Objective To explore the molecular mechanism of Guben Zhike Pingchuan Granules in treating cough variant asthma(CVA)through network pharmacology and molecular docking technology;To use CVA model rats for validation;To provide a basis for the basic research and clinical application of Guben Zhike Pingchuan Granules.Methods TCMSP and BATMAN-TCM databases were used to retrieve the active components and corresponding targets of Guben Zhike Pingchuan Granules,and CVA disease targets were screened using OMIM,GeneCards,DrugBank,PharmGKB databases to obtain drug disease intersection targets.Cytoscape 3.10.1 software was used to construct the drug-component-target network and screen the key components;STRING database was used to construct protein-protein interaction(PPI)network and screen core targets;GO and KEGG enrichment analysis was conducted using DAVID platform;AutoDock Vina software was used to conduct molecular docking on the core targets and key components with high degree value respectively.CVA rat model was established by smoking combined with intraperitoneal and subcutaneous multi-point injection of ovalbumin.The rats were randomly divided into blank group,model group,montelukast sodium tablets group,Guben Zhike Pingchuan Granules low-and high-dosage groups.The groups received corresponding medicine for 15 d.HE staining was used to observe the morphology of lung tissue;ELISA was used to detect the contents of serum interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α);immunohistochemistry was used to detect the positive expressions of AKT,EGFR and NFKB1 in lung tissue.Results A total of 9 996 active components and 1 119 potential targets of Guben Zhike Pingchuan Granules,2 740 CVA targets,467 drug and disease intersection targets were screened out;PPI network topology analysis showed that AKT1,STAT3,EGFR,NFKB1 and MTOR were the core targets;the results of enrichment analysis showed that Guben Zhike Pingchuan Granules played an anti-inflammatory role in the treatment of CVA mainly through the interaction of EGFR/PI3K-Akt/NF-κB signaling pathway;molecular docking showed good binding ability between the core targets and key components,with a binding energy of<-7.0 kcal/mol for EGFR and Quercetin.Animal experiment results showed that after intervention with Guben Zhike Pingchuan Granules,the alveolar walls of the lung tissue in the model rats narrowed,the size of the alveoli became uniform,lymphocyte infiltration improved significantly,bronchioles contracted,and mucus in the lumen decreased;compared with the model group,the serum contents of IL-1β and TNF-α decreased in Guben Zhike Pingchuan Granules low-and high-dosage groups and montelukast sodium tablets group,and the positive expressions of AKT,EGFR and NFKB1 in lung tissue decreased(P<0.05,P<0.01).Conclusion Guben Zhike Pingchuan Granules may mediate the inflammatory response through the EGFR/PI3K-Akt/NF-κB signaling pathway,significantly improve the structural damage of CVA lung tissue,inhibit inflammatory cell infiltration,down-regulate the expressions of inflammatory factors,and thus exert therapeutic effects on CVA.

Schizophrenia is a prevalent mental-behavioral disorder characterized by perceptual disturbances,affective dysregulation,and behavioral abnormalities.In traditional Chinese medicine,it is classified under"manic depressive psychosis"according to its symptomatology.The concepts of"spirit,soul,and inferior spirit"originate from Lingshu·Benshen.Drawing on the concept of"spirit governs the soul and inferior spirit"from Lei Jing,this study explored schizophrenia pathogenesis and treatment from the perspective of the three-level regulation of spirit,soul,and inferior spirit.The core pathogenesis involves failure of spirit to govern as the root cause,disruption of soul homing as the pathodynamic process,and the loss of inferior spirit's somatic functional expression as the manifestation.The pathological locations are the heart,liver,and lungs.Therapeutic strategies are developed according to the pathological transmission pattern"spirit derangement,soul floating,inferior spirit dissipation,"forming a treatment system that emphasizes"calming the heart and tranquillization,restoring its control to solidify the root;suppressing the liver soul and regulating the central mechanism to pacify excess to stop mania;purifying the lungs and calming the inferior spirit to restore its clarity and regulate sensory perception and restore cognition."The treatment emphasizes the synergistic use of"calming the spirit,stabilizing the soul,and soothing the inferior spirit,"and combines acupuncture and repetitive transcranial magnetic stimulation and other treatments to treat both the manifestation and root cause of schizophrenia.Exploring the syndrome differentiation and treatment of schizophrenia from the perspective of spirit,soul,and inferior spirit,aiming to provide a theoretical basis for the treatment of schizophrenia with traditional Chinese medicine.

Schizophrenia is a prevalent mental-behavioral disorder characterized by perceptual disturbances,affective dysregulation,and behavioral abnormalities.In traditional Chinese medicine,it is classified under"manic depressive psychosis"according to its symptomatology.The concepts of"spirit,soul,and inferior spirit"originate from Lingshu·Benshen.Drawing on the concept of"spirit governs the soul and inferior spirit"from Lei Jing,this study explored schizophrenia pathogenesis and treatment from the perspective of the three-level regulation of spirit,soul,and inferior spirit.The core pathogenesis involves failure of spirit to govern as the root cause,disruption of soul homing as the pathodynamic process,and the loss of inferior spirit's somatic functional expression as the manifestation.The pathological locations are the heart,liver,and lungs.Therapeutic strategies are developed according to the pathological transmission pattern"spirit derangement,soul floating,inferior spirit dissipation,"forming a treatment system that emphasizes"calming the heart and tranquillization,restoring its control to solidify the root;suppressing the liver soul and regulating the central mechanism to pacify excess to stop mania;purifying the lungs and calming the inferior spirit to restore its clarity and regulate sensory perception and restore cognition."The treatment emphasizes the synergistic use of"calming the spirit,stabilizing the soul,and soothing the inferior spirit,"and combines acupuncture and repetitive transcranial magnetic stimulation and other treatments to treat both the manifestation and root cause of schizophrenia.Exploring the syndrome differentiation and treatment of schizophrenia from the perspective of spirit,soul,and inferior spirit,aiming to provide a theoretical basis for the treatment of schizophrenia with traditional Chinese medicine.

Objective To explore the molecular mechanism of Guben Zhike Pingchuan Granules in treating cough variant asthma(CVA)through network pharmacology and molecular docking technology;To use CVA model rats for validation;To provide a basis for the basic research and clinical application of Guben Zhike Pingchuan Granules.Methods TCMSP and BATMAN-TCM databases were used to retrieve the active components and corresponding targets of Guben Zhike Pingchuan Granules,and CVA disease targets were screened using OMIM,GeneCards,DrugBank,PharmGKB databases to obtain drug disease intersection targets.Cytoscape 3.10.1 software was used to construct the drug-component-target network and screen the key components;STRING database was used to construct protein-protein interaction(PPI)network and screen core targets;GO and KEGG enrichment analysis was conducted using DAVID platform;AutoDock Vina software was used to conduct molecular docking on the core targets and key components with high degree value respectively.CVA rat model was established by smoking combined with intraperitoneal and subcutaneous multi-point injection of ovalbumin.The rats were randomly divided into blank group,model group,montelukast sodium tablets group,Guben Zhike Pingchuan Granules low-and high-dosage groups.The groups received corresponding medicine for 15 d.HE staining was used to observe the morphology of lung tissue;ELISA was used to detect the contents of serum interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α);immunohistochemistry was used to detect the positive expressions of AKT,EGFR and NFKB1 in lung tissue.Results A total of 9 996 active components and 1 119 potential targets of Guben Zhike Pingchuan Granules,2 740 CVA targets,467 drug and disease intersection targets were screened out;PPI network topology analysis showed that AKT1,STAT3,EGFR,NFKB1 and MTOR were the core targets;the results of enrichment analysis showed that Guben Zhike Pingchuan Granules played an anti-inflammatory role in the treatment of CVA mainly through the interaction of EGFR/PI3K-Akt/NF-κB signaling pathway;molecular docking showed good binding ability between the core targets and key components,with a binding energy of<-7.0 kcal/mol for EGFR and Quercetin.Animal experiment results showed that after intervention with Guben Zhike Pingchuan Granules,the alveolar walls of the lung tissue in the model rats narrowed,the size of the alveoli became uniform,lymphocyte infiltration improved significantly,bronchioles contracted,and mucus in the lumen decreased;compared with the model group,the serum contents of IL-1β and TNF-α decreased in Guben Zhike Pingchuan Granules low-and high-dosage groups and montelukast sodium tablets group,and the positive expressions of AKT,EGFR and NFKB1 in lung tissue decreased(P<0.05,P<0.01).Conclusion Guben Zhike Pingchuan Granules may mediate the inflammatory response through the EGFR/PI3K-Akt/NF-κB signaling pathway,significantly improve the structural damage of CVA lung tissue,inhibit inflammatory cell infiltration,down-regulate the expressions of inflammatory factors,and thus exert therapeutic effects on CVA.

Objective:To explore the trends and outcomes for heart transplantation (HT) in elderly recipients and further examine the related risk factors.Methods:Between June 2004 and December 2021, retrospective review was conducted for the relevant clinical data and age distribution of 1044 HT recipients aged ≥18 year at Fuwai Hospital. The study population was assigned into two groups of elder (≥60 year, n=877) and non-elder (<60 year, n=157). Subgroup analysis was made between recipients aged <65 year (n=107) and those aged ≥ 65 year (n=50) in elder group. Baseline demographic profiles, clinical data, in-hospital and one-year post-transplant mortality and long-term survival were compared between two groups. Then a further comparison of long-term survival was conducted among the groups of non-elder, elder aged <65 year and elder aged ≥65 year. Cox proportional risk regression and multivariate Logistic regression models were utilized for examining the relevant risk factors for cumulative survival rate and short-term mortality. Kaplan-Meier analysis was employed for plotting survival curves and Log-rank test for comparison. Multivariate Cox proportional risk regression model was utilized for examining the relevant risk factors for cumulative survival rate and multivariate Logistic regression model for analyzing the relevant risk factors for short-term mortality. After adjusting for other confounding factors, the impact of recipient age on survival post-HT was determined.Results:The number of elderly HT recipients spiked annually at our center while average age of adult recipients and average age of elderly recipients have remained relatively constant. The median follow-up period was 6.5 years. Regarding baseline data, statistically significant differences existed in ratio of males [84.7%(113/157) vs 77.5%(687/877)], hypertension history [20.4%(32/157) vs 8.9%(79/877)], smoking history [47.1%(74/157) vs 36.1%(320/877)], diabetic history [33.8%(53/157) vs 14.7%(130/877)], preoperative ICD/CRT/CRT-D implantation [28.0%(44/157) vs 18.0%(160/877)], value of creatinine [(105.3±25.3) vs (96.8±35.0) μmol/L], IMPACT score [(6.9±2.4) vs (4.2±2.9) point], serum total bilirubin [19.7(13.6, 30.3) vs 23.7(15.8, 36.8) μmol/L], mean pulmonary arterial pressure [(26.0±10.3) vs (29.7±11.0) mmHg (1 mmHg=0.133 kPa)] and ischemic duration [(274.7±105.6) vs (296.0±120.4) min] (all P<0.05). No significant inter-group difference existed in in-hospital mortality [4.5%(7/157) vs 4.7%(42/887)] or 1-year mortality [5.7%(9/157) vs 6.5%(58/887)] ( P=0.88, P=0.70); in-hospital mortality and 1-year postoperative mortality of recipients aged ≥65 years 10.0%(5/50) and 14.0%(7/50) were both higher than those aged <65 year [1.9%(2/107), 1.9%(2/107)]. The differences were both statistically significant ( P=0.02, P<0.01). Kaplan-Meier survival analysis indicated that long-term survival rate was lower in elder group than that in non-elder group and the difference was statistically significant ( P=0.046). Long-term survival rate of elders aged ≥65 year was lower than that of non-elders aged <65 year and the difference was statistically significant ( P<0.01). Regression analysis indicated that age of recipient ≥65 year, preoperative creatinine ≥133 μmol/L, preoperative total bilirubin ≥25.65 μmol/L and preoperative support of extracorporeal membrane oxygenation (ECMO) were independent risk factors for short/long-term mortality post-HT. Conclusion:Although long-term prognosis of elderly recipients is slightly worse than that of non-elderly ones, in-hospital mortality and one-year postoperative mortality are similar between two groups. For elderly recipients with fewer comorbidities and better preoperative status, they should not be excluded from HT based solely upon age. The long-term prognosis of recipients aged ≥65 year remains poor and HT decisions should be made carefully.

Objective To investigate the improvement of oxygenation after the treatment of prone position in patients with severe acute respiratory distress syndrome (ARDS) caused by pneumocystis jirovecii pneumonia (PJP) after kidney transplantation. Methods Clinical data of 5 cases of moderate and severe ARDS caused by PJP after kidney transplantation were analyzed retrospectively, and clinical characteristics, treatment regimen and prognosis were summarized. Results Clinical manifestations of 5 patients were fever, dry cough, chest tightness, shortness ofbreath,sweating and fatigue, and body temperature fluctuated between 38 ℃ and 39 ℃, percutaneous arterial oxygen saturation(SpO₂) was gradually decreased, and respiratory distress symptoms were worsened. Pulmonary CT scan showed diffuse ground-glass shadow. After transfer to intensive care unit (ICU), immunosuppressive drugs were terminated, and all patients were given with compound sulfamethoxazole, caspofungin, low-dose glucocorticoids against pneumocystis jirovecii (PJ), oxygen therapy and other symptomatic supportive treatments. Four patients diagnosed with severe ARDS upon admission to ICU were treated in a prone position. One patient with moderate ARDS was not kept in a prone position. At 1 d after treatment in a prone position, partial pressure of arterial oxygen (PaO₂) and oxygenation index were increased, whereas alveolar-arterial oxygen difference (A-aDO₂) was decreased compared with before treatment (allP<0.05). Compared with 1 d after treatment, SpO₂, PaO₂ and oxygenation index were all increased, while A-aDO₂ was decreased at 4 d after treatment (all P<0.05). Box diagram showed that oxygenation index showed an overall upward trend after prone-position treatment, whereas A-aDO₂ showed an overall downward trend. The length of ICU stay of 5 patients was 14 (8, 29) d. All patients in a prone position did not develop complications, such as skin pressure sore, tube detachment and tube displacement, etc. Among 5 patients, 4 patients were mitigated, and 1 patient died of septic shock and multiple organ failure. Conclusions For both conscious and intubated patients, a prone position may significantly improve oxygenation and prognosis of patients with severe ARDS caused by PJP after kidney transplantation. Early diagnosis and accurate and standardized treatment play a pivotal role in enhancing cure rate.

Objective:To evaluate the mechanism of pancreatic interleukin-22 (IL-22) signaling pathway regulating insulin resistance (IR) in polycystic ovary syndrome (PCOS) rats.Methods:Postnatal 21 d SD rats were divided into control group and PCOS group with 10 rats in each group based on numbers randomly generated by computer. PCOS rats implanted with a silastic tube filled with dihydrotestosterone (DHT) at dosage of 7.5 mg. Their body weight was monitored weekly. At the end of the experiment, the intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin test (IPITT) were conducted, the serum IL-22 and fasting insulin (FINS) were monitored through the enzyme-linked immunosorbent assay (ELISA), and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The location and differential expression of the interleukin-22 receptor 1 (IL-22R1) in pancreatic β cells were observed by immunofluorescence staining, and the expressions of the IL-22, Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3) proteins were detected by Western blotting.Results:Compared with control group, the body weight was increased [(420.50±10.26) g vs. (314.40±6.54) g, P=0.003] and the serum level of IL-22 in PCOS group was decreased [(9.86±1.41) ng/L vs. (16.07±4.68) ng/L, P=0.038]. The levels of FINS and HOMA-IR were higher in PCOS group than in control group [(17.97±2.86) mU/L vs. (13.05±2.12) mU/L, P=0.001; 4.46±0.80 vs. 2.99±0.61, P=0.001]. The glucose levels in IPGTT test were significantly elevated in PCOS group in 30 min, 60 min and 90 min compared with control group [(15.58±1.86) mmol/L vs. (12.54±1.60) mmol/L, P=0.010;(10.71±2.07) mmol/L vs. (8.33±1.02) mmol/L, P=0.026; (7.47±1.36) mmol/L vs. (6.28±0.72) mmol/L, P=0.013], as well as the area under curve (AUC) [(1 248.71±164.23) mmol/(L·min) vs. (1 007.29±102.29) mmol/(L·min), P=0.010]. Following IPITT, compared with control group, PCOS group showed significantly higher 60 min [(3.12±0.28) mmol/L vs. (2.60±0.28) mmol/L, P=0.031], 90 min [(2.62±0.17) mmol/L vs. (2.10±0.33) mmol/L, P=0.026] and 120 min glucose level [(2.28±0.25) mmol/L vs. (1.90±0.24) mmol/L, P=0.033], as well as the AUC [(414.60±23.06) mmol/(L·min) vs. (359.40±39.95) mmol/(L·min), P=0.044]. The immunofluorescence results suggested that IL-22R1 and INS were colocalized in pancreatic β cells and the expression of IL-22R1 was lower in PCOS group than in control group (48.26±3.83 vs. 63.44±2.66, P=0.031). Further, the levels of pancreatic IL-22 and p-STAT3 protein were significantly lower in PCOS group than in control group (0.82±0.09 vs. 1.01±0.06, P=0.025; 0.77±0.09 vs. 1.01±0.07, P=0.015). Conclusion:Our results demonstrated that the abnormality of IL-22 may result in IR through attenuating the activation of STAT3 signaling pathway and decreasing the level of p-STAT3 in the pancreatic tissue of PCOS rats.

Objective:To evaluate the mechanism of pancreatic interleukin-22 (IL-22) signaling pathway regulating insulin resistance (IR) in polycystic ovary syndrome (PCOS) rats.Methods:Postnatal 21 d SD rats were divided into control group and PCOS group with 10 rats in each group based on numbers randomly generated by computer. PCOS rats implanted with a silastic tube filled with dihydrotestosterone (DHT) at dosage of 7.5 mg. Their body weight was monitored weekly. At the end of the experiment, the intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin test (IPITT) were conducted, the serum IL-22 and fasting insulin (FINS) were monitored through the enzyme-linked immunosorbent assay (ELISA), and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The location and differential expression of the interleukin-22 receptor 1 (IL-22R1) in pancreatic β cells were observed by immunofluorescence staining, and the expressions of the IL-22, Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3) proteins were detected by Western blotting.Results:Compared with control group, the body weight was increased [(420.50±10.26) g vs. (314.40±6.54) g, P=0.003] and the serum level of IL-22 in PCOS group was decreased [(9.86±1.41) ng/L vs. (16.07±4.68) ng/L, P=0.038]. The levels of FINS and HOMA-IR were higher in PCOS group than in control group [(17.97±2.86) mU/L vs. (13.05±2.12) mU/L, P=0.001; 4.46±0.80 vs. 2.99±0.61, P=0.001]. The glucose levels in IPGTT test were significantly elevated in PCOS group in 30 min, 60 min and 90 min compared with control group [(15.58±1.86) mmol/L vs. (12.54±1.60) mmol/L, P=0.010;(10.71±2.07) mmol/L vs. (8.33±1.02) mmol/L, P=0.026; (7.47±1.36) mmol/L vs. (6.28±0.72) mmol/L, P=0.013], as well as the area under curve (AUC) [(1 248.71±164.23) mmol/(L·min) vs. (1 007.29±102.29) mmol/(L·min), P=0.010]. Following IPITT, compared with control group, PCOS group showed significantly higher 60 min [(3.12±0.28) mmol/L vs. (2.60±0.28) mmol/L, P=0.031], 90 min [(2.62±0.17) mmol/L vs. (2.10±0.33) mmol/L, P=0.026] and 120 min glucose level [(2.28±0.25) mmol/L vs. (1.90±0.24) mmol/L, P=0.033], as well as the AUC [(414.60±23.06) mmol/(L·min) vs. (359.40±39.95) mmol/(L·min), P=0.044]. The immunofluorescence results suggested that IL-22R1 and INS were colocalized in pancreatic β cells and the expression of IL-22R1 was lower in PCOS group than in control group (48.26±3.83 vs. 63.44±2.66, P=0.031). Further, the levels of pancreatic IL-22 and p-STAT3 protein were significantly lower in PCOS group than in control group (0.82±0.09 vs. 1.01±0.06, P=0.025; 0.77±0.09 vs. 1.01±0.07, P=0.015). Conclusion:Our results demonstrated that the abnormality of IL-22 may result in IR through attenuating the activation of STAT3 signaling pathway and decreasing the level of p-STAT3 in the pancreatic tissue of PCOS rats.

OBJECTIVE To study the improvement effects of Huorongcaohuangqi （HRCHQ） admixture decoction on mesangial proliferative glomerulonephritis （MsPGN）model rats and its mechanism . METHODS Totally 70 rats were divided into sham operation group （n＝10）and modeling group （n＝60）according to body weight . Sham operation group underwent sham operation，and MsPGN model was induced by immunological method （Freund’s adjuvant+BSA+lipopolysaccharide ）in modeling group. After successfully modeling ，50 rats were randomly divided into model group ，HRCHQ high -dose，medium-dose and low - dose groups （4.05，2.03，1.02 g/kg），Benazepril hydrochloride tablet group （20 mg/kg），with 10 rats in each group . Sham operation group and model group were given distilled water intragastrically ；other groups were given relevant medicine intragastrically 15 mL/kg，once a day ，for consecutive 5 weeks. After last administration ，the contents of total protein ，albumin and urea nitrogen were determined in the serum of rats . The expressions of transforming growth factor β1（TGF-β1）and tumor necrosis factor α（TNF-α）in renal tissue were detected by immunohistochemistry ；the expression of complement C 3 in renal tissue was detected by immunofluorescence . The phosphorylation level of phosphatidylinositol 3 kinase/protein kinase B/glycogen synthase kinase 3β（PI3K/Akt/GSK-3β） signal pathway related proteins and expression level of fibronectin （FN） in renal tissue were detected by Western blot . RESULTS Compared with model group，the serum contents of total protein and albumin were increased significantly in HRCHQ high -dose group （P＜0.05 or P＜0.01）. The serum content of urea nitrogen ， the E-mail：Houxia_75@163.com expressions of TGF -β1，TNF-α，FN and complement C 3，and the phosphorylation levels of PI 3K，Akt and GSK 3β protein were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS HRCHQ can improve MsPGN by reducing the proliferation of mesangial cells and inhibiting the activity of PI 3K/ Akt/GSK3β signaling pathway .

Purpose: Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer. Materials and Methods: A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits. Results: Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse. Conclusion We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.