.05 or P＜0.01）. Compared with the model group， the expression of hypothalamic TNF-α was decreased in the bromocriptine group and low-dose group of modified Xiaoyao Powder， and the expression of TH was significantly increased in the medium and high-dose groups of modified Xiaoyao Powder and the bromocriptine group. The serum PRL levels， hypothalamic TNFR1 and RIP3 mRNA expression， and the co-expression of RIP3 with dopamine neurons were significantly decreased in all dose groups of modified Xiaoyao Powder and the bromocriptine group （P＜0.05 or P＜0.01）. Compared with the bromocriptine group， the serum PRL level were significantly increased in the high and low-dose groups of modified Xiaoyao Powder， TH expression was significantly increased in the medium-dose group of modified Xiaoyao Powder， hypothalamic RIP3 mRNA expression was decreased in the low-dose group of modified Xiaoyao Powder， and the co-expression of RIP3 with dopamine neurons was significantly increased in the high-dose group of modified Xiaoyao Powder （P＜0.01）. ConclusionModified Xiaoyao Powder can regulate the programmed cell death of hypothalamic dopamine neurons， affect DA expression， and regulate PRL levels， which may be one of its mechanisms in the treatment of HPRL with liver constraint and spleen deficiency.

By consulting the ancient and modern literature， the name， origin， quality evaluation， harvesting and processing methods of Curculiginis Rhizoma（CR） were systematically combed and verified， in order to provide a basis for the development and utilization of famous classical formulas containing CR. The results of herbal textual research showed that the name Xianmao was first recorded in Leigong Paozhilun， the name of CR was used in all dynasties and this name came from its efficacy and morphological characteristics， the mainstream source for CR of the past dynasties was the rhizome of Curculigo orchioides or C. capitulata， since modern times， C. orchioides has been the main source of commodities. In ancient times， most of the places of origin of the description were the western regions and southwest China， while in modern times， Sichuan and Guizhou were regarded as genuine places. Since modern times， its quality has been summarized as the best with thick roots， firm texture and black-brown surface， the harvesting and processing methods recorded in the past dynasties are mainly sun drying after harvest in the second， eighth and ninth months of the lunar calendar， and most of them are harvested in autumn and winter in modern times. In ancient times， there were many processing methods of CR， mainly in processing with rice swill， while in modern times， stir-frying with wine was the main processing method. The nature， taste， meridian tropism， functions and indications of CR are basically consistent from ancient to modern times， the taboos for taking are to avoid iron， cow's milk， and beef. Although there are some differences in the understanding of the toxicity of CR in the past dynasties， most of the materia medica are clear that it has a certain toxicity. Based on the research conclusion， it is suggested that the rhizome of C. orchioides of Lycoris family should be used as its source in the famous classical formulas， and the corresponding processing method should be selected according to the processing requirements in the formulas， while the raw products is recommended to be selected as medicine if the processing requirement is not specified.

In order to provide basic information for the utilization and development of famous classical formulas containing Bletillae Rhizoma， this article systematically analyzes the historical evolution of the name， origin， harvesting and processing of Bletillae Rhizoma by reviewing the ancient materia medica， prescription books， medical books and modern literature. The research results showed that Baiji（白及） was the main name， some scholars took Baiji（白芨） as its main name， and there were many other names such as Baiji（白给）， Baigen（白根）， Baiji（白苙）. The mainstream source of Bletillae Rhizoma was the tubers of Bletilla striata， and drying， large， white， solid， root-free and skin removed completely were the good quality standards. With the promotion of wild to cultivated medicinal materials， there were certain differences between their traits， and the quality evaluation indexes should be adjusted accordingly. The origin of records in the past dynasties was widely distributed， with Guizhou and Sichuan having high production and good quality in modern times. The harvesting period is mostly in spring and autumn， and harvested in autumn was better. The processing and processing technology is relatively simple， and it was used fresh or powdered in past dynasties， while it is mainly sliced for raw use in modern times. Based on the results， it is suggested that the tubers of Bletilla striata of Orchidaceae should be used in the famous classical formulas， and it should be uniformly written as Baiji（白及）. And if the original formula indicates the requirement of processing， it should be operated according to the requirement， if the requirement of processing is not indicated， it can be used in raw form as medicine.

Objective To investigate the effect of long noncoding RNA nuclear paraspeckle assembly transcript 1(lncRNA NEAT1)on autophagy in membranous nephropathy(MN)and its mechanism.Methods HK-2 cells were induced by albumin to construct MN model in vitro.HK-2 cells were divided into 5 groups:control group,model group,LY294002(PI3K inhibitor)group,OV-NEAT1(NEAT1 overexpression)group and OV-NEAT1+LY294002 group.Cell proliferation was detected by CCK-8.Cell apoptosis was detected by flow cytometry.Expressions of autophagy and PI3K/Akt/mTOR pathway-related mRNA and protein were detected by qRT-PCR and Western blotting.Results Compared with control group,the cell proliferation ability,LC3-Ⅱ and Beclin 1 mRNA levels as well as LC3-Ⅱ/Ⅰ and Beclin 1 protein expression levels in the model group were signifi-cantly decreased(all P＜0.01).The apoptosis rate,LC3-Ⅰ,PI3K,Akt,mTOR mRNA and p-PI3K,p-Akt,p-mTOR protein ex-pression levels were significantly increased(all P＜0.01).Compared with model group,the cell proliferation ability,LC3-Ⅱ and Beclin 1 mRNA and LC3-Ⅱ/Ⅰ and Beclin 1 protein expression levels in OV-NEAT1 group were significantly decreased(all P＜0.05).The apoptosis rate,LC3-Ⅰ,PI3K,Akt,mTOR mRNA and p-PI3K,p-Akt,p-mTOR protein expression levels were sig-nificantly increased(all P＜0.01).LY294002 group witnessed the opposite trend.Compared with LY294002 group,cell prolifer-ation ability,LC3-Ⅱ and Beclin 1 mRNA and LC3-Ⅱ/Ⅰ and Beclin 1 protein expression levels in OV-NEAT1+LY294002 group were significantly decreased(all P＜0.05).The apoptosis rate,LC3-Ⅰ,PI3K,Akt,mTOR mRNA and p-PI3K,p-Akt,p-mTOR protein expression levels were significantly increased(all P＜0.05).Conclusion lncRNA NEAT1 can inhibit albumin-induced autophagy in HK-2 cells,and the mechanism may be related to the activation of PI3K/Akt/mTOR signaling pathway.

Objective To explore the potential mechanism of Erzhi Wan in the treatment of multiple myeloma(MM)based on network pharmacology,molecular docking and cell experimental verification.Methods Network pharmacology and molecular docking were used to screen the key indicators of drugs-diseases-targets-pathways.MM line RPMI-8226 cells were cultured and given Erzhi Wan intervention.Apoptosis was detected by Annexin V-fluorescein isothiocyanate(FITC)staining.Transwell assay was used to determine cell invasion ability.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the mRNA expressions of protein kinase B(Akt),cyclin D1(CCND1),glycogen synthase kinase 3β(GSK-3β)and c-Myc.Western Blot was used to detect the protein expressions of Akt,phosphorylated protein kinase B(p-Akt),CCND1,c-Myc,GSK-3β and phosphorylated glycogen synthase kinase 3β(p-GSK-3β).Results Fourteen effective components of Erzhi Wan were obtained.There were 142 targets involved in the treatment of MM by Erzhi Wan.The results of pathway enrichment analysis showed that the key targets may be mainly concentrated in cancer pathways,lipids and atherosclerosis.Molecular docking results showed that luteolin and quercetin had good binding activity and stability with GSK-3β.Further cell experimental verification showed that compared with the blank group,the apoptosis rate of cells in the low-,medium-and high-dose groups of Erzhi Wan was significantly increased,the number of cell invasion was decreased,the mRNA and protein levels of GSK-3β were significantly increased,and the mRNA and protein levels of CCND1,Akt and c-Myc were significantly decreased in a dose-dependent manner,among them,the differences in the medium-and high-dose groups being statistically significant(P＜0.05 or P＜0.01).Conclusion The therapeutic effect of Erzhi Wan on MM may be achieved by promoting the expression of GSK-3β and inhibiting the Akt/GSK-3β/CCND1/c-Myc signaling pathway through key active components such as luteolin and quercetin.

Objective To explore the distribution patterns of tongue and pulse manifestations and traditional Chinese medicine(TCM)syndrome elements in ischemic stroke(IS)patients of different genders and ages,thus to provide approaches for the prevention and treatment of stroke with TCM.Methods The criteria of six syndrome elements in Diagnostic Scale of Syndrome Elements in Ischemic Stroke were used for the comprehensive identification of syndrome elements in 5 254 cases of inpatients confirmed as IS at the first visit in Shenzhen Traditional Chinese Medicine Hospital from 2017 to 2023.Moreover,the tongue proper,tongue coating,and whose pulse manifestations ranking in the top five in terms of the frequency of occurrence were collected for comparison and analysis.Results(1)For the distribution of TCM syndrome elements in 5 254 cases of IS patients,phlegm-dampness syndrome was the most common syndrome type(3 544 cases,67.5%),and then came qi deficiency syndrome(653 cases,12.4%)and yin deficiency syndrome(453 cases,8.6%).There were statistically significant differences in the distribution of phlegm-dampness syndrome,internal heat syndrome,and yin deficiency syndrome between the male and the female(P＜0.01).And the distribution of phlegm-dampness syndrome,qi deficiency syndrome,internal wind syndrome,and internal heat syndrome in the youth differed from that in the middle-aged and elderly(P＜0.01).(2)The tongue and pulse manifestations in IS patients with the leading six detection rates which ranked in descending order of frequency of occurrence were as follows:dull tongue(1 993 cases,37.9%),dark red tongue(1 907 cases,36.3%),thin and white coating(1 885 cases,35.9%),wiry and slippery pulse(1 714 cases,32.6%),white and greasy coating(1 679 cases,32.0%),and wiry and thready pulse(1 609 cases,30.6%).The detection rates of tongue and pulse manifestations such as light red tongue,thin and white coating in the youth group were significantly higher than those in the middle-aged and elderly group,and the detection rates of dark red tongue,and tooth-marked tongue in the middle-aged and elderly group were significantly higher than those in the youth group,the differences all being statistically significant(P＜0.05).The female patients had higher detection rates of dull tongue,thin and white coating,thin and yellow coating,wiry and thready pulse,and deep and thready pulse than male patients,while the male patients had higher detection rates of dark red tongue,red tongue,white and greasy coating,yellow and thick-greasy coating,white and thick-greasy coating,wiry and slippery pulse,and slippery pulse than the females,and the differences were all statistically significant(P＜0.05 or P＜0.01).Higher detection rate of thin and white coating was shown in the youth female than that in the youth male,while higher detection rate of wiry and slippery pulse was shown in the youth male than that in the youth female,and the differences were all statistically significant(P＜0.05 or P＜0.01).The middle-aged and elderly female patients had higher detection rates of dull tongue,thin and white coating,wiry and thready pulse,and deep and thready pulse than the middle-aged and elderly male patients,while the middle-aged and elderly male patients had higher detection rates of dark red tongue,red tongue,white and greasy coating,white and thick-greasy coating,yellow and thick-greasy coating,wiry and slippery pulse,and slippery pulse than the middle-aged and elderly female patients,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Phlegm-dampness syndrome,qi deficiency syndrome,and yin deficiency syndrome exert a significant effect on IS,and phlegm-dampness syndrome is the most common syndrome type.Factors such as gender and age have influences on the distribution of TCM syndrome in patients with IS.

Veno-arterial extracorporeal membrane oxygenation is an effective method to reduce perioperative adverse events such as cardiogenic shock in patients undergoing complex high-risk indicated percutaneous coronary intervention.Femoral artery and femoral vein are the main routes for conventional veno-arterial extracorporeal membrane oxygenation in China,while the cases of extracorporeal membrane oxygenation insertion via axillary artery are relatively rare.However,the axillary artery intubation veno-arterial extracorporeal membrane oxygenation assisted mode has been regarded as one of the routine clinical paths for the treatment of critically ill patients in foreign countries.This paper reports a case of an elderly male patient who underwent high risk and complex percutaneous coronary interventional therapy by right axillary artery implantation with extracorporeal membrane oxygenation assisted circulation due to the difficulty of femoral artery approach.In order to provide reference for the selection of clinical extracorporeal membrane oxygenation technique route.

Objective: To understand the changes in pain and its effects in patients with the diagnosis of herpes zoster. Methods: A total of 3 487 patients diagnosed with herpes zoster (HZ) for the first time at the outpatient department of Miyun District Hospital from January 1, 2017, to December 31, 2019, were included in the study. The information of patients was registered and issued with a record card. Patients were required to record the time of pain and rash by themselves. Telephone follow-up was conducted at 21, 90, 180 and 365 days after the onset of rashes, including hospitalization, location of rash and pain, and the time of start and end. The impact of pain on life was evaluated by the Zoster Brief Pain Inventory (ZBPI). Results: The age of 2 999 HZ patients included in the analysis were (53±16) years old, including 1 377 (45.91%) males and 1 903 (63.45%) patients aged 50 years and older. After 21 days of rash, mild, moderate and severe pain accounted for 20.87% (626 cases), 37.98% (1 139 cases) and 33.81% (1 014 cases), respectively. Only 5.07% (152 cases) had no pain or discomfort, and 2.27% (68 cases) had no pain but discomfort. Most of the pain sites were consistent with the rash sites. The chest and back and waist and abdomen were the most common, accounting for 35.58% (1 067 cases) and 29.18% (875 cases), respectively, followed by the limbs and face and neck, accounting for 16.74% (502 cases) and 16.40% (492 cases), respectively. The M (Q₁, Q₃) of pain days in the HZ patients was 14 (8, 20) days, and the incidence of post-herpetic neuralgia (PHN) was 6.63% (171/2 580) (excluding 419 patients who refused to visit or lost to visit on 90 days after the onset of rash). The pain score of HZ patients within 21 days after the rash was (5.19±2.73) points, and the pain score of PHN patients was (7.61±2.13) points, which was significantly higher than that of non-PHN patients [(5.04±2.69) points] (P<0.001). Daily activities, emotions, walking ability, work, social interaction, sleep and recreation were affected for 21 days after the rash in HZ patients, ranging from 60.79% to 83.83%, with sleep being the most affected (83.83%). The impact scores of pain and life dimensions in PHN patients ranged from 4.59 to 7.61 points on the ZBPI scale, which were higher than those in non-PHN patients (2.49-5.04) (t values ranged from 8.86 to 11.67, all P values <0.001). Conclusion: The proportion of pain in HZ patients after the diagnosis is high, and the pain is more obvious in patients with PHN and HZ patients aged 50 and older, which has a greater impact on their daily lives.
Male ; Humans ; Middle Aged ; Aged ; Adult ; Female ; Beijing ; Follow-Up Studies ; Herpes Zoster/epidemiology* ; Pain/epidemiology* ; Exanthema

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.
Humans ; Mesothelioma, Malignant ; Prognosis ; Nomograms ; Retrospective Studies ; Proportional Hazards Models