Establishment and validation of embryo high-quality prediction models based on the third-day 340 nm absorbance embryo culture / 中国组织工程研究

BACKGROUND:A large number of previous studies have confirmed that a high concentration of metabolites is significantly correlated with embryo quality and clinical outcome,and the theory of silencing embryo development indicates that normally developed embryos maintain a low level of material exchange with the outside world during in vitro culture,while embryos often show abnormal metabolic activity due to stress repair mechanism when DNA damage occurs. OBJECTIVE:To establish and verify an embryo quality prediction model based on the third-day 340 nm absorbance embryo cultures to provide the basis for a more objective and accurate embryo quality assessment. METHODS:269 patients at the Nanxishan Hospital of Guangxi Zhuang Autonomous Region for in vitro fertilization and embryo transplantation from November 2019 to December 2021 were retrospectively analyzed.Among them,on day 3,162 cases who had 873 optimal embryos and 214 high-quality blastocysts were included in the high-quality embryo group.On day 3,107 cases who had 859 non-optimal embryos and 214 non-high-quality blastocysts were included in the non-high-quality embryo group.Lambert-beer law was used to screen out the characteristic wavelength with distinguishing degree between superior and non-superior embryos,analyze its correlation and influence trend with high-quality embryos,and establish the clinical prediction model and validation of absorbance for high-quality and non-high-quality embryos at this wavelength. RESULTS AND CONCLUSION:(1)There was a significant difference in absorbance between high-quality and non-high-quality embryos at 340 nm on day 3(P<0.001),and a negative correlation was found with the formation of high-quality embryos on day 3(r=-0.486,P<0.001).The absorbance of high-quality and non-high-quality blastocyst at 340 nm was significantly different(P<0.05),and was negatively correlated with the formation of high-quality blastocyst(r=-0.642,P<0.001).(2)The optimal cut-off value of absorbance at 340 nm between high-quality and non-high-quality embryos on day 3 was 0.235.The area under the curve was 0.799.Sensitivity was 62.9%.Specificity was 78.0%.Accuracy was 70.5%.The optimum cutoff value of high-quality and non-high-quality blastocysts of absorbance at 340 nm was 0.175.The area under the curve was 0.871.Sensitivity was 74.3%.Specificity was 89.1%.Accuracy was 82.2%.(3)Restricted cubic spline curve analysis showed that when the absorbance of the culture medium at 340 nm was greater than 0.221,there was a significant positive trend on the formation of non-high-quality embryos at day 3,and when the absorbance of the culture medium at 340 nm was greater than 0.160,there was a significant positive trend on the formation of non-high-quality blastocysts.(4)The clinical decision curve and clinical influence curve showed that the absorbance of the culture medium at 340 nm had the maximum clinical net benefit for the prediction models of high-quality embryos and high-quality blastocysts on the third day when the valve probability was 0.18-0.95 and 0.16-1.00,respectively,and the ratio of loss to gain within the valve probability range was always less than 1.It is proven that the prediction model has good efficacy in clinical applications.The results of embryo transfer showed that the absorbance of embryo culture medium at 340 nm in non-pregnant patients was significantly higher than that in clinical pregnancy,biochemical pregnancy and early abortion patients(P<0.05).(5)The high-quality and non-high-quality embryo culture in 340 nm absorbance has a significant difference with correlation.The embryo quality prediction model has a certain clinical value and application effectiveness.The joint embryo morphology evaluation to a certain extent improves the objectivity and accuracy of embryo quality evaluation.

Construction and validation of a nomogram model to predict abnormal female factors in in vitro fertilization / 中国组织工程研究

BACKGROUND:Reducing the rate of abnormal fertilization is an effective approach to improving the efficacy of in vitro fertilization and reducing patients'financial strain.However,the current research on abnormal fertilization has focused on exploring the types of prokaryotic nuclei and their generation mechanisms,as well as analyzing embryos formed by abnormal fertilization,chromosomal ploidy and utilization value.There is a lack of clinical prediction models for abnormal fertilization based on retrospective studies. OBJECTIVE:To construct a nomogram model to predict abnormal female factors in in vitro fertilization. METHODS:A total of 5 075 patients undergoing treatment for conventional in vitro fertilization at Nanxishan Hospital of Guangxi Zhuang Autonomous Region from March 2017 to March 2022 were retrospectively analyzed.The male confounders were calibrated on a 1:1 propensity score with a match tolerance of 0.02,and 1 672 cases were successfully matched.According to the Vienna Consensus,patients with≥60%normal fertilization capacity were included in the normal fertilization group(n=836)and those with<60%normal fertilization capacity were included in the abnormal fertilization group(n=836).The model and validation groups were obtained by random sampling at a ratio of 7:3.Factors related to the occurrence of abnormal fertilization following conventional in vitro fertilization in the model group were screened using univariate analysis and the best matching factors were selected using the Least Absolute Shrinkage and Selection Operator(LASSO)and included in a multifactorial forward stepwise Logistic regression to identify their independent influencing factors and plot a nomogram.Finally,the prediction model was validated for discrimination,accuracy and clinical application efficacy using receiver operating characteristic curves,calibration curves,clinical decision curves and clinical impact curves. RESULTS AND CONCLUSION:The univariate analysis indicated the factors influencing the occurrence of abnormal fertilization were age,controlled ovarian hyperstimulation protocol,number of assisted pregnancies,years of infertility,infertility factors,anti-mullerian hormone,sinus follicle count,basal luteinizing hormone,luteinizing hormone concentration on the human chorionic gonadotropin day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).LASSO regression further identified the best matching factors,including age,microstimulation protocol,number of assisted pregnancies,years of infertility,anti-mullerian hormone,luteinizing hormone level on human chorionic gonadotropin injection day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).Multifactorial forward stepwise Logistic regression results showed that age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day were independent influencing factors for the occurrence of abnormal fertilization following conventional in vitro fertilization.The receiver operating characteristic curves showed an area under the curve of 0.761(0.746,0.777)for the model group and 0.767(0.733,0.801)for the validation group,indicating that the model has good discrimination.The mean absolute error of the calibration curve was 0.044,and the Hosmer-Lemeshow test indicated that there was no significant difference between the predicted probability of abnormal fertilization and the actual probability of abnormal fertilization(P>0.05),indicating the prediction model has good consistency and accuracy.The clinical decision curves and clinical impact curves showed that the model and validation groups had the maximum net clinical benefit at valve probability values of 0.00-0.52 and 0.00-0.48,respectively,and there was a good clinical application efficacy in this valve probability range.To conclude,the nomogram model has good discrimination and accuracy as well as clinical application efficacy for predicting the occurrence of abnormal fertilization in women undergoing conventional in vitro fertilization based on age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day.

Construction of nomogram and validation of clinical prediction model for high-quality blastocyst formation in patients with unexplained infertility / 中国组织工程研究

BACKGROUND:Unexplained infertility is associated with a higher abortion rate and lower fertilization rate,implantation rate,clinical pregnancy rate and cumulative live birth rate.It is urgent to establish a clinical prediction model related to infertility of unknown cause to solve the problems of clinical prognosis and individualized medical services,and finally achieve the purpose of increasing the cumulative live birth rate of patients with infertility of unknown cause. OBJECTIVE:To construct and verify the prediction model of high-quality blastocyst formation in patients with unexplained infertility during in vitro fertilization. METHODS:A total of 419 patients with unknown infertility who underwent in vitro fertilization in the Assisted Reproduction Department of Changzhou Maternal and Child Health Care Hospital from March 2017 to June 2022 were retrospectively analyzed,including 317 patients with high-quality blastocysts and 102 patients without high-quality blastocysts.A prediction model was established and used as the model group.The model group was sampled 1 000 times by the Bootstrap method as the validation group.Firstly,the univariate analysis was used to screen the influencing factors of high-quality blastocyst formation of unknown infertility,and the best matching factors were selected by the least absolute shrinkage and selection operator(LASSO)algorithm.Multiple factors were included in the progressive Logistic regression to find out the independent influencing factors and draw a column graph.Finally,the subject working curve,calibration curve,clinical decision curve and clinical impact curve were used to verify the differentiation and accuracy of the prediction model as well as the clinical application efficiency. RESULTS AND CONCLUSION:(1)Univariate analysis of the factors influencing the formation of high-quality blastocyst of unknown infertility were age,insemination method,antimullerian hormone level,basal follicle-stimulating hormone level,basal luteinizing hormone level,human chorionic gonadotropin injection day follicle-stimulating hormone level,human chorionic gonadotropin day estradiol level,progesterone level on human chorionic gonadotropin day,the number of high-quality cleavage embryo(day 3)and the number of blastocyst formation(P<0.05).(2)The best matching factors further screened by LASSO regression were age,insemination method,antimullerian hormone level,basal luteinizing hormone level,human chorionic gonadotropin injection day follicle-stimulating hormone level,human chorionic gonadotropin day estradiol level,the number of high-quality cleavage embryo(day 3)and the number of blastocyst formation(P<0.05).Multifactor stepwise Logistic regression results showed that independent influencing factors on the formation of high-quality blastocysts for unexplained infertility were age,insemination method,antimullerian hormone level,the number of high-quality cleavage embryo(day 3),and the number of blastocyst formation.(3)Receiver operating characteristic curve exhibited that the area under the curve was 0.880(0.834,0.926)in the model group and 0.889(0.859,0.918)in the validation group.It showed that the prediction model had good differentiation.The average absolute error of the calibration curve was 0.036,indicating that the model had good accuracy.The Hosmer-Lemeshow test showed that there was no statistical difference between the prediction probability of blastocyst formation and the actual probability of blastocyst formation(P>0.05).The clinical decision curve and clinical impact curve showed that the model group and the validation group had the maximum clinical net benefit when the threshold probability value was(0.16-0.96)and(0.08-0.93),respectively,and had better clinical application efficacy within the threshold probability range.These findings concluded that age,insemination method,antimullerian hormone,the number of high-quality cleavage embryos(day 3),and the number of blastocyst formation were independent factors influencing the formation of the fine blastocyst in patients with unexplained infertility.The clinical prediction model constructed by these factors has good clinical prediction value and clinical application efficiency and can provide a basis for clinical prognosis and intervention as well as the formulation of individual medical programs.

Construction and validation of pregnancy prediction model of artificial insemination by husband based on endometrial structure and uterine spiral artery blood flow parameters / 中国组织工程研究

BACKGROUND:The impact of the endometrium's structure and spiral artery blood flow parameters on the pregnancy rate of artificial insemination by husband remains unclear.This study identified the independent factors and constructed a prediction model with good clinical application efficacy after calibration of other confounding factors. OBJECTIVE:To construct and validate a clinical pregnancy prediction model for artificial insemination by husband based on endometrial structure and uterine spiral artery blood flow parameters. METHODS:A retrospective analysis was conducted on 1 299 patients who underwent artificial insemination by husband treatment at Changzhou Maternal and Child Health Hospital from January 2017 to January 2021.The non-pregnancy group consisted of 1 182 patients,while the pregnancy group included 117 patients.Out of these patients,93 cases were successfully matched between the pregnancy and non-pregnancy groups using a 1∶1 propensity score matching method.Single-factor and multi-factor analyses were used to screen the endometrial structure and uterine spiral artery blood flow parameters to determine their influence on artificial insemination by husband outcomes.The optimal cutoff value was established for each independent influencing factor through receiver operating curve analysis and their risk trend affecting artificial insemination by husband pregnancy outcomes was analyzed using a restricted cubic spline.The clinical efficacy of this combined forecast model was tested by using clinical decision curve and clinical influence curve methods. RESULTS AND CONCLUSION:(1)There was no statistical significance in non-endometrial factors between the pregnancy group and the non-pregnancy group,and the data had a good balance by propensity score matching(P>0.05).(2)Single-factor analysis identified several subendometrial parameters as significant influencing factors of artificial insemination by husband pregnancy outcomes,including vascularization index,flow index,vascular flow index,resistance index,pulsatility index,maximum systolic velocity/end-diastolic velocity,thickness of average junction zone and maximum junction zone from the basal endometrium to the outer myometrium inner layer(P<0.05).(3)Multivariate logistic regression analysis revealed that thickness of average junction zone,pulsatility index,and vascular flow index were independent influencing factors of pregnancy outcomes of artificial insemination by husband,vascular flow index>thickness of average junction zone>pulsatility index.(4)Receiver operating characteristic curve analysis indicated that the area under receiver operating characteristic curve of vascular flow index was 0.704(0.629,0.779),and the optimal cutoff value was 6.26;the area under receiver operating characteristic curve of thickness of average junction zone was 0.660(0.582,0.739),and the optimal cutoff value was 6.38;the area under receiver operating characteristic curve of pulsatility index was 0.642(0.563,0.721),and the optimal cutoff value was 1.18.(5)The restricted cubic spline analysis revealed that artificial insemination by husband pregnancy outcomes were significantly positively affected when the vascular flow index was>6.24 or the thickness of average junction zone was≤6.55 mm,while a negative risk was associated with pulsatility index>1.27.(6)The clinical decision curve and clinical influence curve analyses exhibited that the combined prediction model had the maximum clinical net benefit at the threshold probability value of 0.17-0.93,and the ratio of loss to benefit was consistently less than 1 in the threshold probability range,indicating that the model had good clinical efficacy.(7)It is concluded that after adjusting for other confounding factors outside of the endometrium using propensity score matching and multifactorial logistic regression,the thickness of average junction zone,pulsatility index and vascular flow index were independent factors that influenced pregnancy outcomes of artificial insemination by husband.Through determining their optimal cutoff values and assessing their risk trends,it was confirmed that the combined prediction model had good predictive value and clinical efficacy.

Effect of traditional Chinese medicine in attenuating chronic kidney disease and its complications by regulating gut microbiota-derived metabolite trimethylamine N-oxide: a review / 中国中药杂志

Trimethylamine N-oxide(TMAO), a metabolite of gut microbiota, is closely associated with chronic kidney disease(CKD). It can aggravate the kidney injury and promote the occurrence of complications of CKD mainly by inducing renal fibroblast activation, vascular endothelial inflammation, macrophage foaming, platelet hyperreactivity, and inhibition of reverse cholesterol transport. Thus it is of great significance for clinical treatment of CKD to regulate circulating TMAO and alleviate its induced body damage. Currently, therapeutic strategies for TMAO regulation include dietary structure adjustment, lifestyle intervention, intestinal microflora regulation, and inhibition of intestinal trimethylamine synthesis and liver trimethylamine oxidation. Chinese medicinal herbs have the clinical advantage of multi-component and multi-target effects, and application of traditional Chinese medicine(TCM) to synergistically regulating TMAO and improving CKD via multiple pathways has broad prospects. This study systematically reviewed the clinical relevance and mechanism of TMAO in aggravating CKD renal function deterioration and complication progression. In addition, the effect and mechanism of TCM in improving TMAO-induced kidney injury, cardiovascular disease, hyperlipidemia, thrombosis and osteoporosis were summarized. The results provided a theoretical basis for TCM in attenuating gut microbiota-derived metabolite TMAO and improving CKD, as well as a basis and direction for in-depth clinical development and mechanism research in the future.

Efficacy of surgical comprehensive therapy for 456 cases of hypopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To retrospectively analyse the efficacy of surgerical comprehensive treatment for hypopharyngeal cancer. Methods: Four hundred and fifty-six cases of hypopharyngeal squamous cell carcinoma treated from Jan 2014 to Dec 2019 were analyzed retrospectively, including 432 males and 24 females, aged 37-82 years old. There were 328 cases of pyriform sinus carcinoma, 88 cases of posterior pharyngeal wall carcinoma, and 40 cases of postcricoid carcinoma. According to American Joint Committe on Cancer(AJCC) 2018 criteria, 420 cases were of stage Ⅲ or Ⅳ; 325 cases were of T3 or T4 stage. Treatment methods included surgery alone in 84 cases, preoperative planned radiotherapy plus surgery in 49 cases, surgery plus adjuvant radiotherapy or concurrent chemoradiotherapy in 314 cases, and inductive chemotherapy plus surgery and adjuvant radiotherapy in 9 cases. The primary tumor resection methods included transoral laser surgery in 5 cases, partial laryngopharyngectomy in 74 cases, of them 48 cases (64.9%) presented with supracricoid hemilaryngopharyngectomy, total laryngectomy with patial pharyngectomy in 90 cases, total laryngopharyngectomy or with cervical esophagectomy in 226 cases, and total laryngopharyngectomy with total esophagectomy in 61 cases. Among 456 cases, 226 cases received reconstruction surgery with free jejunum transplantation, 61 cases with gastric pull-up, and 32 cases with pectoralis myocutaneous flaps. All patients underwent retropharyngeal lymph node dissection, and high-definition gastroscopy was performed during admission and follow-up. SPSS 24.0 software was used to analyze the data. Results: The 3-year and 5-year overall survival rates were respectively 59.8%, and 49.5%. The 3-year and 5-year disease specific survival rates were respectively 69.0% and 58.8%. Total metastasis rate of retropharyngeal lymph nodes was 12.7%. A total of 132 patients (28.9%) suffered from simultaneous and metachronous multiple primary carcinoma of the hypopharynx. Multivariate Logistic regression analysis showed that T3-4 disease, cervical lymph node metastasis, retropharyngeal lymph node metastasis and postoperative adjuvant radiotherapy were independent factors affecting the prognosis of patients (all P<0.05). As of April 30, 2022, a total of 221 patients died during follow-up, of 109 (49.3%) with distant metastases, which were the main cause of death. Conclusions: The efficacy of comprehensive treatment for hypopharyngeal cancer can be improved by accurate preoperative evaluation, improved surgical resection, active retropharyngeal lymph node dissection and full process intervention of the second primary cancer.

Problems and development strategy of quality-oriented education for the medical students of the colleges and universities / 中华医学教育探索杂志

This article introduces American development process of quality-oriented education in colleges and universities which symbolizes practical teaching theory, and analyzes the reason that it is hard for colleges and universities to develop medical talents with strong humanistic quality and innovative ability. This article points out that medical colleges and universities need to make systematic standard and plan for quality-oriented education of practical teaching. The role of teachers is converting from single disseminator of theory knowledge to the instructor, organizer and participant of study. Meanwhile, the information technology should be embedded in practical teaching, which has profound effects on quality-oriented education development of medical students.

Clinical observation on Yi Jin Jing(Sinew-transforming Qigong Exercises)in improving anxiety for asymptomatic patients with COVID-19 infection during quarantine / 针灸推拿医学（英文版）

Objective:To observe the effect of Yi Jin Jing(Sinew-transforming Qigong Exercises)intervention on anxiety in asymptomatic patients with Corona Virus Disease 2019(COVID-19)infection during quarantine.Methods:A total of 160 asymptomatic patients with COVID-19 infection were stratified by gender and divided into an observation group and a control group by the stratified randomization method,with 80 cases in each group.The control group was given basic nursing in the cabin,and the observation group was given additional Yi Jin Jing exercises once a day,20 min each time,and trained continuously until 1 d before leaving the cabin.The Hamilton anxiety scale(HAMA)score was compared between the two groups.Results:A total of 154 cases were included for data analysis in this study,including 74 cases in the observation group and 80 cases in the control group.After intervention,the HAMA scores in both groups increased(P<0.05),while the score in the observation group was lower than that in the control group(P<0.05).In the control group,the HAMA score of females after intervention was higher than that of males.The scores of mental anxiety and somatic anxiety in both groups were higher than those before intervention,while the score of mental anxiety in the observation group was significantly lower than that in the control(P<0.05).However,there was no statistical difference in the somatic score between the two groups(P>0.05).Conclusion:Patients with COVID-19 infection will get anxious during quarantine.Yi Jin Jing exercise can effectively reduce the aggravation of anxiety in asymptomatic patients with COVID-19 infection during concentrated quarantine.

Clinical analysis of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma / 中华肿瘤杂志

Objective: To analyze the incidence and the related risk factors of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma, evaluate the accuracy of preoperative enhanced CT in judging retropharyngeal lymph node metastasis, and investigate the impact of retropharyngeal lymph node metastasis on the prognosis. Methods: Retrospective analyses were made on 398 patients with hypopharyngeal squamous cell carcinoma who underwent surgery as the primary therapy and accepted retropharyngeal lymph node exploration and clearance during surgery in Shandong Provincial ENT Hospital from January 2014 to December 2019. Multivariate logistic regression analysis was used to clarify the related risk factors of retropharyngeal lymph node metastasis. Multivariate Cox regression analysis was used to investigate the impact of retropharyngeal lymph node metastasis on prognosis. The retropharyngeal lymph nodes of 218 cases with available preoperative enhanced CT images were evaluated by two experienced radiologists and compared with postoperative pathological results. Results: Retropharyngeal lymph node metastasis were confirmed in 54 of 398 (13.6%) cases according to postoperative pathology. The sensitivity and specificity of preoperative enhanced CT in the diagnosis of retropharyngeal lymph node metastasis were 34.6% and 91.1%, respectively, and the overall accuracy was 84.4%. Multivariate logistic regression analysis showed that the site of the primary lesion and pathological N stage were independent risk factors for retropharyngeal lymph node metastasis in hypopharyngeal squamous cell carcinoma. Patients with primary lesion located in the posterior wall of hypopharynx (OR=4.83, 95% CI: 1.27-18.40), N2 stage (OR=6.30, 95% CI: 2.25-17.67), and N3 stage (OR=26.89, 95% CI: 5.76-125.58) were prone to retropharyngeal lymph node metastasis. The 5-year overall survival rate of the 398 patients was 50.4%, and the 5-year disease-free survival rate was 48.3%. Multivariate Cox regression analysis showed that T stage, N stage, retropharyngeal lymph node metastasis, and radiotherapy were independent influencing factors for overall survival (T stage: HR=1.28, 95% CI: 1.06-1.54; N stage: HR=1.26, 95% CI: 1.14-1.40; retropharyngeal lymph node metastasis: HR=2.13, 95% CI: 1.47-3.08; radiotherapy: HR=0.54, 95% CI: 0.38-0.76) and disease-free survival of patients with hypopharyngeal squamous cell carcinoma (T stage: HR=1.26, 95% CI: 1.06-1.51; N stage: HR=1.25, 95% CI: 1.13-1.37; retropharyngeal lymph node metastasis: HR=2.24, 95% CI: 1.56-3.21; radiotherapy: HR=0.55, 95% CI: 0.40-0.77). Conclusions: Metastasis of retropharyngeal lymph nodes in hypopharyngeal squamous cell carcinoma is not rare. Enhanced CT is of low accuracy and limited value in diagnosing retropharyngeal lymph node metastasis. Primary lesions located in the posterior wall of the hypopharyngx, N2 stage, and N3 stage are independent high-risk factors for retropharyngeal lymph node metastasis. The prognosis of hypopharyngeal cancer patients with retropharyngeal lymph node metastasis is worse, and active surgical exploration and clearance can effectively reduce the mortality caused by retropharyngeal lymph node metastasis.

Clinical analysis of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma / 中华肿瘤杂志

Objective: To analyze the incidence and the related risk factors of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma, evaluate the accuracy of preoperative enhanced CT in judging retropharyngeal lymph node metastasis, and investigate the impact of retropharyngeal lymph node metastasis on the prognosis. Methods: Retrospective analyses were made on 398 patients with hypopharyngeal squamous cell carcinoma who underwent surgery as the primary therapy and accepted retropharyngeal lymph node exploration and clearance during surgery in Shandong Provincial ENT Hospital from January 2014 to December 2019. Multivariate logistic regression analysis was used to clarify the related risk factors of retropharyngeal lymph node metastasis. Multivariate Cox regression analysis was used to investigate the impact of retropharyngeal lymph node metastasis on prognosis. The retropharyngeal lymph nodes of 218 cases with available preoperative enhanced CT images were evaluated by two experienced radiologists and compared with postoperative pathological results. Results: Retropharyngeal lymph node metastasis were confirmed in 54 of 398 (13.6%) cases according to postoperative pathology. The sensitivity and specificity of preoperative enhanced CT in the diagnosis of retropharyngeal lymph node metastasis were 34.6% and 91.1%, respectively, and the overall accuracy was 84.4%. Multivariate logistic regression analysis showed that the site of the primary lesion and pathological N stage were independent risk factors for retropharyngeal lymph node metastasis in hypopharyngeal squamous cell carcinoma. Patients with primary lesion located in the posterior wall of hypopharynx (OR=4.83, 95% CI: 1.27-18.40), N2 stage (OR=6.30, 95% CI: 2.25-17.67), and N3 stage (OR=26.89, 95% CI: 5.76-125.58) were prone to retropharyngeal lymph node metastasis. The 5-year overall survival rate of the 398 patients was 50.4%, and the 5-year disease-free survival rate was 48.3%. Multivariate Cox regression analysis showed that T stage, N stage, retropharyngeal lymph node metastasis, and radiotherapy were independent influencing factors for overall survival (T stage: HR=1.28, 95% CI: 1.06-1.54; N stage: HR=1.26, 95% CI: 1.14-1.40; retropharyngeal lymph node metastasis: HR=2.13, 95% CI: 1.47-3.08; radiotherapy: HR=0.54, 95% CI: 0.38-0.76) and disease-free survival of patients with hypopharyngeal squamous cell carcinoma (T stage: HR=1.26, 95% CI: 1.06-1.51; N stage: HR=1.25, 95% CI: 1.13-1.37; retropharyngeal lymph node metastasis: HR=2.24, 95% CI: 1.56-3.21; radiotherapy: HR=0.55, 95% CI: 0.40-0.77). Conclusions: Metastasis of retropharyngeal lymph nodes in hypopharyngeal squamous cell carcinoma is not rare. Enhanced CT is of low accuracy and limited value in diagnosing retropharyngeal lymph node metastasis. Primary lesions located in the posterior wall of the hypopharyngx, N2 stage, and N3 stage are independent high-risk factors for retropharyngeal lymph node metastasis. The prognosis of hypopharyngeal cancer patients with retropharyngeal lymph node metastasis is worse, and active surgical exploration and clearance can effectively reduce the mortality caused by retropharyngeal lymph node metastasis.

Research progress of iron metabolism and its mechanism in the treatment of heart failure / 药学学报

The pathogenesis of heart failure is a complex progression and associated with abnormal regulation of many signaling pathways. As a cofactor of hemoglobin, myoglobin, oxidative respiratory chain, DNA synthase and other important proteins, iron plays an indispensable role in myocardial energy metabolism. Recently, a large number of studies have shown that heart failure is related to the disorder of iron metabolism. Both iron deficiency and iron overload can lead to the development of a variety of cardiomyopathy, and even progress to heart failure. Iron metabolism could be a key target for the diagnosis, prevention and treatment of heart failure. Here, we review the basic process of iron metabolism and its mechanism in heart failure, expecting to provide new clues and evidence for the treatment of heart failure.

Severe cervical kyphosis treated by anterior and posterior approach: case report and literature review / 中华骨科杂志

For the moment, the surgical treatment of severe rigid cervical kyphosis is still one of the difficulties in the treatment of spinal deformity. There were not consistent in the stage of correction, choice of osteotomy method, osteotomy scope and approach. In this paper, It was expected to get further understanding by sharing one case of severe cervical kyphosis treated by anterior and posterior approach, and reviewing literature. The patient was a 23-year-old female who had functional limitation due to cervical deformity for 3 years. It showed that the cervical kyphosis vertex was C 3, 4 segment, the Cobb angle was 86°, the flexibility was 8.1%, and the atlantoaxial vertebra was dislocated and unstable by the examination of X-ray, MRI, CT and CTA examination. The cervical segmental, sequence, morphological characteristics of pedicle and lateral mass, and running of the vertebral artery were also evaluated. The deformity was corrected by a one-stage operation combined anterior and posterior approaches for intervertebral and atlantoaxial release, osteotomy of the posterior lamina articular process and fusion with bone grafting. The cervical lordosis angle was recovered to 6.7°. The patients were followed up for 4 years. There were no operative and perioperative complications and we obtained satisfied surgical result.

Effects of Interactive Dynamic Scalp Acupuncture on Motor Function and Gait of Lower Limbs after Stroke: A Multicenter, Randomized, Controlled Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the effects of interactive dynamic scalp acupuncture (IDSA), simple combination therapy (SCT), and traditional scalp acupuncture (TSA) on motor function and gait of the lower limbs in post-stroke hemiplegia patients.@*METHODS@#A total of 231 patients with post-stroke hemiplegia was randomly divided into IDSA (78 cases), SCT (78 cases), and TSA (75 cases) groups by a random number table. Scalp acupuncture (SA) and lower-limb robot training (LLRT) were both performed in the IDSA and SCT groups. The patients in the TSA group underwent SA and did not receive LLRT. The treatment was administered once daily and 6 times weekly for 8 continuous weeks, each session lasted for 30 min. The primary outcome measures included Fugl-Meyer assessment of the lower extremity (FMA-LE), berg balance scale (BBS), modified barthel index (MBI), and 6-min walking test (6MWT). The secondary outcome measures included stride frequency (SF), stride length (SL), stride width (SW), affected side foot angle (ASFA), passive range of motion (PROM) of the affected hip (PROM-H), knee (PROM-K) and ankle (PROM-A) joints. The patients were evaluated before treatment, at 1- and 2-month treatment, and 1-, and 2-month follow-up visits, respectively. Adverse events during 2-month treatment were observed.@*RESULTS@#Nineteen patients withdrew from the trial, with 8 in the IDSA and 5 in the SCT groups, 6 in the TSA group. The FMA-LE, BBS, 6MWT and MBI scores in the IDSA group were significantly increased after 8-week treatment and 2 follow-up visits compared with the SCT and TSA groups (P<0.05 or P<0.01). Compared with pre-treatment, the grade distribution of BBS and MBI scores in the 3 groups were significantly improved at 1, 2-month treatment and 2 follow-up visits (P<0.05 or P<0.01). The SF, PROM-H, PROM-K and PROM-A in the IDSA group was significantly increased compared with the SCT and TSA groups after 8-week of treatment (P<0.05 or P<0.01). Compared with the SCT group, ASFA of the IDSA group was significantly reduced after 8-week of treatment (P<0.05). SF, SL, PROM-K and PROM-A were significantly increased at the 2nd follow-up visit whereas the ASFA was significantly reduced in the IDSA group compared with the SCT groups at 1st follow-up visit (P<0.05 or P<0.01). The SF was significantly increased in the SCT group compared with the TSA group after 8-week treatment (P<0.05). Compared with the TSA group, PROM-K, PROM-A were significantly increased at the 2nd follow-up visit (P<0.05).@*CONCLUSIONS@#The effects of IDSA on lower-limb motor function and walking ability of post-stroke patients were superior to SCT and TSA. The SCT was comparable to TSA treatment, and appeared to be superior in improving the motion range of the lower extremities. (Registration No. ChiCTR1900027206).

Effect of Interactive Dynamic Scalp Acupuncture on Post-Stroke Cognitive Function, Depression, and Anxiety: A Multicenter, Randomized, Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To compare the clinical effects of interactive dynamic scalp acupuncture (IDSA), simple combination therapy (SCT), and traditional scalp acupuncture (TSA) on cognitive function, depression and anxiety in patients with post-stroke cognitive impairment.@*METHODS@#A total of 660 patients with post-stroke cognitive impairment who were admitted to 3 hospitals in Shenzhen City between May 2017 and May 2020 were recruited and randomly assigned to the IDSA (218 cases), SCT (222 cases) and TSA groups (220 cases) according to a random number table. All the patients received conventional drug therapy for cerebral stroke and exercise rehabilitation training. Scalp acupuncture and computer-based cognitive training (CBCT) were performed simultaneously in the IDSA group, but separately in the morning and in the afternoon in the SCT group. The patients in the TSA group underwent scalp acupuncture only. The course of treatment was 8 weeks. Before treatment (M0), 1 (M1) and 2 months (M2) after treatment, as well as follow-up at 1 (M3) and 2 months (M4), the cognitive function of patients was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA) Scales; depression, anxiety, sleep quality, and self-care ability of patients were assessed using Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Pittsburgh Sleep Quality Index (PSQI), and Modified Barthel Index (MBI), respectively. During this trial, all adverse events (AEs) were accurately recorded.@*RESULTS@#There were no significant differences in the MMSE, MoCA, HAMD, HAMA, PSQI, and MBI scores among the 3 groups at M0 (all P>0.05). In the IDSA group, the MMSE, MoCA and MBI scores from M2 to M4 were significantly higher than those in the SCT and TSA groups, while the HAMD, HAMA and PSQI scores were significantly reduced (all P<0.01). The changes of all above scores (M2-M0, M4-M0) were significantly superior to those in the SCT and TSA groups (all P<0.01, except M4-M0 of HAMD). At M2, the severity of MMSE, HAMD, HAMA, PSQI and MBI in the IDSA group was significantly lower than that in the SCT and TSA groups (all P<0.01). There was no serious AE during this trial.@*CONCLUSIONS@#IDSA can not only significantly improve cognitive function, but also reduce depression, anxiety, which finally improves the patient's self-care ability. The effect of IDSA was significantly better than SCT and TSA. (Trial registration No. ChiCTR1900027206).

Etiological detection and epidemiological analysis of children with influenza-like illness / 中华检验医学杂志

Objective:To analyze the status and epidemiological characteristics of respiratory virus infection in children with influenza-like illness in outpatient department, and to provide evidence for the prevention and treatment of children in this area.Methods:Nasopharyngeal swab samples were collected from children who attended the fever clinic of The Children′s Hospital, Zhejiang University School of Medicine due to influenza-like illness from July 2021 to March 2022, and six common respiratory virus nucleic acids were detected by reverse transcription-polymerase chain reaction (RT-PCR). The general information of the children was collected and grouped by gender and age (0-<6 months, 6-<12 months, 1-3< year-old, 3-<6 year-old , and ≥6 year-old), and the chi-square test was used for statistical analysis between the groups to explore the epidemic pattern of respiratory viruses.Results:A total of 739 cases (45.9%, 739/1 609) of respiratory viruses were detected from children with influenza-like illness, including 651 cases (40.5%, 651/1 609) of simple infection and 88 cases (5.5%, 88/1 609) of multiple infections. Respiratory syncytial virus (RSV) was detected in 18.6% (300/1 609), followed by influenza B virus (FluB) in 11.9% (192/1 609), adenovirus (ADV) in 8.3% (134/1 609), parainfluenza virus type 3 (PIV-3) in 7.6% (123/1 609), parainfluenza virus type 1 (PIV-1) in 4.9% (79/1 609), and influenza A virus (FluA) in 0.4% (6/1 609). Multiple infections including double or triple infections, with 81(92.0%, 81/88) cases of double infection and the most common being ADV+RSV (22.7%, 20/88) and 7 (8.0%, 7/88) cases of triple infection. There was a significant difference in the virus detection rate between the age groups (χ2=17.078, P=0.002), with the highest virus detection rate in the 3-<6 years of age group (49.7%, 286/575). Among the detection of simple infection, FluB had the highest detection rate in the ≥ 6 years of age group (26.6%, 98/369), and RSV and PIV-1 had the highest detection rate in the 3-<6 years of age group (20.0%, 115/575 and 5.9%, 34/575). The total monthly virus detection rate increased from 26.8% (37/138) in July to 63.0% (58/92) in January, and decreased to 46.1% (106/230) and 26.8% (37/138) in February and March. The detection rate of RSV was the highest from August to November, the detection rate of FluB was the highest from December to March, the detection rate of ADV increased in December and January, and the detection rate of PIV-3 increased from October to December; the detection rate of PIV-1 did not fluctuate significantly, and FluA was sporadically detected. Conclusions:RSV is the main respiratory virus in children with influenza-like illness. Most respiratory viruses are present as single infections. Multiple infections are more common in double infections. FluB, RSV and PIV-1 infections showed certain age distribution characteristics, especially in children over 3 years of age. The epidemic characteristics of respiratory virus infection show that the epidemic gradually peaks from summer to autumn and winter, and turns into an epidemic decline in spring. RSV was relatively prevalent in autumn, FluB was prevalent in winter and spring, ADV and PIV-3 were prevalent to varying degrees in winter, PIV-1 continued to circulate at a low level, and FluA did not present epidemic characteristics.

Therapeutic efficacy observation of Tuina manipulation for pediatric adenoid hypertrophy / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of Tuina (Chinese therapeutic massage) manipulation for pediatric adenoid hypertrophy (AH). Methods: A total of 60 children with AH were randomized into an observation group and a medication group, with 30 cases in each group. The observation group was treated with pediatric Tuina treatment, and the medication group was treated with 0.05％ mometasone furoate nasal spray. The changes of main clinical symptom score, quality of life (QOL) score and X-ray nasopharynx lateral film were observed, and the clinical efficacy was evaluated. Results: The total effective rate of the observation group was 90.0％, and that of the medication group was 66.7％. The difference between the two groups was statistically significant (P<0.05). After treatment, the A/N value [ratio of adenoid thickness (A) and nasopharyngeal cavity width (N)] of posterior nasopharyngeal lateral film did not show significant change in either group (P>0.05). After treatment, the clinical symptom scores in both groups decreased, and the intra-group differences were statistically significant (P<0.001), but there was no statistical difference between the two groups (P>0.05). After treatment, the QOL scores of children in both groups decreased, and the intra-group differences were statistically significant (P<0.001), and the difference between the two groups was statistically significant (P<0.001). Conclusion: Tuina manipulation is effective in treating pediatric AH, and produces a better effect in improving traditional Chinese medicine symptoms and QOL than 0.05％ mometasone furoate nasal spray.

Denture applicators with 125I seeds for treatment of palatal malignant tumors / 中国医师杂志

Objective:To explore the clinical application and curative effect of brachytherapy of denture applicators with 125I seeds in the treatment of palatal malignant tumor. Methods:Thirty patients with palatal malignant tumor who underwent surgical resection in Shandong Provincial Hospital from February 2012 to January 2020, and brachytherapy was performed with applicator additional 125I seeds 2 weeks after surgery. All patients were followed up for treatment effect and adverse reactions. Results:All patients wore 125I seeds denture base denture applicator well, no 125I seeds displacement and loss. 30 patients had 10-60 months of follow-up, among which 1 patient received palliative treatment with 125I seeds denture applicator alone died after 10 months of follow-up; 1 patient with adenoid cystic carcinoma recurred after 2 years of follow-up and underwent surgical treatment again; the rest patients did not see tumor recurrence or metastasis. The side effects, pronunciation and chewing function were improved in patients ( P<0.05). Conclusions:For patients with palatal malignant tumor, postoperative 125I seeds denture applicator can effectively prevent tumor recurrence and metastasis, reduce complications, and improve the quality of life.

Systematic Review and Meta-Analysis of Antibiotic-Impregnated Shunt Catheters on Anti-Infective Effect of Hydrocephalus Shunt

Objective@#: Shunt infection is a common complication while treating hydrocephalus. The antibiotic-impregnated shunt catheter (AISC) was designed to reduce shunt infection rate. A meta-analysis was conducted to study the effectiveness of AISCs in reduction of shunt infection in terms of age, follow-up time and high-risk patient population. @*Methods@#: This study reviewed literature from three databases including PubMed, EMBASE, and Cochrane Library (from 2000 to March 2019). Clinical studies from controlled trials for shunt operation were included in this analysis. A subgroup analysis was performed based on the patient’s age, follow-up time and high-risk population. The fixed effect in RevMan 5.3 software (Cochrane Collaboration) was used for this meta-analysis. @*Results@#: This study included 19 controlled clinical trials including 10105 operations. The analysis demonstrated that AISC could reduce the infection rate in shunt surgery compared to standard shunt catheter (non-AISC) from 8.13% to 4.09% (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.40–0.58; p=0.01; I2=46%). Subgroup analysis of different age groups showed that AISC had significant antimicrobial effects in all three groups (adult, infant, and adolescent). Follow-up time analysis showed that AISC was effective in preventing early shunt infections (within 6 months after implant). AISC is more effective in high-risk population (OR, 0.24; 95% CI, 0.14–0.40; p=0.60; I2=0%) than in general patient population. @*Conclusion@#: The results of meta-analysis indicated that AISC is an effective method for reducing shunt infection. We recommend that AISC should be considered for use in infants and high-risk groups. For adult patients, the choice for AISC could be determined based on the treatment cost.

Case Analysis and Literature Review of a Case of Acarbose-induced Skin ADR by Clinical Pharmacists / 中国药房

OBJECTIVE：To summarize and analyze t he clinical characteristics of acarbose-induced skin ADR ，and to provide reference for its therapy. METHODS ：Clinical pharmacists participated in the treatment of a patient with acarbose-induced skin ADR. The patient developed erythema multiforme several days after oral administration of Acarbose tablets （100 mg/d）. After consultation by dermatology and clinical pharmacy ，considering that the adverse reaction was related to acarbose ，clinical pharmacists suggested to stop the drug. Based on the above cases ，clinical pharmacists searched Wanfang database ，CNKI， PubMed，Embase and other databases to collect case reports of skin ADR caused by acarbose ，summarize its general situation （gender，age，usage and dosage ，etc.），latency，ADR（diagnosis and manifestation ），intervention and outcome ，etc. RESULTS ： The doctor adopted the pharmacist s’advice，stopped the use of acarbose ，and gave symptomatic treatment as Methylprednisolone sodium succinate for injection 40 mg（intravenous injection ，qd）+Medloratadine tablets 8.8 mg（oral administration ，qd）+Calamine lotion（for external use ）. The patient improved and was discharged after 10 days. A total of 12 literatures involving 12 patients were retrieved. Among the 13 patients included in the analysis （including the above clinical case and 12 literature cases ），there were 8 males and 5 females，and 8 patients of them aged 50 and over；the dosage of acarb ose in most patients was within the requirements of the drug instructions. The primary diseases of 12 patients were diabetes mellitus. The latency of skin ADR in 11 patients was within 6 days of administration. Among the 13 patients，the ADR were diagnosed as rash in 4 cases，pustulosis in 3 cases， erythema multiforme in 2 cases， urticaria in 2 cases， maculopapular rash in 1 case and lip swelling in 1 case. The ADR of 1 patient improved after drug withdrawal ，and 12 patients also improved after drug withdrawal and symptomatic treatment such as glucocorticoid or antihistamine. Acarbose was re-used in 2 patients after the improvement of first skin ADR ，and skin ADR occurred again ，and the ADR were improved after drug withdrawal and symptomatic treatment. CONCLUSIONS ：Skin ADR are acarbose-induced rare ADR ，mostly within 6 days of medication ，and are more likely to occur in middle-aged and older men. When the patients suffer from ADR ，the drug should be stopped in time and given glucocorticoids or antihistamines for symptomatic treatment. Clinical pharmacists should do a good job in drug publicity and education ，remind patients to closely monitor relevant indicators and ensure drug safety.

Effects of physical activities on cognitive flexibility of Chinese children and adolescents: a Meta analysis / 中国学校卫生

Objective@#The purpose of this paper is to systematically review the impact of physical activities on cognitive flexibility of children and adolescents in China, and to provide evidence based evidence for relevant research on improving cognitive flexibility of children and adolescents by using physical activities.@*Methods@#CNKI, VIP, Wanfang Data, Web of Science, SPORTDiscus, PubMed, Springer link and Science Direct database were searched. The time span of 40 articles collected in this study was from the establishment of the database to December 31, 2020.@*Results@#A total of 3 262 research samples were included in 40 articles, including 1 674 in the experimental group and 1 588 in the control group. Meta analysis showed that the total effect WMD value of literature was 121.11, Z =12.37, 95% CI =101.91-140.30 ( P <0.01); the sub group of school age children included 32 literatures, and the combined effect WMD value was 126.05, Z =10.42, 95% CI =102.34-149.76 ( P <0.01); the sub group of adolescents included 8 literatures, the combined effect WMD value was 104.00, Z =9.72, 95% CI =83.02-124.98 ( P <0.01). Compared with the control group, physical activity had a significant positive effect on the cognitive flexibility of Chinese children and adolescents. The source of heterogeneity in school age children group was tested by meta regression method. The results showed that the type of children t =12.77, 95% CI =28.79-39.74( P <0.01) was the primary source of heterogeneity in Meta analysis. The results of egger regression analysis showed that t =0.47, 95% CI =-1.48-2.37( P =0.64), and there was no publication bias.@*Conclusion@#Adolescence is the sensitive period for development of cognitive flexibility, and physical activities have a significant positive impact on the cognitive flexibility of children and adolescents.