Objective To explore the impact of pH value of the reaction system on the properties of bovine hemoglobin modified with aldehydeated polyethylene glycol(PEG-bHb).Methods PEG-bHb conjugates were synthesized under varying pH conditions(6.0,6.5,7.4 and 8.0)of the reaction system while consistent molar ratios,temperature,and reaction time were maintained.The structural and functional attributes of PEG-bHb were characterized.Results The proportion of methemoglobin decreased with an increase in pH.In a weakly acidic reaction environment,the PEG-bHb was found to be relatively highly modified.At pH 6.5,the average number of PEG chains attached to the bHb surface was 6.86±0.38.Selective PEG modification of the N-terminal α-NH2 groups was more pronounced under weakly acidic conditions.Specifically,at pH 6.5,the modification efficiency of the N-terminal α-NH2 groups of bHb by aldehyde-activated PEG reached 95.4％for the α-chains and 99.3％for the β-chains.The PEG modification influenced the heme region microenvi-ronment of bHb,with minimal structural impact observed at pH 6.5.After modification,the oxygen affinity of PEG-bHb was enhanced,the Hill coefficient was reduced,and there were significant increases in colloid osmotic pressure,viscosity,and particle size,all of which differed markedly from the unmodified bHb group(P＜0.001).Conclusion The synthesis of PEG-bHb under weakly acidic conditions can result in a high degree of selective modification of the N-terminal α-NH2 groups and an overall high degree of modification.

Aim To explore the effects of ethanol extraction of Dysosma versipellis on the proliferation and apoptosis of renal clear cell carcinoma OS-RC-2 cells and the underlying mechanism. Methods After treated with Dysosma versipellis, the proliferation of OS-RC-2 cells was detected by the CCK-8 assay and clone formation assay. The migration rate of cells was detected by thewound healing assay and Transwell assay. The level of ROS was detected by the reactive oxygen detection kit. The common targets between Dysosma versipellis and ROS were obtained by the network pharmacology. The above common targets were analyzed by KEGG. The apoptosis rate and cell cycle were detected by the flow cytometry, and the key proteins of MAPK signaling pathway and the levels of apoptosis related proteins were measured by Western blot. Results The results showed that Dysosma versipellis significantly inhibited the cell viability and migration ability of 0S-RC-2 cells, and up-regulated the level of ROS. Network pharmacology analysis showed a total of 165 common targets between Dysosma versipellis and ROS. KEGG analysis of the common targets revealed that there were significant changes in the MAPK signaling pathway. The results of Western blot showed that after treated with Dysosma versipellis, the protein level of JNK and the ratio of p-ERK/ERK were down-regulated. Besides, the protein level of caspase-9 and Bcl-2 declined, while the levels of cleaved caspase-9 and Bax were promoted. The flow cytometry results showed that Dysosma versipellis could significantly promote the apoptosis rate,down-regulate the cells in Gl-phase,while up-regulate the cells in G2/M-phase. The results of the rescue experiment showed that co-administration of NAC and Dysosma versipellis could significantly reverse the cell viability and apoptosis rate, the level of apop-totic related proteins, as well as the protein levels of MAPK pathway,when compared to treated with Dysosma versipellis alone in OS-RC-2. Conclusion In summary, Dysosma versipellis may inhibit the MAPK signaling pathway via the changes in ROS,further promoting apoptosis rate and decline cell proliferation in OS-RC-2 cell line.

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.
Humans ; Male ; Adult ; Middle Aged ; Aged ; Female ; Stroke Volume ; Stellate Ganglion/surgery* ; Ventricular Function, Left ; Cardiomyopathies/complications* ; Tachycardia, Ventricular/therapy* ; Treatment Outcome ; Catheter Ablation

Humans ; Mutation ; Cholestasis, Intrahepatic

ObjectiveWhether blood urea nitrogen （BUN） can help increase risk stratification of simplified pulmonary embolism severity index （sPESI） in intensive care unit （ICU） still remains unknown. MethodsA total of 250 patients diagnosed as acute pulmonary embolism （APE） at ICU admission from medical information mart for intensive care Ⅲ database （MIMIC） were included in this retrospective study. The 30-day mortality was defined as the primary outcome. The optimal cut-off values of BUN and sPESI were calculated based on the maximum Youden index of receiver operating characteristic （ROC） curves. The Kaplan-Meier curves were used to evaluate the risk stratification ability of BUN， sPESI， and their combinations in the total cohort and subgroups. ResultsBUN and sPESI were both independent predictors for the 30-day mortality. The optimal cut-off value of BUN was 21.5 mg/dL and that of sPESI was 2.5. The 30-day mortality was 41.38% in high-risk group with BUN ≥21.5 mg/dL and sPESI ≥3， which was higher than that in group with sPESI ≥1 （14.28%）. And it was 4.07% in low-risk group with BUN ≤21.5 mg/dL and sPESI ≤2， which was near that of the group with sPESI =0 （3.85%）. ConclusionsBUN can help define a higher risk group with sPESI in APE admitted to ICU， which can contribute to the clinical management.

Gloeostereum incarnatum has edible and medicinal value and was first cultivated and domesticated in China. We sequenced the G. incarnatum monokaryotic strain GiC-126 on an Illumina HiSeq X Ten system and obtained a 34.52-Mb genome assembly sequence that encoded 16,895 predicted genes. We combined the GiC-126 genome with the published genome of G. incarnatum strain CCMJ2665 to construct a genetic linkage map (GiC-126 genome) that had 10 linkage groups (LGs), and the 15 assembly sequences of CCMJ2665 were integrated into 8 LGs. We identified 1912 simple sequence repeat (SSR) loci and detected 700 genes containing 768 SSRs in the genome; 65 and 100 of them were annotated with gene ontology (GO) terms and KEGG pathways, respectively. Carbohydrate-active enzymes (CAZymes) were identified in 20 fungal genomes and annotated; among them, 144 CAZymes were annotated in the GiC-126 genome. The A mating-type locus (MAT-A) of G. incarnatum was located on scaffold885 at 38.9 cM of LG1 and was flanked by two homeodomain (HD1) genes, mip and beta-fg. Fourteen segregation distortion markers were detected in the genetic linkage map, all of which were skewed toward the parent GiC-126. They formed three segregation distortion regions (SDR1–SDR3), and 22 predictive genes were found in scaffold1920 where three segregation distortion markers were located in SDR1. In this study, we corrected and updated the genomic information of G. incarnatum. Our results will provide a theoretical basis for fine gene mapping, functional gene cloning, and genetic breeding the follow-up of G. incarnatum.

OBJECTIVE: To observe the therapeutic effect between acupuncture combined with medication and simple medication on migraine and cerebral hemodynamics. METHODS: A total of 120 patients with migraine were randomized into an acupuncture plus medication group (60 cases, 3 cases dropped off) and a medication group (60 cases, 6 cases dropped off). In the medication group, flunarizine hydrochloride capsule was given orally before sleep, 10 mg a day. On the basis of the treatment in the medication group, acupuncture was applied at Sizhukong (TE 23), Shuaigu (GB 8), Taiyang (EX-HN 5), Fengchi (GB 20) and etc. in the acupuncture plus medication group, 30 min each time, once a day. Treatment for 4 weeks was required in both groups. Before and after treatment, the visual analogue scale (VAS) score, indexes of cerebral hemodynamic [blood flow velocity of anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA), vertebral artery (VA) and basilar artery (BA)] and total TCM syndrome score were observed, and the clinical therapeutic effect and the incidence of the adverse events were evaluated in both groups. RESULTS: Compared before treatment, the VAS scores, the blood flow velocity of ACA, MCA, PCA, VA, BA and the total TCM syndrome scores were decreased in both groups ( CONCLUSION Acupuncture combined with flunarizine hydrochloride capsule can effectively relieve the pain in patients with migraine, reduce the cerebral blood flow velocity, the efficacy is superior to simple flunarizine hydrochloride capsule.
Acupuncture Points ; Acupuncture Therapy ; Hemodynamics ; Humans ; Migraine Disorders/therapy* ; Pain ; Treatment Outcome

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Gloeostereum incarnatum has edible and medicinal value and was first cultivated and domesticated in China. We sequenced the G. incarnatum monokaryotic strain GiC-126 on an Illumina HiSeq X Ten system and obtained a 34.52-Mb genome assembly sequence that encoded 16,895 predicted genes. We combined the GiC-126 genome with the published genome of G. incarnatum strain CCMJ2665 to construct a genetic linkage map (GiC-126 genome) that had 10 linkage groups (LGs), and the 15 assembly sequences of CCMJ2665 were integrated into 8 LGs. We identified 1912 simple sequence repeat (SSR) loci and detected 700 genes containing 768 SSRs in the genome; 65 and 100 of them were annotated with gene ontology (GO) terms and KEGG pathways, respectively. Carbohydrate-active enzymes (CAZymes) were identified in 20 fungal genomes and annotated; among them, 144 CAZymes were annotated in the GiC-126 genome. The A mating-type locus (MAT-A) of G. incarnatum was located on scaffold885 at 38.9 cM of LG1 and was flanked by two homeodomain (HD1) genes, mip and beta-fg. Fourteen segregation distortion markers were detected in the genetic linkage map, all of which were skewed toward the parent GiC-126. They formed three segregation distortion regions (SDR1–SDR3), and 22 predictive genes were found in scaffold1920 where three segregation distortion markers were located in SDR1. In this study, we corrected and updated the genomic information of G. incarnatum. Our results will provide a theoretical basis for fine gene mapping, functional gene cloning, and genetic breeding the follow-up of G. incarnatum.

Objective: To explore the predictive value of neutrophil/lymphocyte ratio (NLR) on myocardial injury in severe COVID-19 patients. Methods: In this single-center retrospective cohort study, we collected and analyzed data form 133 severe COVID-19 patients admitted to Renmin Hospital of Wuhan University (Eastern District) from January 30 to February 18, 2020. Patients were divided into myocardial injury group (n=29) and non-myocardial injury group (n=104) according the presence or absence of myocardial injury. The general information of patients was collected by electronic medical record database system. All patients were followed up for 30 days, the organ injury and/or dysfunction were monitored, the in-hospital death was compared between the two groups, and the disease progression was reevaluated and classified at 14 days after initial hospitalization. Logistic regression analysis was performed to identify risk factors of myocardial injury in severe COVID-19 patients. The ROC of NLR was calculated, and the AUC was determined to estimate the optimal cut-off value of NLR for predicting myocardial injury in severe cases of COVID-19. Results: There was statistical significance in age, respiratory frequency, systolic blood pressure, symptoms of dyspnea, previous chronic obstructive pulmonary disease, coronary heart disease history, white blood cells, neutrophils, lymphocytes, platelets, C-reactive protein, platelet counting, aspartate transaminase, albumin, total bilirubin, direct bilirubin, urea, estimated glomerular filtration rate, total cholesterol, low-density lipoprotein cholesterol, D-dimer, CD3⁺, CD4⁺, partial pressure of oxygen, partial pressure of CO₂, blood oxygen saturation, other organ injury, clinical outcome and prognosis between patients with myocardial injury and without myocardial injury (all P<0.05). Multivariate logistic regression analysis showed that NLR was a risk factor for myocardial injury (OR=1.066，95%CI 1.021-1.111，P=0.033). ROC curve showed that NLR predicting AUC of myocardial injury in severe COVID-19 patients was 0.774 (95%CI 0.694-0.842), the optimal cut-off value of NLR was 5.768, with a sensitivity of 82.8%, and specificity of 69.5%. Conclusion: NLR may be used to predict myocardial injury in severe COVID-19 patients.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/pathology* ; Heart Diseases/virology* ; Humans ; Lymphocytes/cytology* ; Myocardium/pathology* ; Neutrophils/cytology* ; Pandemics ; Pneumonia, Viral/pathology* ; Prognosis ; ROC Curve ; Retrospective Studies ; SARS-CoV-2