ObjectiveTo compare the contents and relative molecular weight distributions of proteins and polypeptides in Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules of Hirudo single medicinal preparations， to evaluate the in vitro anticoagulant， antiplatelet and fibrinolytic activities of the three preparations， and to investigate the effects of temperature， pH and digestive enzymes on the anticoagulant activities of the three preparations. MethodsThe contents of soluble proteins and polypeptides in the three preparations were determined by bicinchoninic acid assay（BCA） and Bradford method， and the relative molecular weight distributions of the three preparations were determined by electrophoresis combined with gel chromatography. The antithrombin activity of the three preparations was evaluated by fibrinogen-thrombin time（Fibg-TT） method， and their anticoagulant activities were further assessed by the elongations of activated partial thromboplastin time（APTT）， prothrombin time（PT） and thrombin time（TT）. The antiplatelet aggregation activities of the three preparations were measured by turbidimetry and the fibrinolytic activities were measured by fibrin plate method. Relative TT was used as index to investigate the effects of temperature， pH and digestive enzyme buffer on anticoagulant activities of the three preparations. ResultsAt the lowest single dosage， the contents of proteins and polypeptides were in the order of Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. Both Huoxue Tongmai capsules and Maixuekang capsules had 11 electrophoretic bands between 4.0 kDa and 90 kDa， the bands of Maixuekang capsules were more clear in the range of >25 kDa， and there was 1 obvious band at 14 kDa for the two capsules. Huoxue Tongmai capsules had one specific band at 9.0 kDa and Maixuekang capsules had one specific band at 48.0 kDa. Naoxuekang dropping pills only had 2 electrophoretic bands at 6.5 kDa and 8.5 kDa， primarily containing peptides below 2 kDa， most of which were oligopeptides. The anticoagulant activity concentrations of the three preparations exhibited a certain dose-dependent effect. At the lowest single dosage， The anticoagulant activity concentrations were ranked as Naoxuekang dropping pills>Huoxue Tongmai capsules>Maixuekang capsules. The prolongation effect of the three preparations on coagulation time was dose-dependent. At the same concentration， the prolongation effect of Naoxuekang dropping pills and Huoxue Tongmai capsules was APTT prolongation rate>TT prolongation rate>PT prolongation rate， whereas for Maixuekang capsules， the sequence was TT prolongation rate>APTT prolongation rate>PT lengthening rate. At the single minimum dosage， the order of APTT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules≈Naoxuekang dropping pills， the order of PT prolongation rate was Naoxuekang dropping pills≈Maixuekang capsules>Huoxue Tongmai capsules， and the order of TT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. The three preparations showed dose-dependent effects on platelet aggregation induced by adenosine diphosphate（ADP） and arachidonic acid（AA）， and the effect induced by ADP was stronger than that induced by AA. The anti-platelet aggregation effect of Naoxuekang dropping pills was significantly stronger than that of Maixuekang capsules（P<0.01）， whereas Huoxue Tongmai capsules had the effect of promoting platelet aggregation. None of the three preparations had the ability to dissolve fibrin. The anticoagulant activity of Naoxuekang dropping pills was least affected by heating， while the activities of the two capsules decreased significantly within 5 min above 80 ℃， and continued to decrease within 2 h. Compared with pure water， the anticoagulant activities of the three preparations could be increased by 1-3 times under strong acidity（pH 1-3）. In the pepsin buffer， the anticoagulant activity of Naoxuekang dropping pills could be increased by 1-3 times， while the anticoagulant activities of Huoxue Tongmai capsules and Maxuekang capsules were significantly decreased， the lowest levels were about 60% and 20%， respectively. In trypsin buffer， the anticoagulant activities of Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules decreased significantly， and the lowest levels decreased to about 41%， 41% and 35%， respectively. ConclusionThe contents of proteins and polypeptides and relative molecular weights of the preparations derived from lyophilized fresh Hirudo powder， dried Hirudo powder and reflux extract of Hirudo decrease sequentially， and the anticoagulant activity decrease gradually， but the anticoagulant pathway is different. And the anti-platelet aggregation activity of the reflux extract is significantly enhanced. The heat resistance and gastrointestinal stability of the three preparations increase successively， and the first two are suitable for enteric-soluble preparations， while the latter is suitable for routine oral administration. The above results can provide data reference for the rationality of different preparation methods， active substances， pharmacodynamics and mechanism of Hirudo preparations.

Objective:To construct an early rehabilitation management model for postoperative kinesiophobia patients after total knee arthroplasty (TKA) based on a topic-oriented quality control circle method, aiming to improve the quality of early rehabilitation management.Methods:Using a convenience sampling method, 120 TKA patients with kinesiophobia treated in the Department of Orthopedics at the First Affiliated Hospital of Zhengzhou University from January to April 2022 and September to December 2022 were selected. The patients from January to April 2022 were set as the control group, and those from September to December 2022 were set as the observation group, with 60 patients in each group. The control group received routine rehabilitation management after TKA surgery, while the observation group received the early rehabilitation management model based on the 10 steps of the topic-oriented quality control circle (topic selection, activity planning, clarification of the topic, goal setting, countermeasure formulation, pursuit of optimal strategies, etc.) in addition to the routine management. The differences between the two groups were compared in terms of kinesiophobia score, knee function score, pain score, early rehabilitation assessment rate, effective analgesia rate, and 24-hour ambulation rate.Results:After the intervention, the observation group showed significantly lower knee pain scores (2.89±0.66) and kinesiophobia scores (23.27±4.87) compared to the control group, with a significantly higher knee function score (74.47±7.40), all differences were statistically significant (all P<0.01). Additionally, the observation group had a significantly higher early rehabilitation assessment rate, effective analgesia rate, 24-hour ambulation rate, early rehabilitation compliance rate, earlier time for the first ambulation, shorter hospital stay, and reduced costs compared to the control group, with all differences showing statistical significance (all P<0.01) . Conclusions:The application of the topic-oriented quality control circle to construct and implement an early rehabilitation management model for postoperative kinesiophobia patients after TKA can effectively improve the quality of early rehabilitation management, reduce kinesiophobia levels, enhance knee joint function, and alleviate the economic burden.

Objective:To construct an early rehabilitation management model for postoperative kinesiophobia patients after total knee arthroplasty (TKA) based on a topic-oriented quality control circle method, aiming to improve the quality of early rehabilitation management.Methods:Using a convenience sampling method, 120 TKA patients with kinesiophobia treated in the Department of Orthopedics at the First Affiliated Hospital of Zhengzhou University from January to April 2022 and September to December 2022 were selected. The patients from January to April 2022 were set as the control group, and those from September to December 2022 were set as the observation group, with 60 patients in each group. The control group received routine rehabilitation management after TKA surgery, while the observation group received the early rehabilitation management model based on the 10 steps of the topic-oriented quality control circle (topic selection, activity planning, clarification of the topic, goal setting, countermeasure formulation, pursuit of optimal strategies, etc.) in addition to the routine management. The differences between the two groups were compared in terms of kinesiophobia score, knee function score, pain score, early rehabilitation assessment rate, effective analgesia rate, and 24-hour ambulation rate.Results:After the intervention, the observation group showed significantly lower knee pain scores (2.89±0.66) and kinesiophobia scores (23.27±4.87) compared to the control group, with a significantly higher knee function score (74.47±7.40), all differences were statistically significant (all P<0.01). Additionally, the observation group had a significantly higher early rehabilitation assessment rate, effective analgesia rate, 24-hour ambulation rate, early rehabilitation compliance rate, earlier time for the first ambulation, shorter hospital stay, and reduced costs compared to the control group, with all differences showing statistical significance (all P<0.01) . Conclusions:The application of the topic-oriented quality control circle to construct and implement an early rehabilitation management model for postoperative kinesiophobia patients after TKA can effectively improve the quality of early rehabilitation management, reduce kinesiophobia levels, enhance knee joint function, and alleviate the economic burden.

Objective·To explore the correlation between the genetic variations rs7305526 and rs11615756 of nitric oxide synthase 1(NOS1)and the human sleep traits,including insomnia,sleep duration,and clinical quantitative traits related to obstructive sleep apnea(OSA).Methods·The NOS1 gene expression pattern at the whole-brain level using the Allen Human Brain Atlas dataset was analyzed.Subsequently,we performed expression quantitative trait locus(eQTL)analysis to investigate the impact of rs7305526 and rs11615756 on NOS1 gene expression.Regression analysis was conducted to assess the associations between rs7305526 and rs11615756 with insomnia and sleep duration based on the United Kingdom Biobank(UKB)Genome-Wide Association Study(GWAS)dataset.Furthermore,we explored the relationships between rs7305526 and rs11615756 with clinical quantitative traits of OSA,such as respiratory events,oxygen levels,and sleep traits,using clinical monitoring data from the Shanghai Sleep Health Study Cohort(SSHS)based on standard polysomnography(PSG).Results·The NOS1 gene demonstrated elevated levels of expression in various brain regions crucial for regulating sleep,namely the amygdala,basal forebrain,striatum,and thalamus,as well as in the respiratory center,including the mesencephalon and pontine tegmentum.In contrast,the expression level of NOS1 gene was significantly reduced or absent in areas such as the cerebral cortex and cerebellum.Variants rs7305526 and rs11615756 were significantly negatively correlated with the expression levels of NOS1 in the cerebral cortex.Additionally,rs11615756 was also significantly negatively correlated with the expression level of NOS1 in the amygdala.Analysis of the UKB GWAS data revealed that the variant rs7305526 was not significantly associated with either insomnia or sleep duration,while rs11615756 demonstrated a noteworthy negative correlation specifically with sleep duration.Data obtained from the SSHS indicated a significant association between rs7305526 and alterations in clinical quantitative traits of OSA,including lowest pulse blood oxygen saturation(LSpO2),apnea-hypopnea index(AHI),and the ratio of non-rapid eye movement(NREM)stage 2 sleep duration.Although rs11615756 showed a notable negative correlation solely with the quantity of NREM stages 2 and 3,both rs11615756 and rs7305526 showed significant correlations with some respiratory events and oxygen traits after stratification according to the severity of OSA.Conclusion·Genetic variants of NOS1 gene are respectively associated with human sleep duration traits and OSA-related variables,suggesting that NOS1 gene plays a crucial regulatory role in human sleep and clinical quantitative traits of OSA.The regulation of sleep traits by rs7305526(C>A)is independent of its regulation of respiratory events and oxygen traits.

Objective·To explore the correlation between the genetic variations rs7305526 and rs11615756 of nitric oxide synthase 1(NOS1)and the human sleep traits,including insomnia,sleep duration,and clinical quantitative traits related to obstructive sleep apnea(OSA).Methods·The NOS1 gene expression pattern at the whole-brain level using the Allen Human Brain Atlas dataset was analyzed.Subsequently,we performed expression quantitative trait locus(eQTL)analysis to investigate the impact of rs7305526 and rs11615756 on NOS1 gene expression.Regression analysis was conducted to assess the associations between rs7305526 and rs11615756 with insomnia and sleep duration based on the United Kingdom Biobank(UKB)Genome-Wide Association Study(GWAS)dataset.Furthermore,we explored the relationships between rs7305526 and rs11615756 with clinical quantitative traits of OSA,such as respiratory events,oxygen levels,and sleep traits,using clinical monitoring data from the Shanghai Sleep Health Study Cohort(SSHS)based on standard polysomnography(PSG).Results·The NOS1 gene demonstrated elevated levels of expression in various brain regions crucial for regulating sleep,namely the amygdala,basal forebrain,striatum,and thalamus,as well as in the respiratory center,including the mesencephalon and pontine tegmentum.In contrast,the expression level of NOS1 gene was significantly reduced or absent in areas such as the cerebral cortex and cerebellum.Variants rs7305526 and rs11615756 were significantly negatively correlated with the expression levels of NOS1 in the cerebral cortex.Additionally,rs11615756 was also significantly negatively correlated with the expression level of NOS1 in the amygdala.Analysis of the UKB GWAS data revealed that the variant rs7305526 was not significantly associated with either insomnia or sleep duration,while rs11615756 demonstrated a noteworthy negative correlation specifically with sleep duration.Data obtained from the SSHS indicated a significant association between rs7305526 and alterations in clinical quantitative traits of OSA,including lowest pulse blood oxygen saturation(LSpO2),apnea-hypopnea index(AHI),and the ratio of non-rapid eye movement(NREM)stage 2 sleep duration.Although rs11615756 showed a notable negative correlation solely with the quantity of NREM stages 2 and 3,both rs11615756 and rs7305526 showed significant correlations with some respiratory events and oxygen traits after stratification according to the severity of OSA.Conclusion·Genetic variants of NOS1 gene are respectively associated with human sleep duration traits and OSA-related variables,suggesting that NOS1 gene plays a crucial regulatory role in human sleep and clinical quantitative traits of OSA.The regulation of sleep traits by rs7305526(C>A)is independent of its regulation of respiratory events and oxygen traits.

Objective:To investigate the effects of micro video combined with situational experience health education program in elderly diabetic patients.Methods:Totally, 100 elderly diabetic patients were enrolled from January to December in 2018 in Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine. They were assigned to experimental group ( n=50) and control group( n=50) by random number table. The control group received routine health education, while the experimental group received micro video combined with situational experience health education program. The intervention effects were assessed by Chinese version of Tilburg Frailty Indicator and Summary of Diabetes Self Care Action. Results:Finally, 45 cases were included in the experimental group and 47 cases in the control group. There was no significant difference between the two groups before intervention ( P>0.05). After intervention, the scores of physical frailty, psychological frailty, social frailty and total frailty were (2.60 ± 1.19) points, (1.24 ± 0.87) points, (1.11 ± 0.83) points and (4.96 ± 1.76) points in the experimental group, significantly lower than in the control group (3.45 ± 1.18) points, (1.96 ± 0.86) points, (2.06 ± 0.79) points and (7.47 ± 1.57) points. The difference was statistically significant ( t values were 3.32-7.23, P<0.01); the scores of diet, exercise, blood glucose monitoring, medication, foot care dimension and total self-care activities were (20.36 ± 2.22) points, (12.02 ± 2.33) points, (5.07 ± 0.81) points, (9.98 ± 1.99) points, (7.53 ± 1.10) points and (54.96 ± 4.49) points in the experimental group, significantly higher than in the control group (18.96 ± 2.12) points, (10.47 ± 2.24) points, (3.85 ± 0.83) points, (8.62 ± 1.69) points, (6.60 ± 1.12) points and (48.49 ± 4.07) points. the difference was statistically significant ( t values were 3.10-7.25, P<0.01). Conclusions:Micro video combined with situational experience can improve frailty status and self-care activities in elderly patients with diabetes.

Objective:To observe the dynamic changes of serum RANTES during the treatment with nucleos(t)ide analogues combined with pegylated interferon alpha (peginterferon-α), and further analyze the predictive effect of RANTES on HBsAg clearance in patients with chronic hepatitis B.Methods:98 cases of chronic hepatitis B with quantitative HBsAg < 3 000 IU/ml and HBV DNA < 20 IU/ml after≥1 year NAs treatment were enrolled. Among them, 26 cases continued to receive NAs monotherapy, 72 cases received NAs combined with pegylated interferon alpha therapy. The changes in RANTES during treatment were observed. The receiver operating characteristic curve was used to analyze the early changes of RANTES to predict the HBsAg clearance during 48 weeks.Results:During 48 weeks, 15 cases (20.83%) had achieved HBsAg clearance in combination group, while no patient had achieved HBsAg clearance in NAs group. The overall serum RANTES level had decreased from baseline in NAs and combination group. At week 48, in the combination group, the serum RANTES level was decreased more significantly in patients with HBsAg clearance than patients without. Further analysis showed that, in combination group, HBsAg clearance rate of patients with serum RANTES decreased at week 12 and 24 was higher than patients with elevated (29.17% vs. 4.17%, P = 0.014; 28.00% vs. 4.55%, P = 0.052), and quantitative HBsAg reduction was larger significantly [(1.49 ± 1.26) log 10IU/ml vs. (0.73 ± 0.81) log 10IU/ml, P = 0.017; (1.54 ± 1.27) log 10IU/ml vs. (0.57 ± 0.56) log 10IU/ml, P = 0.004]. Receiver operating characteristic curve analysis showed that the baseline quantitative HBsAg and the reduction in quantitative HBsAg and serum RANTES during the early period were predictors of HBsAg clearance after 48-week combination therapy. Furthermore, the combination of baseline quantitative HBsAg and 12 - or 24-week reduction of serum RANTES were better predictors of HBsAg clearance than that of baseline quantitative HBsAg combined with HBsAg decrease at week 12 or 24. The area under the receiver operating characteristic curve of the former was 0.925 and 0.939, while that of the latter was 0.909 and 0.929, respectively. Conclusion:Early reduction of serum RANTES at week 12 and 24 can predict HBsAg loss in CHB patients receiving addition of peginterferon-α to ongoing NAs Therapy, so serum RANTES could be one of the key immunological markers for predicting HBsAg clearance.

Objective To investigate the effect of laparoscopic salpingotomy with suturing on prognosis of patients.Methods One hundred and thirty two cases patients of laparoscopic salpingotomy and embryo extraction in our hospital from October 2015 to Febrary 2017 were were divided into observation group (68 cases) with suturing and control group (64 cases) without suturing according to the operation procedure.The patency of fallopian tube was observed at 3 months after operation and the intrauterine gestation rate and recurrent ectopic pregnancy rate were observed 1 years after operation in two groups.Results The fallopian tube patency in the observation group and the control group was 58 cases (85.3％) and 39 cases (60.9％) respectively at 3 months after operation.7 cases (10.3％) and 12 cases(18.8％) of the fallopian tube were not smooth in the observation group and the control group respectively at 3 months after operation.The fallopian tube obstruction in the observation group and the control group was 3 cases (4.4％) and 13 cases (20.3％) respectively at 3 months after operation.The patency rate of fallopian tube in the observation group was higher than that in the control group (Z =6.215,P ＜ 0.05).The intrauterine gestation rate (69.1％ (47/68)) in the observation group was significantly higher than that in the control group (37.5％(24/64)) 1 years after operation and the difference between the two groups was statistically significant (x2 =5.41,P ＜0.05).The rate of recurrent ectopic pregnancy in the observation group (10.3％(7/68)) was significantly lower than that in the control group (26.6％(17/64)) and the difference between the two groups was statistically significant (x2 =4.826,P ＜ 0.05).Conclusion The laparoscopic salpingotomy with suturing can improve the patency rate of the fallopian tube and the rate of intrauterine gestation and reduce the rate of recurrent ectopic pregnancy in the patients after the operation.

OBJECTIVETo explore the effect of acupuncture and moxibustion on severe obesity complicated with hyperlipidemia in different genders and their comprehensive effect, lipid indexes, and obesity indexes.

METHODSA total of 264 patients of severe obesity complicated with hyperlipidemia were assigned into a male group (106 cases) and a female group (158 cases)．According to their clinical symptoms and patterns, acupuncture and moxibustion differentiation therapies were applied for stomach and intestine heat type, spleen deficiency and dampness resistance type, phlegm-dampness internal resistance type, liver depression and spleen deficiency type, spleen and kidney deficiency type and deficiency and blood stasis type．The obesity indexes were weight (W), obesity degree (A), body mass index (BMI) and body fat percentage (F); the blood lipid indexes were total cholesterol (TC)，triglyceride (TG)，low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C). The comprehensive effect, obesity and blood lipid indexes were observed．.

RESULTSThe total effective rate of the male group was 91.5% (97/106), and the total effective rate of the female group was 85.4% (135/158) , without statistical significance (>0.05). After treatment, the obesity indexes of W, A, BMI and F and the blood lipid levels of TC, TG, LDL-C decreased, the levels of HDL-C increased compared with those before treatment in the two groups (<0.05, <0.01). The different values before and after treatment of the above all indexes in the male group were higher than those in the female group (all <0.05).

CONCLUSIONAcupuncture and moxibustion can both improve the obesity and blood lipid indexes for the patients with obesity complicated with hyperlipidemia. The effect is better for male than for female. The methods can prevent and treat hyperlipidemia.

Objective: To investigate the clinical application and effect evaluation of failure mode and effect analysis (FMEA) in the optimization of vascular recanalization in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 389 STEMI patients admitted to the emergency department of the Fifth Central Hospital in Tianjin from January 2014 to January 2015 were served as the control group, and 398 STEMI patients admitted to the chest pain center of the Fifth Central Hospital in Tianjin from January 2016 to October 2017 were served as the experimental group. In the control group, routine emergency treatment was used. At the same time, the intervention room was 24-hour prepared for emergency vascular recanalization. The experimental group used FMEA. Through the usage of FMEA, the main factors those caused the delay in revascularization treatment were determined, and the revascularization process was optimized for these influencing factors, thereby shortening the "criminal" blood vessel opening time of patients. The door-to-balloon dilatation time (D-to-B time), troponin testing time, placement time of the catheterization room, initiation of the catheterization room to balloon dilatation time, and preoperative and 1 week postoperative N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, heart function parameters [left ventricular ejection fraction (LVEF), left ventricular short axis shortening rate (FS), left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD)] within 1 week, 3 months and 6 months after intervention, and the incidence of main cardiovascular adverse events within 1 month after intervention, hospital mortality, the length of hospital stay, and readmission within 1 year in the patients of two groups were recorded. Results: D-to-B time (minutes: 70.6±3.6 vs. 79.4±8.7), troponin testing time (minutes: 17.1±2.3 vs. 65.2±6.5), placement time of the catheterization room (minutes: 28.9±9.8 vs. 52.3±12.2) and activation of the catheterization room to balloon expansion time (minutes: 47.3±9.3 vs. 65.1±7.2) in the experimental group were significantly shorter than those in the control group (all P < 0.01). The NT-proBNP levels at 1 week after intervention in the two groups were lower than the preoperative levels, slightly lower in the experimental group, but the difference was not statistically significant. There was no significant difference in cardiac function at 1 week and 3 months after intervention between the two groups. The LVEF and FS at 6 months after intervention in the experimental group were significantly higher than those in the control group [LVEF: 0.622±0.054 vs. 0.584±0.076, FS: (38.1±4.3)% vs. (35.4±6.2)%, both P < 0.01], and LVESD and LVEDD were decreased significantly [LVESD (mm): 31.2±3.8 vs. 34.7±4.2, LVEDD (mm): 49.2±5.3 vs. 52.4±5.6, all P < 0.01]. The length of hospital stay in the experimental group was significantly shorter than that in the control group (days: 8.3±3.2 vs. 13.2±6.8, P < 0.01), the incidence of major cardiovascular adverse events within 1 month after intervention [13.6% (54/398) vs. 19.8% (77/389)], hospital mortality [1.8% (7/398) vs. 4.9% (19/389)], and readmission rate within 1 year [9.5% (38/398) vs. 14.5% (56/389)] in the experimental group were significantly lower than those in the control group (all P < 0.05). Conclusion The usage of FMEA to optimize the vascular recanalization procedure can shorten the emergency treatment time of STEMI patients, reduce the occurrence of adverse events, and improve the prognosis.