The plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) are native species unique to the Qinghai-Tibetan Plateau with successful adaptation to the hypoxic environment. In this study, the number of red blood cells, hemoglobin concentration, mean hematocrit and mean volume of red blood cells were measured in plateau zokors and plateau pikas at different altitudes. Hemoglobin subtypes of two plateau animals were identified by mass spectrometry sequencing. The forward selection sites in two animals' hemoglobin subunits were analyzed by PAML4.8 program. Homologous modeling was used to analyze the effect of forward selection sites on the affinity of hemoglobin to oxygen. The adapting strategies of plateau zokors and plateau pikas to hypoxia at different altitudes were analyzed through comparing blood parameters between the two species. The results indicated that, with increasing altitudes, plateau zokors responded to hypoxia by increasing red blood cell count and decreasing red blood cell volume, while plateau pikas took the opposite strategies to plateau zokors. In erythrocytes of plateau pikas, both adult α₂β₂ and fetal α₂ε₂ hemoglobins were identified, while erythrocytes of plateau zokors only had adult α₂β₂ hemoglobin, however the affinities and the allosteric effects of the hemoglobin of plateau zokors were significantly higher than those of plateau pikas. Mechanistically, in the α and β subunits of hemoglobin of plateau zokors and pikas, the numbers and the sites of the positively selected amino acids as well as the side chain groups polarities and orientations of the amino acids differed significantly, which may result in the difference of the affinities to oxygen of hemoglobin between plateau zokors and pikas. In conclusion, the adaptive mechanisms to respond to hypoxia in blood properties of plateau zokors and plateau pikas are species-specific.
Animals ; Altitude ; Amino Acids ; Hemoglobins ; Hypoxia ; Lagomorpha

Terpenoids are important secondary metabolites of plants that possess both pharmacological activity and economic value. Terpene synthases(TPSs) are key enzymes in the synthesis process of terpenoids. In order to investigate the TPS gene family members and their potential functions in Schizonepeta tenuifolia, this study conducted a systematic analysis of the TPS gene family of S. tenuifolia based on the whole genome data of S. tenuifolia using bioinformatics methods. The results revealed 57 StTPS members identified from the genome database of S. tenuifolia. The StTPS family members encoded 285-819 amino acids, with protein molecular weights ranging from 32.75 to 94.11 kDa, all of which were hydrophilic proteins. The StTPS family members were mainly distributed in the cytoplasm and chloroplasts, exhibiting a random and uneven physical localization pattern. Phylogenetic analysis showed that the StTPS genes family were divided into six subgroups, mainly belonging to the TPS-a and TPS-b subfamilies. Promoter analysis predicted that the TPS gene family members could respond to various stressors such as light, abscisic acid, and methyl jasmonate(MeJA). Transcriptome data analysis revealed that most of the TPS genes were expressed in the roots of S. tenuifolia, and qRT-PCR analysis was conducted on genes with high expression in leaves and low expression in roots. Through the analysis of the TPS gene family of S. tenuifolia, this study identified StTPS5, StTPS18, StTPS32, and StTPS45 as potential genes involved in sesquiterpene synthesis of S. tenuifolia. StTPS45 was cloned for the construction of an prokaryotic expression vector, providing a reference for further investigation of the function and role of the TPS gene family in sesquiterpene synthesis.
Phylogeny ; Terpenes/metabolism* ; Plant Proteins/metabolism* ; Lamiaceae/genetics* ; Sesquiterpenes

Objective:To study the main active components and potential mechanism of the treatment of ovarian cancer by Scutellariae Barbatae Herba - Cremastrae Pseudobulbus Pleiones Pseudobulbus based on network pharmacology and in vitro cell experiments.Methods:TCMSP and SwissTargetPrediction databases were used to retrieve and collect the active components and targets of Scutellariae Barbatae Herba - Cremastrae Pseudobulbus Pleiones Pseudobulbus, and four databases including GeneCards, OMIM, DrugBank and DisGeNET were used to search the targets related to ovarian cancer. After screening the common potential targets of Scutellariae Barbatae Herba - Cremastrae Pseudobulbus Pleiones Pseudobulbus and ovarian cancer, the STRING database was used to realize the construction of PPI network interacting with the proteins of the two common targets. DAVID database was used for GO and KEGG enrichment analysis. Cytoscape 3.9.0 software was used to construct the "active component-target-pathway" network. Finally, the key targets and pathways were validated in vitro. MTT method was used to detect the proliferation inhibition rate of human ovarian cancer SKOV3 cells with different concentrations of Quercetin and sitosterol. Human ovarian cancer SKOV3 cells were divided into control group, Quercetin group and sitosterol group according to the random number table method. After corresponding drug intervention for 48 hours, the effects of Quercetin and sitosterol on SKOV3 cell cloning ability were detected by clone formation experiment, the levels of Akt1, VEGFA, Caspase-3 mRNA in each group were detected by PCR, and the protein expressions of PI3K, Akt, p-Akt, Caspase-3, and VEGFA in cells were detected by Western blot.Results:Through screening, 29 effective chemical components in Scutellariae Barbatae Herba and 3 effective chemical components in Cremastrae Pseudobulbus Pleiones Pseudobulbus were obtained, including 2 components in total. 291 drug-related targets, 1969 potential targets of ovarian cancer were acquired. There were 137 common targets of "Scutellariae Barbatae Herba - Cremastrae Pseudobulbus Pleiones Pseudobulbus" and the drug-disease intersection of ovarian cancer. Through GO functional analysis, 930 items were obtained, involving 722 biological processes, 76 cellular components and 132 molecular functions. KEGG enrichment analysis involved 169 signaling pathways, including tumor pathway, PI3K-Akt signaling pathway, P-53 signaling pathway, IL-17 signaling pathway, etc. In vitro experiment results showed that cell proliferation inhibition rate increased and cell cloning ability decreased in Quercetin and sitosterol groups; The levels of Akt1 and VEGFA mRNA in Quercetin group and sitosterol group decreased ( P<0.01 or P<0.05), the expression of Caspase-3 mRNA and protein increased ( P<0.01), and the expressions of PI3K, p-Akt and VEGFA protein decreased ( P<0.01). Conclusion:Scutellariae Barbatae Herba - Cremastrae Pseudobulbus Pleiones Pseudobulbus inhibits the occurrence and development of ovarian cancer through multi target and multi pathway synergistic effects, and can induce SKOV3 cell apoptosis by regulating the expressions of key genes such as AKT1, VEGFA, Caspase-3, and PI3K/Akt pathway.

OBJECTIVE: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival (PFS) and overall survival (OS) of limited-stage small cell lung cancer (LS-SCLC) patients after the first-line chemoradiotherapy. METHODS: The data of 67 LS-SCLC patients who received combined treatment of CM and Western medicine (WM) between January 2013 and May 2020 at the outpatient clinic of Guang'anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method (Kaplan-Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. RESULTS: The median PFS in the CM and WM combination treatment group and the WM group were 19 months (95% CI: 12.357-25.643) vs. 9 months (95% CI: 5.957-12.043), HR=0.43 (95% CI: 0.27-0.69, P<0.001), respectively. The median OS in the CM and WM combination group and the WM group were 34 months (95% CI could not be calculated) vs. 18.63 months (95% CI: 16.425-20.835), HR=0.40 (95% CI: 0.24-0.66, P<0.001), respectively. Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months (P<0.001). CONCLUSION The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone. (Registration No. ChiCTR2200056616).
Humans ; Small Cell Lung Carcinoma/drug therapy* ; Lung Neoplasms/drug therapy* ; Retrospective Studies ; Prognosis ; Combined Modality Therapy

To explore the predictive value of preoperative serum CYFRA 21-1 in colorectal cancer (CRC) resection patients. In this retrospective study, 456 patients with CRC who received surgical treatment in the Department of General Surgery, Affiliated Hospital of Nantong University from January 2016 to February 2018 were analyzed. Preoperative CYFRA 21-1, CEA, CA19-9 and pathological data of the study subjects were collected. Determine the cut-off value of CYFRA 21-1 based on the X-tile. Chi-square test or Fisher exact probability test were used to compare clinicopathological features in different CYFRA 21-1 level groups. Univariate and multivariate regression analysis of factors affecting 5-year overall survival (OS) and disease-free survival (DFS). Kaplan-Meier survival curves were used to analyze 5-year differences in OS and DFS in CRC patients with different levels of CYFRA 21-1, CEA and CA19-9. Receiver operating characteristic(ROC) was adopted. ROC curves were used to analyze the prognostic efficacy of CYFRA21-1 for CRC, and nomogram maps were used to predict 1, 3, and 5-year survival rates. The results showed that the optimal cut-off values of serum CYFRA 21-1, CEA and CA19-9 were 4.9 ng/ml, 29.2 ng/ml and 72.8 U/ml, respectively. Different gender, tumor size, location, degree of differentiation, depth of invasion, lymph node metastasis and tumor node metastasis (TNM) classification stage were significantly different between the two groups with high and low CYFRA 21-1, the P-values were 0.018,<0.001,<0.001,<0.001, 0.002, 0.001, 0.003, respectively. CYFRA 21-1 (≥4.9 ng/ml) was an independent risk factor for 5-year OS (HR: 4.008, 95%CI: 2.309-6.958, P<0.001) and DFS (HR: 3.75, 95%CI: 2.227-6.314, P<0.001) in CRC patients. CYFRA 21-1 predicts a 5-year AUC of 0.725 and 0.720 for OS and DFS, respectively, and 0.804 and 0.827 for the combination of CEA and CA19-9. Based on the results of multivariate Cox regression analysis, nomogram graphs of OS and DFS were established, the C-indexes were 0.799 and 0.803, respectively. In conclusion, preoperative serum CYFRA 21-1 level may be an independent risk factor affecting the prognosis of patients with colorectal cancer. The prognostic model established by CYFRA 21-1 combined with CEA, CA19-9 and TNM stages may provide references for the prevention of CRC recurrence and clinical decision-making.
Humans ; Colorectal Neoplasms/pathology* ; CA-19-9 Antigen ; Retrospective Studies ; Neoplasm Staging ; Neoplasm Recurrence, Local/pathology* ; Biomarkers, Tumor

To explore the predictive value of preoperative serum CYFRA 21-1 in colorectal cancer (CRC) resection patients. In this retrospective study, 456 patients with CRC who received surgical treatment in the Department of General Surgery, Affiliated Hospital of Nantong University from January 2016 to February 2018 were analyzed. Preoperative CYFRA 21-1, CEA, CA19-9 and pathological data of the study subjects were collected. Determine the cut-off value of CYFRA 21-1 based on the X-tile. Chi-square test or Fisher exact probability test were used to compare clinicopathological features in different CYFRA 21-1 level groups. Univariate and multivariate regression analysis of factors affecting 5-year overall survival (OS) and disease-free survival (DFS). Kaplan-Meier survival curves were used to analyze 5-year differences in OS and DFS in CRC patients with different levels of CYFRA 21-1, CEA and CA19-9. Receiver operating characteristic(ROC) was adopted. ROC curves were used to analyze the prognostic efficacy of CYFRA21-1 for CRC, and nomogram maps were used to predict 1, 3, and 5-year survival rates. The results showed that the optimal cut-off values of serum CYFRA 21-1, CEA and CA19-9 were 4.9 ng/ml, 29.2 ng/ml and 72.8 U/ml, respectively. Different gender, tumor size, location, degree of differentiation, depth of invasion, lymph node metastasis and tumor node metastasis (TNM) classification stage were significantly different between the two groups with high and low CYFRA 21-1, the P-values were 0.018,<0.001,<0.001,<0.001, 0.002, 0.001, 0.003, respectively. CYFRA 21-1 (≥4.9 ng/ml) was an independent risk factor for 5-year OS (HR: 4.008, 95%CI: 2.309-6.958, P<0.001) and DFS (HR: 3.75, 95%CI: 2.227-6.314, P<0.001) in CRC patients. CYFRA 21-1 predicts a 5-year AUC of 0.725 and 0.720 for OS and DFS, respectively, and 0.804 and 0.827 for the combination of CEA and CA19-9. Based on the results of multivariate Cox regression analysis, nomogram graphs of OS and DFS were established, the C-indexes were 0.799 and 0.803, respectively. In conclusion, preoperative serum CYFRA 21-1 level may be an independent risk factor affecting the prognosis of patients with colorectal cancer. The prognostic model established by CYFRA 21-1 combined with CEA, CA19-9 and TNM stages may provide references for the prevention of CRC recurrence and clinical decision-making.
Humans ; Colorectal Neoplasms/pathology* ; CA-19-9 Antigen ; Retrospective Studies ; Neoplasm Staging ; Neoplasm Recurrence, Local/pathology* ; Biomarkers, Tumor

Objective To analyze the relationship between follow-up service, personal characteristics, lifestyle and blood sugar management of diabetic patients in Gansu Province, and put forward scientific suggestions on influencing blood sugar management of diabetic patients. Methods Based on the data of the 6th National Health Service Questionnaire, 273 subjects were included. Chi-square test and unconditional logistic regression were used to analyze the blood glucose control and its influencing factors of diabetic patients. Results A total of 39.56% patients' blood sugar status was well controlled. 76.92% patients signed up for family doctor service, and 77.66% patients took hypoglycemic drugs according to the law of doctor's advice. There were significant differences in blood sugar control among patients in different regions, educational levels and occupational types (P <0.05) , logistic regression analysis showed that Hui patients (OR=0.21), doctors without family contract (OR=2.86) and patients taking hypoglycemic drugs intermittently (OR = 6.58). Conclusion The blood sugar control rate of diabetic patients in Gansu is low, and the nationality, contracted family doctors and medication plan affect the blood sugar control level of patients. In order to ensure the high efficiency of follow-up treatment, the related follow-up services provided by primary medical institutions, it is necessary to provide self-management programs that meet the individual characteristics and meet the needs of the disease.

Objective: To observe the efficacy of long-retaining scalp acupuncture plus interactive training in improving upper- extremity dysfunction in cerebral stroke patients. Methods: Ninety-five patients with upper-extremity dysfunction after cerebral stroke were randomized into two groups, with 48 cases in the treatment group and 47 cases in the control group. Conventional internal medicine treatment was offered to both groups. In both groups, Anterior Oblique Line of Vertex-temporal (MS 6, the middle 2/5) and Posterior Oblique Line of Vertex-temporal (MS 7, the middle 2/5) were selected from the same side of the brain lesion (the side apposing to the hemiplegic limb) for scalp acupuncture treatment. In the treatment group, the scalp acupuncture needles were retained for 7 h, in combination with interactive training, while the needles were also retained for 7 h in the control group but without interactive training. Prior to treatment and at 2-week and 4-week treatment, the two groups were scored using the functional test for the hemiplegic upper extremity-Hong Kong (FTHUE-HK) and simplified Fugl-Meyer assessment-upper extremity (FMA-UE). Results: The total effective rate was 97.9％ in the treatment group, higher than 74.5％ in the control group (P<0.01). The FTHUE-HK score was higher at 2-week and 4-week treatment than before treatment in both groups, presenting statistically significant intra-group differences (all P<0.001); the FTHUE-HK score was higher at 4-week treatment than at 2-week treatment in both groups, presenting statistically significant intra-group differences (both P<0.001). At 2-week and 4-week treatment, the FTHUE-HK score was higher in the treatment group than in the control group, showing significant between-group differences (both P<0.05). During the whole treatment process, the treatment group had higher FTHUE-HK scores compared with the control group, but there was no statistical significance comparing the change of the score between the two groups at 2-week treatment (P>0.05), while the between-group difference in the change of the score was statistically significant at 4-week treatment (P<0.05). The FMA-UE score was higher at 2-week and 4-weeks treatment than before treatment in both groups, presenting statistically significant intra-group differences (all P<0.001); the FMA-UE score was higher at 4-week treatment than at 2-week treatment in both groups, presenting statistically significant intra-group differences (both P<0.001). At 2-week and 4-week treatment, the FMA-UE was higher in the treatment group than in the control group, and the between-group differences were statistically significant (both P<0.01). The FMA-UE score rose gradually with the increase of treatment session, and there was statistical significance comparing the change of the score between the two groups at 2-week and 4-week treatment, respectively (both P<0.05). Conclusion: Long-retaining scalp acupuncture plus interactive training results in more significant efficacy than long-retaining scalp acupuncture alone in improving the upper-limb dysfunction after cerebral stroke and the advantage becomes more notable after 2-week consecutive treatment.

Objective:The study investigated and analyzed the health-related quality of life of diabetes patients in Gansu province before and after the healthcare reform and its influencing factors, so as to provide scientific evidence to improve the health-related quality of life of diabetes patients.Methods:The study used data of the fourth and sixth national health service household survey in Gansu province before (2008) and after (2018) medical reform separately, and EQ-5D health utility index was calculated on the basis of Chinese time frade-off values for EuroQol Five-Dimensions Questionnaire Utility Value scoring system.Results:Compared with the period before the healthcare reform, the five dimensions of EQ-5D for residents, aged 15 and above in Gansu, changed significantly after the healthcare reform: action capability improved by 8.08% (27.43% vs. 19.35%), self-care improved by 16.16% (26.55% vs. 10.39%), normal activity improved by 8.97% (28.32% vs. 19.35%), pain/discomfort worsened by 1.38% (38.05% vs. 39.43%), anxiety/depression worsened by 1.83% (16.81% vs. 18.64%), and the EQ-VAS score increased by 3.36 (60.53 vs. 63.89). The health utility index increased by 0.04 (0.83 vs. 0.87). Multivariate regression analysis results showed that the dimension influence factors were not completely consistent, on the whole, the health-related quality of life of diabetes patients with older age, lower education level, no physical exercise and multi chronic diseases was worse ( P<0.05), and multiple chronic disease had the most serious effect on the health of patients with diabetes. The health-related quality of life of diabetes patients with the medical insurance in urban area and after the new medical reform was higher ( P<0.05). Conclusion:The new healthcare reform has active influence on the health-related quality of life of diabetes patients in Gansu province, health care providers and policy makers should pay attention to the impacts of multi prechronic diseases on the health-related quality of life of diabetes patients and the mental health of patients with diabetes.

Objective:To observe the effect of Zengmian Yiliu （ZMYL） formula and its effective components （PAWU） on the growth inhibition of ovarian cancer stem cell transplanted tumor in nude mice and the Notch signal receptor （Notch） / Notch signal ligand 1 （Jagged1） signal pathway in tumor tissue. Method:Ovarian cancer stem cells were cultured in serum-free suspension to establish the transplanted tumor model of ovarian cancer stem cells in nude mice， and then divided into model group， ZMYL group （36 g·kg^-1）， PAWU group （5.8 g·kg^-1）， cisplatin （DDP） group （2.5 g·kg^-1）， and PAWU （5.8 g·kg^-1） + DDP group （2.5 mg·kg^-1）.After successful modeling， the drugs were given by gavage for 21 days.To observe the effect of Zengmian Yiliu decoction and its effective components on tumor weight in nude mice， the morphological changes of tumor cells were observed under light microscope， immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）were used to detect the expressions of Notch 1， Jagged1， Hairy and enhancer of split 1 （Hes1） protein and mRNA in tumor tissues. Result:The tumor inhibition rates of ZMYL， PAWU， DDP and combination groups were 35.91%， 32.94%， 57.65% and 69.05%， respectively.Compared with the model group， the tumor weight of ZMYL group， PAWU group， DDP group and combination groups decreased significantly （P<0.05）.Compared with PAWU group， the tumor weight of combination groups decreased significantly （P<0.05）.Immunohistochemistry showed that compared with the model group， the positive expressions of Notch1， Jagged1 in ZMYL group， PAWU group， DDP group and combination groups were down-regulated （P<0.05），and the positive expressions of Hes1 in ZMYL group， DDP group and combination groups were down-regulated （P<0.05）.Compared with combination groups， the positive expressions of Notch1， Jagged1 and Hes1 in ZMYL group， PAWU group， DDP group were up-regulated （P<0.05）. Real time PCR showed that compared with the model group， the expressions of Notch1 mRNA in ZMYL group， PAWU group， DDP group and combination groups decreased significantly （P<0.05）.Compared with model group， the expressions of Jagged1 and Hes1 mRNA in ZMYL group， PAWU group and combination groups decreased significantly （P<0.05）.Compared with DDP group， the expressions of Notch1， Jagged1 and Hes1 mRNA in combination groups decreased significantly （P<0.05）. Conclusion:The growth of ovarian cancer stem cells transplanted in nude mice can be inhibited by Zengmian Yiliu formula and its effective components.The effective components have a significant synergistic effect in the combination with cisplatin.Its mechanism is correlated to the inhibition of Notch/Jagged1 signaling pathway activation.