Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

Osteoscarcopenia (OS) is a common degenerative syndrome in the elderly, which is caused by a decrease in both bone and muscle mass during the aging process, leading to osteoporosis and sarcopenia, a decrease in body balance, and a risk of falls and fractures, posing a serious threat to the quality of life and lifespan of the elderly. Osteoskeletal dystrophy increases with age, and its occurrence is higher in females than that in males. At present, there is no unified diagnostic standard, making it impossible to achieve early detection and intervention. The commonly used diagnostic methods include quantitative computed tomography (CT), magnetic resonance imaging (MRI), dual energy X-ray absorptiometry (DXA), muscle mass bioelectrical impedance analysis (BIA), as well as daily gait speed (UGS), short physical performance battery (SPPB), timed start test (TUG), and biochemical evaluation indicators to improve early diagnosis and screening. Due to the fact that both bones and muscles belong to the motor system, osteoporosis and sarcopenia share common pathogenic factors in genetics, endocrine, paracrine, and fat infiltration, which interact and regulate each other, inducing the occurrence of osteoscarcopenia. Osteoporosis and sarcopenia, two age-related diseases, share the same pathogenesis and regulatory pathways, as well as common drug targets. For example: somatostatin α‑actin-3, peroxisome proliferator activated receptor γ coactivation factor-1α (PGC-1α), myocyte enhancer factor-2 (MEF2C), sterol regulatory element binding transcription factor 1 (SREBF1), protoadhesion 7 (PCDH7) and methyltransferase like 21C (METTL21C), osteocalcin and bone derived bone factor gap junction connexin 43 (Cx43), growth hormone (GH), sex hormones, and diseases (such as tumors, diabetes, polycystic ovary syndrome, cardiovascular disease, anemia, disability, inflammatory disease), aging, nutrition, and poor living habits are closely related to osteosarcopenia. Osteoporosis is characterized by low bone mass and microstructural degeneration of bone tissue, while sarcopenia is characterized by loss of muscle mass, strength, and function, both of which often coexist in the elderly population. Exercise regulates muscle and skeletal cytokines such as myostatin (MSTN) and irisinβ‑aminoisobutyric acid (BAIBA), brain derived neutrophil factor (BDNF), interleukin, prostaglandin E2, Wnt, osteocalcin (OCN), and transforming growth factor‑β (TGF‑β) and receptor activator of NF-κB ligand (RANKL) interfere with each other to prevent and treat osteoscarcopenia. Wnt/β‑catenin signaling pathway can simultaneously regulate the growth and metabolism of bones and muscles, and promote osteoblast proliferation, maturation, and mineralization by increasing OPG/RANKL, which is beneficial for bone mass increase and induces proliferation of muscle satellite cells, stimulating and promoting increased muscle synthesis. NF‑κB pathway is the main regulatory factor for inflammation mediated muscle atrophy. Meanwhile, NF‑κB DNA can participate in RANKL inducing osteoclast differentiation in bone tissue, thereby reducing bone mass. Although exercise and nutrition can improve the symptoms of osteoporosis, they cannot be completely cured, and there are no specific drugs in clinical practice that can cure sarcopenia. Because osteoscarcopenia has a common crosstalk mechanism in the aging process, it is of great significance to prevent osteoscarcopenia by improving bone mass and muscle content through exercise, nutrition, and medication.

Objective To observe the clinical efficacy of Chang'an Juntai Granules(mainly composed of Pseudostellariae Radix,Atractylodis Macrocephalae Rhizoma,Poria,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Paeoniae Radix Alba,Saposhnikoviae Radix,Citri Reticulatae Pericarpium,Coptidis Rhizoma,and Aucklandiae Radix)in the treatment of diarrhea-predominant irritable bowel syndrome(IBS-D)with liver depression and spleen deficiency syndrome,and to evaluate its safety.Methods A single-center,randomized,double-blind,placebo-controlled clinical trial was designed.A total of 130 patients with IBS-D of liver depression and spleen deficiency were included.The patients were randomly divided into a treatment group and a control group by random number table method,with 65 cases in each group.The treatment group was treated with Chang'an Juntai Granules,and the control group was treated with Chang'an Juntai Placebo Granules.The course of treatment covered 12 weeks.The changes in the scores of IBS Symptom Severity Scale(IBS-SSS),Bristol Stool Form Scale(BSFS),IBS Quality of Life Questionnaire(IBS-QOL)and Hospital Anxiety and Depression Scale(HADS)in the two groups were observed before and after treatment.After treatment,the clinical efficacy and medication safety in the two groups were evaluated.Results(1)During the trial,six cases in the treatment group and eight cases in the control group fell off.Eventually,a total of 116 patients completed the clinical trial,including 59 cases in the treatment group and 57 cases in the control group.(2)After 12 weeks of treatment,the total effective rate of the treatment group was 88.14％(52/59),and that of the control group was 45.61％(26/57).The intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the treatment group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.01).(3)After treatment,the IBS-SSS scores of the two groups and the BSFS and IBS-QOL scores of the treatment group were significantly lower than those before treatment(P＜0.01),while the scores of Hospital Anxiety and Depression Scale-Anxiety subscale(HADA)and Hospital Anxiety and Depression Scale-Depression subscale(HADD)in the two groups and the BSFS and IBS-QOL scores in the control group showed no obvious changes(P＞0.05).Compared with the control group,the decrease of IBS-SSS,BSFS and IBS-QOL scores in the treatment group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(4)During the trial,no serious adverse reactions or adverse events occurred in the two groups,no drug-related abnormalities of liver and kidney function,blood,and heart function were found,either.Conclusion Chang'an Juntai Granules are effective on improving the clinical symptoms and fecal characteristics of IBS-D patients with liver depression and spleen deficiency syndrome,and on enhancing the quality of life of patients.The granules excert definite curative effect and high safety,and has certain value of clinical application.

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.

Objective:To explore the effect and safety of local spraying tranexamic acid after thyroidectomy.Methods:Randomized double-blind placebo-controlled study method was used. Sixty-four patients underwent scheduled thyroidectomy from December 2022 to August 2023 in Baotou Cancer Hospital were selected. The patients were divided into tranexamic acid group and control group by random digits table method with 32 cases each. Before closing the wound during surgery, 16 ml of tranexamic acid injection with concentration of 25 mg/ml was used to wash the wound and 1 ml of tranexamic acid injection (tranexamic acid 100 mg) used to locally spray in tranexamic acid group; 16 ml of the sterile water for injection was used to wash the wound and 1 ml of sterile water for injection was used locally spray in control group, and then the drainage tube was clipped for 20 min. The neck drainage volume on the first to fourth day after surgery and complication were recorded; the C-reactive protein level before and after surgery was detected.Results:Two patients in each group withdrew from the study midway. The drainage volume on the first, second and third day and total drainage volume in tranexamic acid group were significantly lower than those in control group: (29.10 ± 8.04) ml vs. (38.50 ± 8.67) ml, (18.00 ± 7.33) ml vs. (27.20 ± 10.66) ml, (10.70 ± 5.75) ml vs. (14.60 ± 6.83) ml and (69.20 ± 24.48) ml vs. (96.70 ± 31.90) ml, and there was statistical difference ( P<0.01); there was no statistical difference in the drainage volume on the fourth day after surgery between two groups ( P>0.05). There was no statistical difference in C-reactive protein before and after surgery between two groups ( P>0.05). There was 1 case of fever (body temperature 37.5 ℃) in the control group, and there were no complications such as intermuscular thrombosis, venous thrombosis, incision infection and delayed wound healing in both groups. Conclusions:Local application of tranexamic acid after thyroidectomy can reduce postoperative drainage volume and does not increase the risk of thrombosis, infection and delayed healing.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Objective To explore the application value of automatic cytomorphological analyzer in the morphological analysis of white blood cells(WBC)in peripheral blood.Methods A total of 306 venous blood samples from inpatients and outpatients were randomly selected and prepared with automatic cytomorphological analyzer for WBC pre-classification.The differences between automatic cytomorphological analyzer counting,automatic blood cell analyzer counting and manual counting were compared,and the correlation between automatic cytomorphological analyzer and manual counting method was analyzed.Results Compared with the other two methods,the automatic cytomorphologi-cal analyzer was able to detect more types of WBC,especially abnormal cells.There were no signifi-cant differences between automatic cytomorphological analyzer and manual counting method for 6 ma-ture WBC types(band neutrophils,segmented neutrophils,lymphocytes,monocytes,eosinophils,and basophils),immature cells at different stages and atypical lymphocyte counts(P＞0.05).Re-sults of the 6 mature WBC types counted by the automatic cytomorphological analyzer and manual counting had favorable correlations(r＞0.8).Conclusion The automatic cytomorphological analyzer can classify more types of WBC,provide WBC counting results that are highly consistent with manual microscopy,and the counting results of the two methods have a good correlation.

Objective To explore the application value of automatic cytomorphological analyzer in the morphological analysis of white blood cells(WBC)in peripheral blood.Methods A total of 306 venous blood samples from inpatients and outpatients were randomly selected and prepared with automatic cytomorphological analyzer for WBC pre-classification.The differences between automatic cytomorphological analyzer counting,automatic blood cell analyzer counting and manual counting were compared,and the correlation between automatic cytomorphological analyzer and manual counting method was analyzed.Results Compared with the other two methods,the automatic cytomorphologi-cal analyzer was able to detect more types of WBC,especially abnormal cells.There were no signifi-cant differences between automatic cytomorphological analyzer and manual counting method for 6 ma-ture WBC types(band neutrophils,segmented neutrophils,lymphocytes,monocytes,eosinophils,and basophils),immature cells at different stages and atypical lymphocyte counts(P＞0.05).Re-sults of the 6 mature WBC types counted by the automatic cytomorphological analyzer and manual counting had favorable correlations(r＞0.8).Conclusion The automatic cytomorphological analyzer can classify more types of WBC,provide WBC counting results that are highly consistent with manual microscopy,and the counting results of the two methods have a good correlation.

Objective: To investigate the repair effect and JNK/NF-κB,SOX9 mechanisms of vibration exercise with different frequencies on articular cartilage in rats with early knee osteoarthritis. Methods: Forty-eight adult male SD rats were randomly divided into six groups(n=8):model control group(MC),high frequency vibration group 1 (GP₁,60 Hz),high frequency vibration 2 group (GP₂,40 Hz),medium frequency vibration group (ZP,20 Hz),minor frequency group(DP,10 Hz)and normal control group(NC). Except for NC group,the rats in each group were made into early knee osteoarthritis model after six weeks of knee joint cavity injection of papain solution and 2% mixture l-cysteine on the 1^st,4 ^th and 7^th day. Each exercise group was subjected vibration to 40 minutes a day with amplitude of 2～5 mm and 5 days a week. Four weeks later, the articular cartilage of the lateral femoral condyle of the both back leg knee joints were detected by HE staining,serine O staining and Mankin scores for morphological observation. The expression levels of JNK,NF-κB p65 and Sox9 mRNA in articular cartilage of the medial femoral condyle were detected by RT-qPCR,and the protein expressions of JNK,NF-κB p65 and Sox9 were detected by Western blot. Results: Compared with the NC group,the Mankin score in other groups was significantly higher (P＜0.01). Compared with the MC group,the Mankin score of each vibration group was significantly lower(P＜0.05),the mRNA and protein expressions of JNK and NF-κB p65 in each vibration training group were significantly lower (P＜0.01),the expressions of Sox9 mRNA and protein in vibration training group were increased significantly (P＜0.01). Compared with the higher frequency group,the Mankin score,the mRNA and protein expressions of JNK and NF-κB p65 of lower frequency group were significantly lower (P＜0.05 or P＜0.01). But the expressions of Sox9 mRNA and protein were significantly higher (P＜ 0.05 or P＜0.01). Conclusion: Vibration exercise of different frequencies may present varying degrees of cartilage repair impact in rats with early knee osteoarthritis,and the cartilage repair by low-frequency vibration training is better than that by high-frequency vibration. This can be one of the mechanisms on controlling collagen synthesis by down-regulating JNK/NF-κB expression and increasing SOX9 activity of OA articular cartilage.
Animals ; Cartilage, Articular/metabolism* ; MAP Kinase Kinase 4 ; Male ; NF-kappa B/metabolism* ; Osteoarthritis, Knee/therapy* ; RNA, Messenger/metabolism* ; Rats ; Rats, Sprague-Dawley ; SOX9 Transcription Factor ; Vibration

Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.
Child ; Child, Preschool ; China ; Female ; Fibrinogen/chemistry* ; Humans ; Liver/pathology* ; Liver Diseases/pathology* ; Male ; Metabolic Diseases/pathology* ; Retrospective Studies