Design and baseline characteristics of a population-based birth cohort in Shanghai / 上海预防医学

ObjectiveTo introduce the basic design， development plan and objectives of a population-based birth cohort in Shanghai， and further present the main data and baseline characteristics of enrolled participants in the cohort， and to provide key information for reproductive health-related studies. MethodsThe Shanghai population-based birth cohort initiated on January 1， 2005， included newborns born in Shanghai every year and their parents， and collected information on reproductive health， reproductive treatment， birth characteristics， growth and development status， as well as the incidence， treatment and death of diseases by employing data linkage technology and investigations. This formed a birth cohort spanning the entire life cycle. ResultsAs of October 2022， a total of 2 978 538 newborns and their parents were included in the cohort. Among them， 2 905 135 （97.54%） were naturally conceived （NC）， and 73 403 （2.46%） were born through assisted reproductive technologies （ART）. The average age of parents was （32.56±4.12） years old for females and （34.62±5.34） years old for males in the ART group， which was higher than （28.02±4.71） years and （30.07±5.54） years for parents in the NC group. Among parents， females and males aged 30 and above accounted for 77.12% and 85.08%， respectively， which were higher than that of parents （35.28% for females and 49.66% for males） in the NC group. Furthermore， the percentage of parents with a college degree or above in the ART group was 73.23% for females and 73.66% for males， which were higher than those in the NC group （49.98% and 50.91%， respectively）. The multiple births rate in the ART group was 33.81%， which was higher than that in the NC group （1.88%）. The incidence of premature birth and low birth weight in the ART group were 24.47% and 19.08%， respectively， which was higher than that in the NC group （5.47% and 3.73%）. ConclusionThe comprehensive collection of reproductive health-related information in the birth cohort in Shanghai can provide essential resources to determine the influence of genetics， environment， reproductive treatment and other related factors on the health of offspring after birth.

Changes in brain gray matter volume in nasopharyngeal carcinoma patients after radiotherapy in long-term follow-up

Abstract Objectives The aim of this study was to examine the changes in gray matter in nasopharyngeal carcinoma patients with normal hearing (Group 1) and nasopharyngeal carcinoma patients with hearing loss (Group 2) after radiotherapy using voxel-based morphological analysis and to analyze the relationship with the radiation doses of the temporal lobe. Methods 21 patients in Group 1, 14 patients in Group 2, and 21 healthy volunteers were selected. All participants underwent an otologic examination and three-dimensional magnetization preparatory rapid acquisition gradient echo sequence scan. The correlation between the variation of whole brain gray matter volume and the doses of the temporal lobe was analyzed by Data Processing & Analysis for Brain Imaging software. Results Compared with the normal control group, the brain areas with reduced gray matter volume in nasopharyngeal carcinoma patients after radiotherapy were mainly in the left posterior cerebellar lobe (T = −8.797), left insular lobe (T = −7.96), and the right insular lobe (T = −6.632). Compared to Group 1, the brain areas of Group 2 patients with reduced gray matter volume were mainly in the left superior temporal gyrus (T = −2.366), left olfactory bulb (T = −2.52), left Rolandic operculum (T = −2.431), and right olfactory bulb (T = −3.100). Compared with Group 1, the brain areas of Group 2 patients with increased gray matter volume were mainly in the left calcarine sulcus (T = 3.425) and right calcarine sulcus (T = 3.169). There were no correlations between the changes of brain gray matter volume and the radiation doses of the temporal lobe in both Group 1 and Group 2. Conclusions The radiotherapy may cause the changes of brain areas associated with cognitive function in nasopharyngeal carcinoma in a long-term follow-up. At the same time, nasopharyngeal carcinoma patients with the radiation-induced hearing loss had abnormal gray matter volumes in the auditory center and other sensory centers. Our findings might provide new understanding into the pathogenesis of radiation-induced brain damage in normal-appearing brain tissue. Yet this exploratory study should be taken with caution.

Risk prediction of low birth weight infants in Shanghai / 上海预防医学

ObjectiveTo investigate the risk factors of fertility behaviors with preterm birth and low birth weight， and to develop a nomogram model to predict the occurrence of low birth weight. MethodsBirth registration information in Shanghai from 2010 to 2020 was collected， and ANOVA and Chi-square tests were used to compare the differences in reproductive behavior factors and newborn health status across time. The odds ratio （OR） value and 95%CI were calculated by a multi-classification logistic regression model to determine the association between reproductive behavior factors and preterm birth or low birth weight infants. A nomogram model was established based on logistic model and the area under the ROC curve was used to assess the effect of the model. ResultsThis analysis included 2 089 384 live newborns. The incidence of full-term low birth weight， preterm normal weight and preterm low birth weight in Shanghai was 0.94%， 2.48% and 2.01%， respectively. From 2010 to 2020， 40.00% women had a history of abortion， the proportion of women who gave birth at age ≥40 years old increased from 1.05% to 2.24%， the proportion of fathers aged ≥40 years increased from 4.79% to 7.48%， and the proportion of women with postgraduate or above increased from 4.81% to 11.74%. The incidence of preterm low birth weight in Shanghai showed an increasing trend over time. Logistic regression analysis showed that the risk of preterm low birth weight was lower in female than in male infants （OR=0.97， 95%CI： 0.95‒0.98）， and the risk of full-term low birth weight was higher than in male infants （OR=1.85， 95%CI： 1.80‒1.90）. The risk of preterm birth and low birth weight was lower for couples of childbearing age with higher education. The risk of preterm low birth weight in newborns tended to increase with maternal age at childbirth >30 years， paternal age ≥40 years， and the number of abortions >2 times. Mother <25 or >35 years， father aged 30‒34 years， and the number of abortions >3 times were the risk factors of full-term low birth weight infants. ConclusionCouples of childbearing age who choose to have children at too high or too low age may increase the risk of preterm birth or low birth weight， so it is necessary to strengthen population awareness and promote age-appropriate childbirth. Multiple abortions are also associated with preterm birth and low birth weight， and it is advisable to popularize the scientific knowledge of contraception and birth control to reduce unnecessary abortions. The nomogram in the study can visualize the risk of full-term and low birth weight infant at different levels of factors， which can assist couples preparing for pregnancy in making decisions about the timing of childbirth and understanding the level of risk.

Peptide-drug conjugates (PDCs): a novel trend of research and development on targeted therapy, hype or hope?

Peptide-drug conjugates (PDCs) are the next generation of targeted therapeutics drug after antibody-drug conjugates (ADCs), with the core benefits of enhanced cellular permeability and improved drug selectivity. Two drugs are now approved for market by US Food and Drug Administration (FDA), and in the last two years, the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer, coronavirus disease 2019 (COVID-19), metabolic diseases, and so on. The therapeutic benefits of PDCs are significant, but poor stability, low bioactivity, long research and development time, and slow clinical development process as therapeutic agents of PDC, how can we design PDCs more effectively and what is the future direction of PDCs? This review summarises the components and functions of PDCs for therapeutic, from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability, targeting, and stability of the various components of PDCs. This holds great promise for the future of PDCs, such as bicyclic peptide‒toxin coupling or supramolecular nanostructures for peptide-conjugated drugs. The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised. The way is shown for future PDC development.

A study on personalized nutritional intervention based on nutritional assessment in long-term continuous nursing for elderly postoperative colorectal cancer patients / 中华临床营养杂志

Object:To explore the role of personalized nutritional intervention based on nutritional assessment in long-term continuous nursing of elderly postoperative colorectal cancer patients.Methods:Elderly patients with colorectal cancer who received radical surgery in a tertiary hospital in Beijing were screened from January 2021 to January 2022 and a total of 100 patients at nutritional risk (defined as with a Nutritional Risk Screening 2002 [NRS 2002] score ≥ 3) were included in the study. Patients were stratified by age and then divided into control and intervention groups with 50 cases in each. The control group received regular health guidance and follow-up visits at postoperative outpatient clinics while the intervention group received personalized nutritional intervention based on nutritional assessment additionally. The intervention period was 12 months. Nutritional indicators including body mass index (BMI), upper arm circumference, grip strength and hemoglobin, as well as albumin and quality of life (QoL), are compared between the two groups.Results:Compared with the control group, the intervention group showed significantly better results of BMI [(18.46±0.53) vs (16.9±0.77)], upper arm circumference [(25.09±1.41)cm vs (23.49±1.45)cm], grip strength [(28.34±8.00)kg vs (23.97±7.19)kg], HGB [(135.10±9.27)g/L vs (106.40±8.73)g/L] and ALB [(41.62±3.41)g/L vs (28.62±2.38)g/L, all P < 0.01]. The intervention group also had significantly higher scores in physical [(20.96±2.03) vs (15.66±0.82)], emotional [(21.48±1.64) vs (15.76±1.00)], social [(23.44±1.67) vs (15.96±0.99)], and functional [(20.74±1.74) vs (5.46±0.97)] domains of QoL (all P<0.01). Conclusion:In elderly patients with colorectal cancer after radical resection, personalized nutritional intervention based on nutritional assessment can effectively control nutritional indicators, help reduce the incidence of malnutrition, improve postoperative quality of life, and inform the establishment of standardized process in nutrition management.

Research on an integrated community-based chronic disease management model driven by massive databases / 上海预防医学

China’s chronic disease management suffers from problems such as unclear institutional function， insufficient information technology application， and weak regulation support. On the basis of current chronic disease management condition in China， this paper proposes to apply the concept of “people-centered” integrated health management to community chronic disease management and discusses the content and procedure of establishing an integrated community-based chronic disease management model driven by massive databases. The model innovatively combines technology integration， data integration and service integration， and can accurately and efficiently realize the "people-centered" full-course health management of various chronic diseases. Shanghai has provided integrated community-based chronic disease management service for 1.98 million citizens through applying this model. The model warrants further effectiveness and economic evaluation. This study provides precious experience for the development of chronic disease prevention and treatment in China.

Effectiveness of quality of care for patients with type 2 diabetes in China: findings from the Shanghai Integration Model (SIM) / 医学前沿

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai, China. A total of 173 235 patients with type 2 diabetes in 2017 were included in the analysis. Profiles of risk factors and intermediate outcomes were determined. The patients had a mean age of 66.43 ± 8.12 (standard deviation (SD)) years and a mean diabetes duration of 7.95 ± 5.53 (SD) years. The percentage of patients who achieved the target level for HbA1c (< 7.0%) was 48.6%. Patients who achieved the target levels for blood pressure (BP) < 130/80 mmHg and low-density lipoprotein-cholesterol (LDL-c) < 2.6 mmol/L reached 17.5% and 34.0%, respectively. A total of 3.8% achieved all three target levels, and the value increased to 6.8% with an adaptation of the BP target level (< 140/90 mmHg) for those over 65 years. Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels: male, young age, short diabetes duration, low body mass index, macrovascular complications, no microvascular complications, prescribed with lipid-lowering medication, and no prescription of antihypertensive medication. In conclusion, nearly 50% and one-third of the patients with diabetes met the target levels for HbA1c and LDL-c, respectively, with a low percentage achieving the BP target level. The percentage of patients who achieved all three target levels needs significant improvement.

Specific antitumor activity and mechanism of protonic bis-phenanthroline / 药学学报

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwise. The incidence rate of HCC is high and is easy to metastasis and recurrence, which seriously affects human health. Traditional chemical drugs have some challenges such as toxicity, side effects, and multidrug resistance, thus it is urgent to find new drugs and effective targets. Here we synthesized a novel chemical, protonic bis-phenanthroline (H-BP), and the antitumor effect was investigated in the study. The results showed that H-BP could selectively inhibit the proliferation of tumor cells and cause HCC apoptosis. And also, in HCC tumor-bearing mice, H-BP could effectively prevent the growth of tumor mass, even completely eliminate the tumor at medium dose (5 mg·kg-1) and high dose (10 mg·kg-1), and meanwhile H-BP has no significant effect on the body weight of mice. The experimental protocol was approved by the Animal Ethics Committee of Southwest University, and the experimental operation was strictly carried out in accordance with the ethical principles of animal use and care. Mechanism studies showed that H-BP induced HCC apoptosis was related to down-regulation the expression of pleomorphic adenoma gene like-2 (PLAGL2), a oncogene transcription factor, resulting in the down-regulation of PLAGL2 downstream proteins hypoxia inducible factor and β-catenin. This study not only introduces the dimerization method to form novel compounds that will provide a new approach for drug design, but also suggests that PLAGL2 may be an effective target in tumor therapy.

Construction and strategies of disease prevention and control system in the new era in Shanghai / 上海预防医学

After the epidemic of novel Coronavirus Disease 2019(COVID-19), construction of disease prevention and control has become a top priority. As a pioneer in the recovery of global economy and society, Shanghai should play a fundamental role in building a comprehensive system of public health and advanced disease prevention and control in the new era. In this article, we systematically categorize the requirements for the construction of disease prevention and control system in the new era, identify the weakness and challenges during and after the epidemic, and then make suggestions. It is proposed that we should utilize the important window period of the"14th Five-Year Plan", with the"Healthy China"strategy and municipal"20 Tasks for Public Health Construction"as the starting point, to make substantial contribution to the functional orientation, investment of resources, capacity building, operational mechanism and team building, which may provide scientific evidence for the reform and development of disease prevention and control system.

Current financing in disease control and prevention institutions in China / 上海预防医学

Objective To analyze the current situation of financing in disease control and prevention constitutions in China, to identify existing problems, to explore potential reasons, and to make policy recommendations accordingly. Methods Financial related indicators, including revenue and expense of disease control and prevention institutions, were collected through questionnaire survey. Moreover, some disease control and prevention institutions were selected for on-site survey. Results The proportion of public health institutions in the Total Health Expenditure had fallen from 7.0% in 2014 to 5.6% in 2018. The proportion of financial compensation in the operation of disease control and prevention institutions was less than 50%. The gap between revenue and expenditure had not been covered completely after the cancellation of three categories of administrative charges. In addition, financing mechanism of public health service funds remained unclear. Conclusion We recommend the strategies, including optimizing financing structure, increasing investment in disease control and prevention, increasing the level of financial guarantee, improving the mechanism of public health service funds, and multi-channel financing.

Perspectives on the construction of modern disease prevention and control system in Shanghai / 上海预防医学

It is a major public health task to promote the construction of modern disease prevention and control system in the prevention and control of the novel coronavirus pneumonia epidemic. In this study, we identified the current situation and challenges in the construction of disease prevention and control system in Shanghai, including the infrastructures, disciplines, human resources, information system, operational mechanism, and legalization. It is proposed that we should promote the construction of modern disease prevention and control system in Shanghai, which is aimed to improve the capacity in the disease prevention and control services, response to the major epidemics and public health emergencies, and scientific research in public health, in accordance with municipal functional orientation large-scale metropolitan public health security requirements in Shanghai. Moreover, we should promote policy-making, including upgrading infrastructures, facilitating discipline construction and scientific research innovation, optimizing development environment for human resources, accelerating comprehensive information construction, improving systems and mechanisms, and strengthening legal governance.

Exploration of reform and development of public health system in new era / 上海预防医学

There are many risks for public health and safety such as new outbreaks, imported and unknown contagious diseases, although the incidence of communicable diseases has been controlled well in general.This represents many opportunities and challenges in the development of public health with Chinese socialist characteristics in new era."Healthy China" is part of the national strategic plan and an important ingredient of "Chinese Dreams" for the rehabilitation of Chinese Nation.The functions of Center for Disease Control and Prevention (CDC), as a very important part of public health system, should be clarified and defined again.CDC needs to be modernized under the contents and balanced in the following aspects:public welfare and professionalism, wartime or peacetime, hierarchy with provincial/municipal county tiers.The new technologies such as internet+, big data, artificial intelligence, precision medicine, health insurance should be applied and combined in innovative models, be developed in multiple directions, and be collaborated broadly.The aims are to develop a new and reasonable way to meet the new era requirement and the needs of developing public health law.Then public health will greatly contribute to the building of "Healthy China".

Mechanism of melanoma growth inhibition by exogenous mitochondria / 药学学报

Alterations of mitochondrial structure and function in tumor cells allow cell survival and proliferation under hypoxic and acidic microenvironment. The effect of normal mitochondria on tumor initiation and development remains unknown. In this study, mice were euthanized by rapid cervical dislocation for isolation of hepatic mitochondria, which were injected intravenously to melanoma-bearing mice. This animal experiment had been approved by Southwest University Experiment Animal Ethics Review Committee. The results showed that exogenous mitochondria can significantly inhibit the growth of melanoma. Mitochondria isolated from the liver of young mice had more potent anti-melanoma effect than those isolated from aging mice. The average volume of tumors decreased significantly from 1.35 cm3 to 0.34 cm3, and the average mass of tumors decreased significantly from 0.63 g to 0.22 g. This anti-tumor mechanism might be associated with induction of mitophagy and cell necrosis after the exogenous mitochondria entering the melanoma cells. As mitotherapy can clinically improve somatic cell survival for treatment of pediatric patients with myocardial ischemia, the observed anti-tumor effect of exogenous mitochondria provides a hope for selective tumor treatment.

Current status and future perspectives of daptomycin development / 药学学报

Due to the potent bactericidal activity and low incidence of drug resistance, the novel cyclic lipopeptide antibiotic - daptomycin has emerged as one of the first line antimicrobial agents in the treatment of serious infections caused by gram-positive resistant pathogens. This review summarizes the research advances of daptomycin in recent years, mainly including spectrum of antimicrobial activity, biosynthesis, mode of action, mechanism of drug resistance, structure-activity relationships, surotomycin and siderophore-daptomycin conjugate to kill multidrug resistant Acinetobacter baumannii. The findings summarized in this review highlight the directions of next-generation of daptomycin derivatives.

Application and prospect of mitotherapy in mitochondria-related diseases / 中国药理学通报

Mitochondria is an important organelle in mammalian cells with multiple functions,such as ener-gy production and cell homeostasis maintaining. It is known that hundreds of diseases are associated with mi-tochondrial defects. The studies show that the exoge-nous mitochondria can directly enter mammalian cells in vitro, and they also can quickly transform into ani-mal tissues by local or intravenous injection. Current-ly, it has raised a new therapeutic strategy for mito-chondrial diseases, called mitotherapy, which trans-plants exogenous functional mitochondria into mito-chondria-defective cells. The mitochondria in recipient cells play their own roles, including energy produc-tion,maintaining free radical balance,and cell viabili-ty recovery. Since there is no effective method for mito-chondria-related diseases up to now, the mitotherapy will provide a new approach for the prevention and treatment of these diseases.

Novel antifungal agents against cryptococcal infections / 药学学报

Cryptococcal meningitis, caused by fungus Cryptococcus neoformans, is responsible for over a million infections and 600 000 deaths annually. Largely due to the limited treatment options and the intrinsic drawbacks coupled with drug resistance to current therapies, it is urgent to discover novel antifungal agents against cryptococcosis. An ideal antifungal drug should at least satisfy the following criteria: fungicidal, fungus-specific, permeable for the host barriers such as cell membranes of phagocytes and the blood-CNS barrier. Both discovery of candidates with novel mode of action and repurposing existing molecules with potent anti-cryptococcal activity are effective ways in discovery of new anti-cryptococcal agents. Here, we summarized recent advances in the study of anti-fungal activities, mechanisms of action, and clinical developments of new anti-cryptococcal drugs.

An analysis on the influencing factors and relationship of serum 25 (OH) D levels between late-term pregnant women and newborns / 预防医学

Objective To explore the influencing factors and relationship of serum 25 (OH) D levels between late-term pregnant women and newborns. Methods A total of 600 pregnant women and 600 newborns were selected in Lishui Maternal and Children Health Institution during 2016 and information were collected by questionnaires. Serum 25 (OH) D levels in pregnant women's venous bloods and newborns' cord bloods were tested respectively before and after delivery. Results Serum 25 (OH) D levels in 600 pregnant women's venous bloods before delivery were (36.25 ±14.92) nmol/L and 75.16% (451 pregnant women) had lower serum 25 (OH) D levels. Serum 25 (OH) D levels in newborns' cord bloods after delivery were (29.59±16.13) nmol/L and 82.50% (495 newborns) had lower serum 25 (OH) D levels. The relationship of serum 25 (OH) D levels between pregnant women and newborns was significant (r=0.892, P<0.05) . Vitamin D supplementation during pregnancy in pregnant women (400 IU/d) 25 (OH) D level was higher than those of not (P<0.05) . Serum 25 (OH) D levels of pregnant women were influenced by seasons (P<0.05) as higher in summer and autumn and lower in spring and winter. Conclusion Serum 25 (OH) D levels of pregnant women and newborns in Lishui were lower and different among seasons. Serum 25 (OH) D levels of pregnant women could have influence on serum 25 (OH) D levels of newborns. It should be encouraged to increase vitamin D intakes and outdoor activities, especially in spring and winter.

Neutrophil/lymphocyte ratio in prediction of incidence of ischemic stroke in elderly persons with chronic kidney disease / 中国医师杂志

Objective To investigate the relationship of the neutrophil to lymphocyte ratio (NLR)with stroke in elderly persons with CDK.Methods Totally 220 subjects with stage 3-5 CKD were followed.Fatal and nonfatal cerebrovascular event (CVE) were recorded during this period.NLR at baseline was determined from complete blood count differential.We investigated if NLR could predict stroke.Resuits Median NLR was 2.13.NLR was equally associated with estimated glomerular flitrationrate (eGFR).Totally 116 strokes occurred during follow-up period.NLR could predict stroke independently.Increased NLR over 2.13 was related to a significantly decreased survival time (log-rank Chi-square =4.963,P =0.026).Multivariate Cox regression analysis showed that the risk factor of ischemic stroke in CKD patients was high NLR,hazard ratio (HR) 1.11 [95％ confidence interval (CI) 1.007 to 1.223,P =0.035].Conclusions NLR could independently predict stroke in elderly patients with moderate to severe CKD.

A data-driven method for syndrome type identification and classification in traditional Chinese medicine / 中西医结合学报

The efficacy of traditional Chinese medicine (TCM) treatments for Western medicine (WM) diseases relies heavily on the proper classification of patients into TCM syndrome types. The authors developed a data-driven method for solving the classification problem, where syndrome types were identified and quantified based on statistical patterns detected in unlabeled symptom survey data. The new method is a generalization of latent class analysis (LCA), which has been widely applied in WM research to solve a similar problem, i.e., to identify subtypes of a patient population in the absence of a gold standard. A well-known weakness of LCA is that it makes an unrealistically strong independence assumption. The authors relaxed the assumption by first detecting symptom co-occurrence patterns from survey data and used those statistical patterns instead of the symptoms as features for LCA. This new method consists of six steps: data collection, symptom co-occurrence pattern discovery, statistical pattern interpretation, syndrome identification, syndrome type identification and syndrome type classification. A software package called Lantern has been developed to support the application of the method. The method was illustrated using a data set on vascular mild cognitive impairment.

Identification and classification of traditional Chinese medicine syndrome types among senior patients with vascular mild cognitive impairment using latent tree analysis / 中西医结合学报

<p><b>OBJECTIVE</b>To treat patients with vascular mild cognitive impairment (VMCI) using traditional Chinese medicine (TCM), it is necessary to classify the patients into TCM syndrome types and to apply different treatments to different types. In this paper, we investigate how to properly carry out the classification for patients with VMCI aged 50 or above using a novel data-driven method known as latent tree analysis (LTA).</p><p><b>METHOD</b>A cross-sectional survey on VMCI was carried out in several regions in Northern China between February 2008 and February 2012 which resulted in a data set that involves 803 patients and 93 symptoms. LTA was performed on the data to reveal symptom co-occurrence patterns, and the patients were partitioned into clusters in multiple ways based on the patterns. The patient clusters were matched up with syndrome types, and population statistics of the clusters are used to quantify the syndrome types and to establish classification rules.</p><p><b>RESULTS</b>Eight syndrome types are identified: Qi deficiency, Qi stagnation, Blood deficiency, Blood stasis, Phlegm-dampness, Fire-heat, Yang deficiency, and Yin deficiency. The prevalence and symptom occurrence characteristics of each syndrome type are determined. Quantitative classification rules are established for determining whether a patient belongs to each of the syndrome types.</p><p><b>CONCLUSION</b>A solution for the TCM syndrome classification problem for patients with VMCI and aged 50 or above is established based on the LTA of unlabeled symptom survey data. The results can be used as a reference in clinic practice to improve the quality of syndrome differentiation and to reduce diagnosis variances across physicians. They can also be used for patient selection in research projects aimed at finding biomarkers for the syndrome types and in randomized control trials aimed at determining the efficacy of TCM treatments of VMCI.</p>