Zhejiang Chinese Medical University Research Articles

An Apriori Algorithm-Based Association Analysis of Analgesic Drugs in Chinese Medicine Prescriptions Recorded From Patients With Rheumatoid Arthritis Pain.

Chronic pain, a common symptom of people with rheumatoid arthritis, usually behaves as persistent polyarthralgia pain and causes serious damage to patients' physical and mental health. Opioid analgesics can lead to a series of side effects like drug tolerance and addiction. Thus, seeking an alternative therapy and screening out the corresponding analgesic drugs is the key to solving the current dilemma. Traditional Chinese Medicine (TCM) therapy has been recognized internationally for its unique guiding theory and definite curative effect. In this study, we used the Apriori Algorithm to screen out potential analgesics from 311 cases that were treated with compounded medication prescription and collected from “Second Affiliated Hospital of Zhejiang Chinese Medical University” in Hangzhou, China. Data on 18 kinds of clinical symptoms and 16 kinds of Chinese herbs were extracted based on this data mining. We also found 17 association rules and screened out four potential analgesic drugs—“Jinyinhua,” “Wugong,” “Yiyiren,” and “Qingfengteng,” which were promised to help in the clinical treatment. Besides, combined with System Cluster Analysis, we provided several different herbal combinations for clinical references.

Mid-term prognosis of the stromal vascular fraction for knee osteoarthritis: a minimum 5-year follow-up study

BackgroundThe short-term safety and efficacy of stromal vascular fraction (SVF) in treating knee osteoarthritis (KOA) have been extensively studied but the mid-term and long-term prognoses remain unknown.Methods126 KOA patients were recruited and randomly assigned to SVF group and hyaluronic acid (HA) group (control group). The scores of visual analogue scale (VAS) and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were assessed and compared between the two groups 1, 2, 3, and 5 years after treatment. The endpoint was defined as surgeries related to KOA or clinical scores exceeding the patient acceptable symptom state (PASS).ResultsThe VAS and WOMAC scores in the SVF group were significantly better than those in the HA group during the 5-year follow-up after treatment. The average responsive time to SVF treatment (61.52 months) was significantly longer than HA treatment (30.37 months). The adjusted Cox proportional hazards model showed that bone marrow lesion (BML) severity, body mass index (BMI) and treatment were independent risk factors and that the use of SVF reduced the risk of clinical failure by 2.602 times. The cartilage volume was reduced in both the SVF and control groups at 5 years but reduced less in the SVF group.ConclusionsUp to 5 years after SVF treatment, acceptable clinical state was present for approximately 60% of patients. BML severity and BMI were independent predictors of the prognosis.Trial Registry: This study was retrospectively registered at Chinses Clinical Trial Registry with identifier ChiCTR2100052818 and was approved by ethics committee of the First Affiliated Hospital of Zhejiang Chinese Medical University, number 2013-X-063.

Yunpi Qufeng Chushi Formula for Pre-Rheumatoid Arthritis: Study Protocol for a Multiple-Center, Double-Blind, Placebo-Controlled Randomized Controlled Trial.

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive bone erosion on diarthrodial joints. RA patients usually experienced three stages before final diagnosis: the health period, the pre-clinical period (immune response exists without clinical symptoms), and the pre-RA period (immune response exists with mild inflammatory manifestation). Presently, there is seldom guidance referring to early intervention which is a benefit for stable disease conditions and low morbidity. Prophylactic treatment is a major feature of traditional Chinese medicine (TCM). In this present study, a multi-center, double-blind, placebo-controlled clinical trial is carried out to evaluate both efficacy and safety in preventing RA progression on Yunpi Qufeng Chushi formula (YQCF). Method: The multi-center, double-blind, placebo-controlled clinical trial is conducted in 13 hospitals nationwide. A total of 390 patients ages between 18 and 70 will be recruited in the trial. They will be randomly assigned to the intervention group (YQCF) and placebo group. The follow-up visit will be taken every 3 months from baseline to 1 year. Diagnosis, disease activity scores, clinical disease activity index (CDAI), simplified disease activity index (SDAI), TCM syndrome scores, and safety assessments will be recorded at every visit. Joint color doppler ultrasound, health assessment questionnaire-disability index (HAQ-DI), and functional assessment of chronic illness therapy-fatigue (FACIT-F) will be recorded at baseline and the last visit. Discussion: This work will provide evidence of YQCF in preventing RA progression. However, whether early intervention would benefit the controlling RA disease still needs a long-term follow-up. Ethics and dissemination: Protocol version 2 (201910-1). This research was approved by the medical ethics committee of Zhejiang Chinese Medical University (2019-045). Results will be published in a peer-reviewed academic journal. Trial registration numbers: http://www.chictr.org.cn/index.aspx, ChiCTR1900024166.

Effect of avatrombopag in the management of severe and refractory chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumors

Chemotherapy-induced thrombocytopenia (CIT) is a common complication in cancer patients, especially after multiple cycles of chemotherapy, which leads to the delayed treatment or reduced dosage. The treatment of CIT is limited for refractory and severe cases. Herein we reported a single-center study of avatrombopag, a type of thrombopoietin receptor agonist (TPO-RA), for the treatment of severe and refractory (S/R) CIT who failed from multi-line treatments. A total of 13 cancer patients with S/R CIT were enrolled at the First Affiliated Hospital of Zhejiang Chinese Medical University from September 2020 to February 2021. All the patients were administered oral avatrombopag at an initial dose of 60 mg/day, which could be decreased as needed, over a period of 8 weeks. Eight (8/13, 61.5%) patients responded to avatrombopag (with a platelet count ≥50 × 109/L and transfusion independent), with a median response time of 27.5 (11–50) days, and the median cumulative day of platelet response was 79 (20–167). Ten of 13 patients (76.9%) no longer required platelet transfusion at the study endpoint. The predictor of response was the level of hemoglobin (HB) at study entry, patients with an HB over 90 g/L achieved a response rate of 88.9%. In addition, platelet count showed 87.5% sensitivity and 100% specificity to predict the treatment response at a cutoff value of 25.5× 109/L at the end of the third week management. No drug-related side effects were noticed during administration. Our study showed that avatrombopag could be a novel and effective drug for the treatment of severe and refractory CIT, especially for those with hemoglobin above 90 g/L. This study was registered at chictr.org.cn as # ChiCTR2100050646.

Clinical effect of micturition interruption exercise on urinary incontinence after radical prostatectomy.

To explore the effectiveness of micturition interruption exercise in improving the incidence of urinary incontinence after radical prostatectomy. With a retrospective case-control study, 96 patients admitted in the Second Affiliated Hospital of Zhejiang Chinese Medical University from August 2014 to August 2020 and underwent radical prostatectomy were collected as the subjects. Those patients who used micturition interruption exercise (n = 48) were set as the therapy group, and the control group was collected according to the ratio of 1:1; the patients used Kegel exercise (n = 48) to compare the rehabilitation of urinary incontinence in patients and the effect of training compliance on rehabilitation. The recovery time of urinary incontinence in the therapy group was significantly shorter than that of the control group. In the therapy group, 83.3% of patients with training compliance reached an average or above, while the control group only accounted for 58.3%. International Consultation on Incontinence Questionnaire Short-Form score of the therapy group was lower than that of the control group after surgery. Spearman analysis suggests that there is a negative correlation between the postoperative urinary incontinence recovery time and compliance with the micturition interruption exercise. Micturition interruption exercise could not only improve the compliance of patients with exercise, but also significantly shorten the recovery time of urinary incontinence after radical prostatectomy.

Efficacy analysis of Cheng's GIRAFFE reconstruction after proximal gastrectomy for adenocarcinoma of esophagogastric junction.

Reconstruction of the digestive tract for adenocarcinoma of esophagogastric junction (AEG) is in dispute. This study evaluated Cheng's gastric tube interposition esophagogastrostomy with reconstruction of His angle and fundus (Cheng's GIRAFFE anastomosis) in laparoscopic/open proximal gastrectomy for Siewert type II AEG, which was performed at Zhejiang Cancer Hospital and the First Affiliated Hospital of Zhejiang Chinese Medical University. Here, we discuss the preliminary results of gastric emptying and anti-reflux. From a retrospective database, 74 patients with advanced Siewert type II AEG underwent curative proximal gastrectomy with GIRAFFE anastomosis, and their gastric emptying and anti-reflux outcomes were evaluated by the Reflux Disease Questionnaire (RDQ) score, nuclide gastric emptying, 24-h impedance-pH monitoring and gastroscopy. Seventy-four patients successfully completed proximal partial gastrectomy with Cheng's GIRAFFE esophagogastric anastomosis. RDQ score six months after the operation was 2.2±2.5. Results of nuclide gastric emptying examinations showed that the gastric half-emptying time was 67.0±21.5 min, the 1-h residual rate was (52.2±7.7)%, the 2-h residual rate was (36.4±5.1)%, and the 3-h residual rate was (28.8±3.6)%; 24-h impedance-pH monitoring revealed that the mean DeMeester score was 5.8±2.9. Reflux esophagitis was observed by gastroscopy in 7 patients six months after surgery. Cheng's GIRAFFE anastomosis is safe and feasible for Siewert type II AEG.

Treatment Effects of Integrated TCM and Western Medicine Treatment Scheme on COVID-19: A Single-armed Clinical Trial.

BackgroudThe outbreak of COVID-19 has brought unprecedented perils to human health and raised public health concerns in more than two hundred countries. Safe and effective treatment scheme is needed urgently.ObjectiveTo evaluate the effects of integratedTCM and western medicine treatment scheme on COVID-19.MethodsA single-armed clinical trial was carried out in Hangzhou Xixi Hospital, an affiliated hospital with Zhejiang Chinese Medical University. 102 confirmed cases were screened out from 725 suspected cases and 93 of them were treated with integrated TCM and western medicine treatment scheme.Results83 cases were cured, 5 cases deteriorated, and 5 cases withdrew from the study. No deaths were reported. The mean relief time of fever, cough, diarrhea, and fatigue were (4.78 ± 4.61) days, (7.22 ± 4.99) days, (5.28 ± 3.39) days, and (5.28 ± 3.39) days, respectively. It took (14.84 ± 5.50) days for SARS-CoV-2 by nucleic acid amplification-based testing to turn negative. Multivariable cox regression analysis revealed that age, BMI, PISCT, BPC, AST, CK, BS, and UPRO were independent risk factors for COVID-19 treatment.ConclusionOur study suggested that integrated TCM and western medicine treatment scheme was effective for COVID-19.

Efficiency and safety of eltrombopag for multi-line failed Chinese patients with immune thrombocytopenia: cases with decreased megakaryocyte response well from single-center experience.

Immune thrombocytopenia (ITP) was defined using the International Consensus Guidelines as a platelet count <100×109/L in the absence of other causes or disorders that may be associated with thrombocytopenia. For patients without response to first-line treatment or refractory, TPO receptor agonist (RA) is an ideal choice. This study was to evaluate the efficiency and safety of eltrombopag for multi-line failed Chinese patients with immune thrombocytopenia (ITP) and analyze the possible factors that may contribute to the differences based on personal characteristics. Thirty-five multi-line failed ITP patients who received eltrombopag treatment were enrolled retrospectively at the First Affiliated Hospital of Zhejiang Chinese Medical University from January 2018 to August 2020. The general information, peripheral hemogram changes, count of bone marrow megakaryocyte (MK), peripheral T cell subsets were recorded, the response, and adverse effects, was evaluated. Results showed that the overall, complete, and partial response rates were 54.3% (n=19), 48.6% (n=17), and 5.7% (n=2) respectively to eltrombopag in our center. The overall response rate of patients with decreased MK was 70%, which was unexpectedly higher than that of the patient with increased or normal MK count (52.9% and 40%, respectively). For patients with poorer eltrombopag response group, more NK cells were found in peripheral blood, andthe patient with decreased MK have a higher level of T helper (Th) cells and regulatory T (Treg) cells. Nine eltrombopag-related adverse events were reported, and most commonly were upper respiratory tract infection (8.6%), elevated alanine transaminase (ALT, 5.7%), and venous thrombosis (5.7%). In conclusion, this study revealed that ITP patients with decreased megakaryocyte respond well to eltrombopag, and the abnormality of NK cells may play a role in patients with a poor eltrombopag response.

Effectiveness Between Daily and After-Each-Case Room Disinfection of the Endoscopy Unit.

Background: To evaluate the effectiveness between daily and after-each-case room disinfection in the endoscopy unit.Methods: This study was conducted in an endoscopy unit of the First Affiliation of Zhejiang Chinese Medical University. We cultured samples from the surface of endoscopy unit items, including operation unit air, isolation gown of an endoscopist, control panel buttons, workstation mouse, and the bed head of the patient. All the samples were divided into daily and after-each-case room disinfection groups. In addition, each group was subdivided into sedation and nonsedation gastroscopy with and without ventilation room groups.Results: The qualified rate of bed head samples of the patient were lower in the daily room disinfection group (76.67%) compared with the after-each-case group (100%). The isolation gown, mouse at the workstation, and the bed head of the patient demonstrated the lowest bacterial and fungal load in the after-each-case room disinfection group compared with the daily room disinfection group (p < 0.05). In the subgroup analysis, a higher microbial load was observed for the isolation gown of the endoscopist used during nonsedation gastroscopy in an unventilated room under the after-each-case room disinfection pattern (p < 0.05); a higher microbial load was observed for the control panel buttons used during nonsedation gastroscopy under the after-each-case room disinfection pattern (p < 0.05).Conclusions: For risk-free or low-risk patients, daily room disinfection provides the basic health requirements of the endoscopy procedure. However, it is better to adopt the after-each-case room disinfection for the isolation gown of the endoscopist and bed head of the patient. For the patients with high risk, the after-each-case room disinfection is more suitable for every endoscopy unit (www.ClinicalTrials.gov, NCT04399005).

Hp-Positive Chinese Patients Should Undergo Colonoscopy Earlier and More Frequently: The Result of a Cross-Sectional Study Based on 13,037 Cases of Gastrointestinal Endoscopy.

BackgroundIn China, the prevalence and mortality of colorectal cancer (CRC) have always been high, and more than 95% of CRC cases have evolved from colorectal polyps (CPs), especially adenoma. Early detection and treatment of CPs through colonoscopy is essential to reduce the incidence of CRC. Helicobacter pylori (Hp) is regarded as a risk factor for gastritis and gastric cancer and may also be a risk factor for CPs and CRC. However, few studies based on vast clinical cases exist in China to clarify whether Hp is a risk factor for CPs and CRC, and whether Hp-positive patients need to undergo colonoscopy checks earlier. This article attempts to make up for that deficiency.MethodThis cross-sectional study was conducted based on 13,037 patients without a treatment history of Hp who underwent their first gastroscopy and colonoscopy simultaneously at The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2018 to December 2019. Pearson χ2 test and logistic regression were used to determine whether Hp is a risk factor for CPs and CRC. Multifactor analysis of variance was used to define the impact of Hp on CPs prevalence with different ages, sexes.ResultsFor Chinese individuals, Hp is a risk factor for CPs and CRC. The odds ratio (OR) value are 1.228 (95% CI, 1.130 to 1.336) and 1.862 (95% CI 1.240-2.796), respectively. Hp-positive patients have a higher probability of multiple or large intestinal polyps. However, Hp infection does not increase the incidence of adenomas, nor does it affect the pathological type of adenomas. The OR of Hp on the risk of CPs was 1.432 (95%CI 1.275-1.608) for males but increased to 1.937 (95%CI 1.334-2.815) for those aged 35 to 40. For females, the results were similar.ConclusionsFor the Chinese, Hp is a risk factor for CPs and CRC (OR>1); the infection of Hp increased CPs risk in Chinese of all ages, especially aged 35-40, suggesting that Hp-positive patients should undergo colonoscopy frequently.

Development and analysis of clinical prediction model of acupuncture and moxibustion treatment for stroke at recovery stage

To develop the clinical prediction model of therapeutic effect in treatment with acupuncture and moxibustion for the patients with stroke at recovery stage under different conditions so as to provide a tool for predicting the therapeutic effect of acupuncture and moxibustion. A total of 1410 patients with stroke at recovery stage were collected from the Third Affiliated Hospital of Zhejiang Chinese Medical University from 2012 to 2019. The relevant data were extracted, i.e. sex, age, time of onset, neurological functional deficit score (NFDS) and acupuncture and moxibustion therapy. The difference of NFDS before and after treatment was adopted to evaluate the therapeutic effect in the patients. Using SPSS26.0 software and CART decision tree analysis, the clinical prediction model was developed. The key variables in the prediction model of therapeutic effect in the patients with stroke at recovery stage under different conditions included age, time of onset, hypertension, cardiac disease, diabetes, TCM diagnosis, hemoglobin (HB), serum homocysteine (HCY) and acupuncture and moxibustion therapy. There were 12 main rules generated by the decision tree model, including 8 rules for predicting the improvements of therapeutic effect and 4 rules for predicting the absence of improvements (i.e. no change and deterioration). The accuracy rates of the model training set and test set were 80.0% and 72.8% respectively, the area under curve (AUC) of ROC was 0.797 and the model identification and classification results were satisfactory. The clinical prediction model developed by CART decision tree analysis is high in accuracy for the prediction of the therapeutic effect in the patients with stroke at recovery stage under different conditions. Based on the therapeutic effect predicted in the hospital visit, the physicians may adopt the corresponding regimens of acupuncture and moxibustion therapy in patients.

Efficacy of Electroacupuncture Therapy in Patients With Postherpetic Neuralgia: Study Protocol for a Multicentre, Randomized, Controlled, Assessor-Blinded Trial.

Introduction: The efficacy of conventional treatments for treating postherpetic neuralgia (PHN) remains unsatisfactory. Thus, this multicentre, randomized controlled, assessor-blinded trial aims to investigate the efficacy and safety of electroacupuncture (EA) therapy in patients with PHN.Methods and Analysis: This multicentre randomized controlled trial will enroll 132 patients with PHN from 3 hospitals. All patients will be randomly assigned to either the EA combined with medication group or medication group through a computerized central randomization system in a 1:1 ratio. Outcome measures will be assessed before intervention, at 2, 4, 6 weeks after intervention and at the end of 8-week follow-up. Primary outcomes will be sensory thresholds and pain intensity. Secondary outcomes will include dosage of analgetic, quality of life, anxiety, and depression severity and sleep quality. All adverse effects will be assessed during the trial.Conclusions: This study will provide evidence to ascertain whether EA is effective and safe for treating PHN.Ethics and Dissemination: Ethics approval (No.ZSLL-KY-2017-025) has been obtained from the Ethics Committee of The Third Affiliated Hospital of Zhejiang Chinese Medical University. Informed consent will be signed prior to subject enrolment. The results will be submitted to international peer-reviewed journals and presented at international conferences.Trial Registration Number: The study protocol has been registered in the clinicaltrials registry with the identification code NCT04594226.

Rejuvenative Efficacy and NF-κB Pathway-Dependent Mechanism of Human Platelet Lysate on Skin Aging

Background: Skin aging is an irreversible process associated with poor self-regenerative capability. Human platelet lysate (hPL) contains rich amounts of growth factors, benefiting tissue regeneration. To explore the anti-aging efficacy and mechanism of hPL on skin, this study employed nude mice and human dermal fibroblasts (HDFs) to perform in vitro and in vivo assays. Methods: Flow cytometry and ELISA were conducted for quality control of hPL. In vivo, skin texture grading, histopathological observation, immunofluorescence analysis, and SOD and MDA assays were conducted to determine the effects of hPL on epidermis and dermis of aged skin. In vitro, senescence-associated-beta-galactosidase (SA-β-Gal) staining, CCK-8 and wound healing assays were conducted to respectively evaluate the effects of hPL on senescent HDFs. Real time PCR and western blot were conducted to clarify the molecular mechanism of hPL. Moreover, a retrospective analysis was conducted to determine hPL′s efficacy and safety in clinic. Findings: The in vivo data showed that hPL exerted pro-regenerative and anti-oxidative effects on aged skin, resulting in reversing aged skin state. The in vitro data showed that hPL significantly promoted the proliferation and migration of HDFs and suppressed the inflammation, SASP secretion and senescence state of senescent HDFs through regulation of NF-κB signaling pathway. The NF-κB pathway-dependent mechanism of hPL was positively verified by using P65 siRNA and negatively verified by using prostratin. In clinic, hPL obviously rejuvenated the skin appearances of subjects without any adverse event. Interpretation: This study provided novel knowledge of hPL, making it an ideal therapeutic for skin aging treatment. Funding Information: This work was supported by National Natural Science Foundation of China (Grant No. 81774331 and No. 81671926), Zhejiang Provincial Basic Public Welfare Research Program (Grant No. LGF18H110003), Zhejiang Provincial Natural Science Foundation of China (Grant No. LQ20H150008) and Hangzhou Science and Technology Development Program (Grant No. 20180533B38). Declaration of Interests: The authors have declared that no competing interest exists. Ethics Approval Statement: All blood specimens used in this study were approved by Ethical Committee of the Zhejiang Chinese Medical University. Informed consent was obtained from healthy adult donors. All mice were treated in strict accordance with the China legislation on the use and care of laboratory animals. All experiments on the mice were approved by the Medical Norms and Ethics Committee of Zhejiang Chinese Medical University (Approval number SYXK:2018-0012, Zhejiang, China).

Baicalein Binds to TLR4, Inhibits Colorectal Cancer Growth and Metastasis via the TLR4/HIF/VEGF Axis

Background: Lipopolysaccharide(LPS) inserts into the hydrophobic binding pocket of the myeloid differentiation protein 2(MD-2) that bound to toll-like receptor 4(TLR4). TLR4 antagonists have been designed based on the structure of lipid A, the innermost regions of LPS. However, these antagonists have poor bioavailability and may be toxic. Furthermore, the presence of lipid A moiety is not necessary for driving TLR4 activation. Therefore, compound directly binds to TLR4 is a better strategy to inhibit TLR4 activity. Methods: Biophysical techniques were used to examine the direct binding between baicalein and TLR4. With colorectal cancer(CRC) as models, coupled with drug-target-disease network, protein-protein interaction network and functional studies, the effect and the associated underlying mechanism of action upon the binding baicalein to TLR4 were examined. Findings: We evidently show a direct physical binding of baicalein to TLR4 in molecular docking, surface plasmon resonance biosensor analysis and bio-layer interferometry analysis. With CRC cells as model, we demonstrate the binding of baicalein to TLR4 with cellular thermal shift assay; which interrupts the binding of LPS to TLR4-MD-2 in the cells. Baicalein inhibits TLR4 activity, reduces CRC cell viability and migration in TLR4-dependent manner. Drug–targets–disease network and protein-protein interaction network highlight hypoxia inducible factor(HIF-1α) and vascular endothelial growth factor(VEGF) as downstream of TLR4, which are further validated in cell models. Involvement of TLR4/HIF-1α/VEGF axis in the anti-CRC and anti-angiogenic effect of baicalein is demonstrated in CRC-bearing mice and chick-chorioallantoic-membrane assay, respectively. Our study provides evidence to support the translation of baicalein into TLR4-targeting therapeutics. Funding Information: This work was partially supported by Research Grant Council of HKSAR HKBU-22103017-ECS, Innovation & Technology Commission #PRP/015/19FX, National Natural Science Foundation of China #SCM-2016-NSFC-003 and Natural Science Foundation of Guangdong Province #2018A0303130122 to HYK; the National Natural Science Foundation of China (82074019 and 81703705), Characteristic innovation projects of universities in Guangdong Province (2020KTSCX030), the Opening Project of Zhejiang Provincial Preponderant and Characteristic Subject of Key University (Traditional Chinese Pharmacology), Zhejiang Chinese Medical University (ZYAOX2018010) to ST. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: Animal experiments were approved by the Guangzhou University of Chinese Medicine Animal Care and Use Committee (Guangzhou, China), and conducted according to the ethical standards and national guidelines.

Effects of Guanxinshutong Capsules as Complementary Treatment in Patients With Chronic Heart Failure: Study Protocol for a Randomized Controlled Trial.

Chronic heart failure (CHF) is a common cardiovascular disease with high mortality and a poor prognosis, which places heavy burdens upon society and families. Traditional Chinese medicine (TCM) has been used extensively as complementary treatment for CHF. Guanxinshutong (GXST) capsules are used commonly for the treatment of coronary heart disease (CHD). Experimental research and small-sample clinical trials have shown that GXST can attenuate CHF. However, the effects of GXST as complementary medicine in CHF treatment lack high-quality clinical evidence. We have designed a multicenter, randomized, double-blind, placebo-controlled clinical trial that explores the efficacy and safety of using GXST compared with placebo for patients with CHF with reduced left ventricular ejection fraction (LVEF). A total of 480 participants will be assigned randomly to the GXST group or placebo group at a 2:1 ratio. GXST and placebo will be added to standard treatment for 12 weeks, and then followed up for another 40 weeks. The primary outcome is the improvement value of 6-min walk distance, and the secondary outcomes include plasma levels of N-terminal pro-B-type natriuretic peptide, New York Heart Association classification, Minnesota Living with Heart Failure Questionnaire scores, echocardiographic parameters, and clinical endpoint events. Adverse events will be monitored throughout the trial. Data will be analyzed following a predefined statistical analysis plan. This study will show the effects of the specific use of GXST in CHF patients with reduced LVEF. The Research Ethics Committee of the Second Affiliated Hospital of Zhejiang Chinese Medical University has approved this study (2019-Y-003-02). Written informed consent of patients will be required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR1900023877). Our results will be disseminated to the public through peer-reviewed journals, academic conferences, and the Internet.

Application of a multiple linear regression model of FEV1 in pulmonary function test

To construct a multiple linear regression model of forced expiratory volume in 1 second (FEV1) for estimating FEV1 in special populations unable to receive or uncooperative in pulmonary ventilation function tests. The multiple linear regression model of FEV1 was constructed based on the data of 813 individuals undergoing pulmonary function tests in First Affiliated Hospital of Zhejiang Chinese Medical University between September, 2017 and September, 2019, and was validated using the data of another 94 individuals from the same hospital between January and July, 2020. FEV1 of the individuals was measured by pulmonary ventilation function test, and respiratory resistance (Rrs) was measured using forced oscillation technique (FOT). Pearson correlation analysis was used to assess the correlation between the factors, and the model equation was established by multiple stepwise regression analysis. The calculated FEV1 based on the model was compared with the measured FEV1 among both the individuals included for modeling and validation. FEV1 was not significantly correlated with BMI (r=-0.026, P=0.457), poorly correlated with body mass (r=0.382, P=0.000), positively correlated with height (r=0.723, P=0.000), and negatively correlated with Rrs (r=-0.503, P=0.000) with an obvious gender differences (t=18.517, P=0.000). FEV1 was positively correlated with age among individuals below 25 years of age (r=0.578, P=0.000) and was negatively correlated with age among those beyond or at the age of 25 (r=-0.589, P=0.000). For individuals beyond or at the age of 25 years, the variables of height, gender, age and Rrs were included in the model, and the calculated FEV1 did not differ significantly from the measured values in either the modeling sample (n=751; t=1.293, P=0.196) or the verification sample (n=83;t=-1.736, P=0.086), and the two values were well correlated in the verification sample (r=0.891, P=0.000). For individuals below 25 years, only height was included in the model, and the calculated FEV1 and the measured values showed no significant difference in the modeling sample (n=62; t=-0.009, P=0.993) or the verification sample (n=11; t=-0.635, P=0.540) with a good correlation in the verification sample (r=0.795, P=0.003). The multiple linear regression model for calculating FEV1 constructed in this study is suitable for clinical application.

Seasonal Influenza Vaccine Hesitancy Profiles and Determinants Among Chinese Children's Guardians and the Elderly

Background: Seasonal influenza imposes a significant clinical and economic burden, yet vaccine coverage remains low in China due to possible influenza vaccine hesitancy (IVH) and practical issues. We sought to investigate IVH and its determinants among children’s guardians and the elderly for better understanding of the situation and for future intervention. Methods: We performed two cross-sectional studies to identify the profiles and determinants of IVH using stratified cluster random sampling in an eastern China province in 2019. Results: Of the 1,564 guardians and 522 elders, 43·2% (95%CI: 40·4–46·0%) of guardians and 33·5% of elders (95%CI: 29·5–37·6%) had IVH, whereas 31·3% of the guardians and 5·5% of the elderly had Influenza vaccine demand. ‘From rural area’ (Odds ratio: 1·36), ‘don’t know government recommendation for flu vaccination’ (1·39), ‘don’t know flu vaccine is vaccinated annually’ (1·93), ‘family members (0·22), friends and neighbors had positive attitude toward flu vaccine’(0·58) were related factors of the guardians’ IVH. ‘Aged 70–79 years’ (0·46), ‘had flu before’ (0·35), and ‘once had been vaccinated’ (0·42) were related to the elderly’s IVH. Interpretation: Poor awareness of influenza and vaccination, relatives’ negative/positive attitude, lack of government recommendations, anxiety about vaccine quality, and practical issues such as short supply are related to IVH in China. Precision education aiming hesitancy in wider groups are anticipated to increase vaccine confidence and coverage in influenza-vulnerable groups. Funding Statement: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Zhejiang Chinese Medical University Ethnics Committee reviewed and approved this protocol and informed consent was obtained from each subject.

Incidence and Disease Burden of Herpes Zoster in the Population Aged ≥50 Years in China: Data from an Integrated Health Care Network

Background: Herpes zoster (HZ) mainly affects elderly and immunocompromised individuals and is characterized by a painful vesicular rash. Data on the epidemiology of HZ, particularly in unvaccinated individuals aged ≥50 years, are still limited in China. Thus, this study aimed to evaluate the epidemiological features, disease burden, and associated risk factors of HZ in the population aged ≥50 years in China. Methods: We evaluated HZ patients who were aged ≥50 years between January 1, 2015 and December 31, 2017 in the electronic health record database of Yinzhou district. HZ and its complications were identified using ICD-10 codes. In addition, post-herpetic neuralgia (PHN) as a complication of HZ was defined as pain occurring or persisting 90 days after rash onset. The disease burden was estimated according to the duration of hospitalization, frequency of visits, pharmacological treatment cost, and examination cost. Cox proportional hazards regression was used to investigate the associated risk factors for HZ. Results: The overall incidence of HZ was 6.64 per 1000 person-years. Of the 4,313 initial episodes from 2015 to 2017, there were 99 recurrent cases. In total, 7.26% and 3.94% of the HZ patients had PHN and other complications, respectively. The average frequency of outpatient visits was significantly lower in patients with initial disease than that in patients with recurrence (3.6 vs. 6.7 per patient). The mean duration of hospital stay was longer in the recurrent episode than that in the initial episode (24.0 vs. 21.6 days). The inpatient and outpatient cost per new-onset HZ was approximately ¥8116.9 and ¥560.2 per patient, respectively. Age; female sex; suburban residency; and presence of immunocompromised disease, hypertension, or diabetes were significantly associated with the development of HZ. Conclusion: The incidence and recurrence rates of HZ showed different trends with increasing age. The presence of HZ-related complications increased the direct medical costs. Our findings help provide a basis for developing appropriate strategies for HZ prevention and control. Funding Statement: This study was supported by GlaxoSmithKline Biologicals SA (GSK study identifier: 212180). GlaxoSmithKline Biologicals SA provided the opportunity to review a preliminary version of this manuscript for factual accuracy, but the authors are solely responsible for final content and interpretation. The authors received no financial support or other forms of compensation related to the development of the manuscript. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Zhejiang Chinese Medical University Ethics Committee.

Clinical effect of one-stage total knee arthroplasty for knee osteoarthritis with femoral extra-articular deformity

Objective: To investigate the application and efficacy of the one-stage total knee arthroplasty (TKA) of intra-articular compensation osteotomy in knee osteoarthritis(KOA) patients with extra-articular deformity (EAD). Methods: A retrospective study of 9 patients with end-stage KOA and EAD undergoing one-stage TKA from January 2014 to December 2017 in the First Affiliated Hospital of Zhejiang Chinese Medical University was performed. There were 3 males and 6 females with an average age of 56 years(range, 19-77 years);5 cases of simple coronal deformity (varus 10°-27°, mean 18.2°), 3 cases of sagittal deformity (recurvatum15°-35°, mean 22.6°), 1 case combined with coronal and sagittal deformity (varus 16°, recurvatum 31°); hemophilia dysplasia in 1 case, fracture malformation in 8 cases. Main outcome measures included the mechanical axis, range of motion (ROM) and Hospital for Special Surgery Knee Score (HSS). Results: The mean follow-up period was 33.2 months (range, 25-47 months). The mechanical axis angle was restored from 12.4°±4.1°to 1.4°±0.9°(t=7.954, P<0.01). The HSS was improved from 28±14 preoperatively to 87±7 postoperatively (t=-11.174, P=0.013). The ROM increased from 56°±22°to 99°±8° (t=-5.480, P=0.010). There was no complications such as joint instability, infection, fracture, common peroneal nerve injury and early prosthesis loosening. Conclusions: For KOA patients with femoral EAD, one-stage TKA with intra-articular compensatory osteotomy can effectively restore the mechanical axis and obtain satisfying joint function. Through a series of measures such as preoperative measurement, soft tissue evaluation and 3D printing, the accuracy of surgery can be improved and the difficulty of surgery can be reduced.

Investigation of Invigorating Qi and Activating Blood Circulation Prescriptions in Treating Qi Deficiency and Blood Stasis Syndrome of Ischemic Stroke Patients: Study Protocol for a Randomized Controlled Trial.

Ischemic stroke (IS) is characterized by high morbidity and high mortality. The integration of Traditional Chinese medicine (TCM) and western medicine has shown promising benefits in relieving symptoms, promoting neurological recovery, and improving the quality of life of patients with IS. In TCM, Qi-deficiency along with blood-stasis (QDBS) syndrome is one of the common types of IS that is treated by invigorating Qi and activating blood circulation. In TCM theory, improving the corresponding degree of prescription–syndrome correlation (PSC) is helpful to improve clinical efficacy. In this study, we intend to use similar prescriptions that invigorate Qi and activate blood circulation: Buyang Huanwu granules (BHG), Naoxintong capsules (NXTC), and Yangyin Tongnao granules (YTG). The goal is to evaluate their level of PSC inpatients with IS with QDBS syndrome and find relevant biomarkers to provide an objective basis for precise treatment of TCM and improve the clinical therapeutic effects. A multicenter, randomized, double-blinded, and placebo-controlled intervention trial will be conducted in IS patients with QDBS syndrome, followed by an add-on of Chinese patent medicine. A total of 160 subjects will be randomly assigned to the BHG, NXTC, YTG, and placebo groups in a 1:2:1:1 allocation ratio. All subjects will undergo 28 days of treatment and then followed for another 180 days. The primary outcome is the changes in the National Institutes of Health Stroke Scale score after 28 days of medication. The secondary outcomes include the modified Rankin scale score, activity of daily living scale score, and TCM symptom score. Data will be analyzed in accordance with a predefined statistical analysis plan. Ethical approval of this trial has been granted by the Research Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (ID: 2017-Y-004-02). Written informed consent of patients will be required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR1800015189), and the results will be disseminated to the public through peer-reviewed journals and academic conferences.