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Objective To explore the construction idea and application method of knowledge base and knowledge mining system for the prevention and treatment of diseases in traditional Chinese medicine.Methods Guided by the theory of traditional Chinese medicine(TCM),firstly,the knowledge system of TCM Prevention and treatment was sorted out,and the structure and relationship of TCM Prevention and treatment knowledge base were designed according to the classification method of TCM Prevention and treatment;Secondly,according to the needs of pre treatment research,the ancient and modern literature data sources and knowledge collection methods of TCM pre treatment database are proposed;Then,under the framework of the pre treatment classification system,the core knowledge is studied in the aspects of professional annotation,relationship extraction,knowledge audit,and a variety of data mining algorithms are introduced to analyze and mine the knowledge;Finally,the massive data obtained are combined with big data analysis and computer machine learning to realize intelligent information collection,disease analysis and diagnosis and treatment suggestions.Results Under the guidance of traditional Chinese medicine theory,the knowledge base of traditional Chinese medicine for prevention and treatment of diseases can digitize,digitize and intellectualize the basic knowledge and clinical knowledge of traditional Chinese medicine for prevention and treatment of diseases,and can objectively mine and analyze the data,providing a basis for the service and sharing of knowledge of traditional Chinese medicine for prevention and treatment of diseases.Conclusion The knowledge base of TCM Prevention and treatment is an important way for the digital storage of TCM Prevention and treatment knowledge,and provides literature knowledge support and objective evidence of data mining for TCM Prevention and treatment research.
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Platinum-based nanoplatforms can enhance the absorption of X-ray due to the presence of high atomic number element of platinum and are applied to computed tomography imaging.Meanwhile,platinum-based nanomaterials have good near-infrared light absorption properties and photothermal conversion efficiency,which make them capable of photothermal imaging and photoacoustic imaging.In addition,by reducing transverse and longitudinal relaxation time,platinum-based nanoplatforms can mediate MRI imaging.In this paper,we report a multimodal imaging system based on platinum-based nanoplatforms for guiding the development of cancer treatment and diagnosis platform and medical application research,and also summarize the prospects of multimodal imaging technology in cancer diagnosis and treatment,report the research progress of platinum-based nanoplatforms in improving the contrast of medical images and enhancing cancer treatment.
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Objective To analyze the TCM syndrome and treatment rule for the treatment of chronic atrophic gastritis based on data mining;To provide reference for its clinical treatment.Methods With the help of the big data platform of evidence-based literature of TCM covering several dominant diseases in the field of digestion,literature on the experience of famous doctors,theoretical discussion and case reports in the treatment of chronic atrophic gastritis published from 1 January 2000 to 31 July 2022 was retrieved.Medical records were screened according to the inclusion and exclusion criteria.The data of TCM disease names,clinical symptoms,tongue manifestation,pulse manifestation,TCM syndrome,TCM treatment method and other terms in medical records were standardized and statistically analyzed.Results Totally 169 articles were included,including 228 medical cases,involving 228 patients,with a cumulative number of 361 visits,with an average age of(53.17±11.11)years old,with the largest number of 50-60 years old.Chronic atrophic gastritis mostly belonged to the categories of"stomach pain"and"epigastric puffiness"in TCM,and its main symptoms were stomach pain,epigastric puffiness and belching.The common tongue manifestation include dark red tongue,white moss,thin or greasy moss.The common pulse manifestation included wiry slippery pulse,wiry thready pulse and wiry pulse.The high-frequency syndromes included liver-stomach qi stagnation syndrome,spleen-stomach dampness-heat syndrome,liver-qi stagnation and spleen-qi deficiency syndrome.The disease locations were mainly in the stomach,spleen and liver,and the syndrome elements were mainly qi deficiency,qi stagnation,blood stasis,dampness and heat,etc.The complex syndrome elements were more than the single syndrome elements,and the two syndrome elements of qi deficiency + qi stagnation was the most common.The most commonly used treatment methods were supplementing,regulating qi and regulating blood.Conclusion The treatment of chronic atrophic gastritis with TCM mostly focuses on the stomach,spleen and liver.The core syndrome elements are qi deficiency,qi stagnation,and blood stasis.The methods of nourishing qi and strengthening the spleen,soothing the liver and stomach,regulating qi and blood are often used.
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Medical cases are an important mean to record the clinical treatment process for TCM doctors. With the help of big data processing technology and other means, digging and using of medical cases information is of great significance for the inheritance of TCM. TCM Cases Cloud integrates voice recognition, optical character recognition (OCR), four-diagnosis instrument of TCM and other intelligent information collection technologies, as well as abundant algorithms such as association analysis, Bayes, hierarchical clustering, etc. to dig the laws of syndrome differentiation, selection of prescriptions, medication, acupoint, etc. of famous TCM doctors in medical records. This article briefly introduced the platform from five aspects: the excavation of the experience of famous TCM doctors in modern times, the summary of the academic thoughts of ancient medical cases, the analysis of the law of diagnosis and treatment of specialized diseases, the regularity of a single drug and drug pairs, and the exploration of the compatibility of TCM prescriptions.
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Outpatient information management system is an important part of hospital information system,which plays an important role in hospital management,patient treatment,medical insurance reimbursement and settlement.This study integrated the application modes of big data,cloud computing,Internet of things and other cutting-edge technologies of artificial intelligence,focused on the intelligent decision support and whole-process simplified management of the diagnosis and treatment behavior of clinical TCM physicians,and developed a cloud intelligent TCM outpatient system for primary medical care.The system has intelligent medical functions such as intelligent prescription monitoring driven by the rule engine and intelligent recommendation of traditional Chinese medicine knowledge.It seamlessly connects with the intelligent four-diagnosis instrument for information collection and medical order input,and realizes the cloud storage,computing,distribution,management,service and outpatient process,multi-directional and convenient management mode.
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The meridian theory is the pioneer of clinical diagnosis and treatment of diseases in Traditional Chinese Medicine (TCM). From Shang Han Lun to Pi Wei Lun, the meridian theory has contributed important theoretical organization materials and clinical practice experience to the establishment of the diagnosis system of external and internal injuries. The acupoints contained in its clinical acupuncture and moxibustion record symptoms, and some laws summarized have been absorbed and used for reference. It shows the positive significance of its exploration in clinical diagnosis and treatment. A system of differentiation and treatment of external and internal injuries with acupuncture has not been formed, even though the meridian theory of TCM has a long history with many areas being explored, such as diseases, acupoints, acupuncture methods and stimulation amount. Therefore, this paper starts from the academic development history of meridians, reviews and analyzes the contribution and limitations of TCM acupuncture and moxibustion in the diagnosis and treatment of internal injury, in order to enlighten the current study and understanding of TCM.
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Objective:To anylyze the combination rule of prescriptions containing Cmnamomi Mmulus in the book of Treatise on Typhoid and Miscellaneous Diseases based on tree analysis algorith method. Methods:By collecting prescriptions contain Cmnamomi Mmulus in the book of Treatise on Typhoid and Miscellaneous Diseases, and applying the tree analysis algorithm method on the Ancient and Modern Medical Case Cloud Platform to co-occurrence calculate each layer of the prescriptions, we got the hierarchical tree structure diagram of Cmnamomi Mmulus prescriptions. Results:79 prescriptions containing 96 medicines were included, which appeared 529 times, with 7 different functions. The medicines that are frequently appeared include Cmnamomi Mmulus, Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle, Zingiberis Rhizoma Recens, Jujubae Fructus, etc. The main effects include relieving the exterior, warming the meridians, warming yang and promoting diuresis. The tree structure diagram of the prescription is divided into seven layers, including the largest items of Cmnamomi Mmulus, Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle,Zingiberis Rhizoma Recens, Jujubae Fructus, Paeoniae Radix Alba, Ephedrae Herba, Puerariae Lobatae Radix, and the collateral drugs of Poria, Atractylodis macrocephalae rhizoma, Alismatis Rhizoma, Zingiberis Rhizoma, etc. Conclusion:The formula tree analysis algorithm can connect the correlation between drugs in series, and show the relationship between a series of high-frequency co-occurrence drugs in the formula, which can be used for the learning of classics.
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The international TCM clinical knowledge database is demand-oriented, fully integrated TM resources of the Institute of Information on Traditional Chinese Medicine of China Academy of Chinese Medical Sciences that has accumulated for decades, with increased new resources. The resources are structured by subject indexing, classification and knowledge extraction, and are hierarchically translated by machine translation and manned proofreading. In addition, the research group also designs and develops service platform using ontology, semantic web, association relationship and other information technology. The knowledge database will provide knowledge service to TCM practitioners and the general public worldwide, and promote the internationalization of TCM.
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Objective:To analyze the medication rules of modern physicians on treating depression syndrome, so as to provide reference for clinical treatment of depression syndrome.Methods:We collect and sort out the modern medical records of depression syndrome in the cloud platform of ancient and modern medical records (v1.5) and the modern medical records' database of famous doctors, and search CNKI, Chongqing VIP and Wanfang databases for the modern depression medical cases from journals during database establishment time to October 1, 2018. We extracted traditional Chinese medicine prescription data in the medical records, and applied the ancient and modern medical records cloud platform (v 1.5) to standardize the acquired TCM data, and integrate data mining function for frequency statistics, cluster analysis, association analysis and complex network analysis to obtain the high frequency of drugs' attributes, classification, and common drug pairs and core prescriptions of modern doctors. Results:After screening, a total of 1 984 cases were included, 3 618 cases were diagnosed, and 3 089 pieces of data of TCM prescriptions were included. A total of 1 458 medicines were involved, and the total frequency of medication was 39 634. The high frequency medicines were: Bupleurum chinense (1 546 times), Poria cocos (1 210 times), Angelica sinensis (1 167 times), Paeonia lactiflora (1 109 times) and Tulip (1 091 times). The commonly used Chinese medicines were mainly warm, flat, bitter and bitter, mostly attributed to the four meridians of spleen, lung, liver and heart. Commonly used medicines were Radix Paeoniae Alba- Bupleurum, Radix Angelicae- Bupleurum, Radix Bupleurum- Tulip, Radix Angelicae- Paeoniae Alba, Radix Angelicae- Paeoniae Alba- Bupleurum, etc. The core prescriptions were Suanzaoren Decoction, Chaihu- Shugan San and Erchen Decoction. Conclusions:Modern physicians' treating principles for depression syndrome is soothing liver and regulating qi, invigorating spleen and nourishing heart, emphasizing qi and blood, harmonizing liver, spleen and heart, and linking TCM pathogeneses.
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With the rapid development of science and technology, more creative methods have been applied to the inheritance mode of traditional Chinese medicine, such as studying the inheritance process of famous doctorsin an objective and rigorous way. The bottleneck of information transmission from famous doctors is to collect data, process data, apply algorithms, analyze and summarize data. The integration of artificial intelligence and big data deep learning algorithm knowledge mapping technology and other technical methods has brought technological innovation for the inheritance of famous doctors. With such development, the team of the research center of TCM grand health intelligence, Institute of Information on Chinese Medicine, China Academy of Chinese Medical Science, has carried out a series of professional application system research in the field of traditional Chinese medicine, centering on the planning and inheritance of famous doctors. We developed the ancient and modern medical case cloud platform, medical big data analysis platform, cloud medical APP, and famous doctor inheritance workstation. In such way, the problems were solved of low efficiency of medical case collection and the lack of objective data support and information barriers in the experience summary of famous doctors. The artificial intelligence techniques are to promote the inheritance of famous doctors' experience and improve the teaching ability and efficiency.
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Objective@#The number of confirmed and suspected cases of the COVID-19 in Hubei province is still increasing. However, the estimations of the basic reproduction number of COVID-19 varied greatly across studies. The objectives of this study are 1) to estimate the basic reproduction number (R0) of COVID-19 reflecting the infectiousness of the virus and 2) to assess the effectiveness of a range of controlling intervention.@*Method@#The reported number of daily confirmed cases from January 17 to February 8, 2020 in Hubei province were collected and used for model fit. Four methods, the exponential growth (EG), maximum likelihood estimation (ML), sequential Bayesian method (SB) and time dependent reproduction numbers (TD), were applied to estimate the R0.@*Result@#Among the four methods, the EG method fitted the data best. The estimated R0 was 3.49 (95% CI: 3.42-3.58) by using EG method. The R0 was estimated to be 2.95 (95%CI: 2.86-3.03) after taking control measures.@*Conclusion@#In the early stage of the epidemic, it is appropriate to estimate R0 using the EG method. Meanwhile, timely and effective control measures were warranted to further reduce the spread of COVID-19.
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Objective The number of confirmed and suspected cases of the COVID-19 in Hubei province is still increasing. However, the estimations of the basic reproduction number of COVID-19 varied greatly across studies. The objectives of this study are 1) to estimate the basic reproduction number ( R 0 ) of COVID-19 reflecting the infectiousness of the virus and 2) to assess the effectiveness of a range of controlling intervention. Method The reported number of daily confirmed cases from January 17 to February 8, 2020 in Hubei province were collected and used for model fit. Four methods, the exponential growth (EG), maximum likelihood estimation (ML), sequential Bayesian method (SB) and time dependent reproduction numbers (TD), were applied to estimate the R 0 . Result Among the four methods, the EG method fitted the data best. The estimated R 0 was 3.49 (95% CI : 3.42-3.58) by using EG method. The R 0 was estimated to be 2.95 (95% CI : 2.86-3.03) after taking control measures. Conclusion In the early stage of the epidemic, it is appropriate to estimate R 0 using the EG method. Meanwhile, timely and effective control measures were warranted to further reduce the spread of COVID-19.
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Objective@#To evaluate the effect of the "Interner Plus-based AIDS Comprehensive Prevention Service System" among MSM in Guangzhou, during 2010-2017, using a dynamic compartmental model.@*Methods@#A dynamic compartmental model was developed to describe the HIV situation among MSM in Guangzhou. This model was parameterized on data from published literature or surveillance programs from the Guangzhou CDC. The Matlab 7.0 software was used for coding and analysis on collected data. HIV prevalence was analyzed among MSM under the status quo data and estimated the impact by the "Internet Plus" AIDS prevention services project.@*Results@#HIV prevalence would have increased to 22.75% in 2017, and the total number of new HIV infections would have been 11 038, from 2010 to 2017, using the data status quo. Under the Guangzhou "Internet Plus" AIDS prevention services project, the prevalence of HIV among MSM from 2010 to 2017 was estimated to be 8.44%, 9.68%, 10.65%, 11.34%, 11.73%, 11.83%, 11.71% and 11.43% in Guangzhou, which were similar to the surveillance data. The total number of new infections in the past 8 years under the "Internet Plus" scenario was estimated to be 4 009. The "Internet Plus" program would have prevented 7 029 (63.68%) new infections during 2010-2017 as compared to the number, status quo.@*Conclusions@#The fitting result of dynamic compartmental model seemed more reasonable, which was applicable to predict HIV epidemic among MSM in Guangzhou, suggesting that the increase of HIV prevalence had been curbed since the "Internet Plus" project which was launched in 2010, and the "Interner Plus-based AIDS Comprehensive Prevention Service System" had achieved the purpose as planned, epidemiologically.
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Objective: To research the medication regularity of Chinese medicine on treating urinary tract infection based on the Ancient and Modern Consilia Cloud Platform to provide references for clinical treatment of urinary tract infection.Methods: The Ancient and Modern Consilia Cloud Platform was used to screen the consilia of Traditional Chinese Medicine for the treatment of urinary tract infection, the materials mainly come from books, journal articles, famous medical studios in the modern Chinese medicine case database. Screening, cleaning, standardizing consilia, and the standardized consilia database was set up. Statistical analysis, cluster analysis and complex networks were used to analysed the core prescription, the herb medicine frequency, the herb medicine four gas, the herb medicine five flavors, the herb medicine channel tropism and other regularity of Chinese medicine treatment of urinary tract infection, and displayed visually. Results: A total of 501 prescriptions were included, a total of 245 herb medicine were involved, and liquorice, poria, dianthus superbus and rehmannia were used more frequently. The tastes are cold, neutral, sweet taste, and bitter taste. Their channel tropisms mainly belong to lung and liver. The core prescriptions are based on Bazhengsan and Zhibaidihuangwan. Conclusion: Heat, dampness and diuretic herbs are used in the treatment of urinary tract infections in Chinese medicine, and nourishing yin and kidney, and relieving the stagnation of liver at the same time.Asthenic and sthenia syndrome, appearance and essence are also taken into account.
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Objective To establish a dynamic compartmental model to predict the impact of HIV testing and treatment and pre-exposure prophylaxis (PrEP) on the annual incidence of HIV infection in men who have sex with men (MSM) in China from 2018 to 2037.Methods A dynamic compartmental model was developed to describe the HIV epidemic in MSM in China.The model was parameterized using data from the literature available.We used MATLAB 7.0 software for data simulation and graphics rendering.We analyzed HIV transmission among MSM and estimated the impact of expanded HIV testing and treatment and PrEP on HIV elimination in MSM.Results Under the current policy,the number of new HIV infections would reach 770 000,the infection rate would reach 11.1％ and the incidence rate would reach 0.72/100 person years in MSM in the next 20 years.Under the 90％-90％-90％ goal,440 000 new infections (57.7％) would be reduced,the HIV infection rate would decline to 5.7％ and the incidence rate would decline to 0.24/100 person years in the next 20 years,but it is still unlikely to achieve the goal of HIV elimination.With 100％ PrEP compliance,the required PrEP coverage rates for achieving HIV elimination in the next 10,15 and 20 years would be 65％,32％ and 19％,respectively.Conclusion It is necessary to strengthen the comprehensive intervention in MSM,continue to expand HIV testing and treatment,and improve PrEP adherence and coverage to further control and eliminate the epidemic of HIV/AIDS in MSM.
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To screen and evaluate the TCM in the treatment of bronchial asthma. Methods Retrieved the journals from China National Knowledge Infrastructure, the Vip Database, Wanfang Data and the Chinese Biomedical Literature Database (Sino Med) . The time limitation ran from January 1, 1987 to December 31, 2016. Extracted the indicators of the assessment based on the evaluating and screening system of country feasible TCM technology. Results a total of 150 treatment techniques were screened.They mostly were Chinese compound formula or point-application therapy. The score was between 24.857 and 34.304. Application of evaluating and screening system of country feasible TCM technology can screen and evaluate the feasible technologiesin the treatment of remission phase of bronchial asthma.
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Objective: To establish a dynamic compartmental model to predict the impact of HIV testing and treatment and pre-exposure prophylaxis (PrEP) on the annual incidence of HIV infection in men who have sex with men (MSM) in China from 2018 to 2037. Methods: A dynamic compartmental model was developed to describe the HIV epidemic in MSM in China. The model was parameterized using data from the literature available. We used MATLAB 7.0 software for data simulation and graphics rendering. We analyzed HIV transmission among MSM and estimated the impact of expanded HIV testing and treatment and PrEP on HIV elimination in MSM. Results: Under the current policy, the number of new HIV infections would reach 770 000, the infection rate would reach 11.1% and the incidence rate would reach 0.72/100 person years in MSM in the next 20 years. Under the 90%-90%-90% goal, 440 000 new infections (57.7%) would be reduced, the HIV infection rate would decline to 5.7% and the incidence rate would decline to 0.24/100 person years in the next 20 years, but it is still unlikely to achieve the goal of HIV elimination. With 100% PrEP compliance, the required PrEP coverage rates for achieving HIV elimination in the next 10, 15 and 20 years would be 65%, 32% and 19%, respectively. Conclusion: It is necessary to strengthen the comprehensive intervention in MSM, continue to expand HIV testing and treatment, and improve PrEP adherence and coverage to further control and eliminate the epidemic of HIV/AIDS in MSM.
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Humans , Male , China , Goals , HIV , HIV Infections/transmission , Homosexuality, Male , Models, Theoretical , Pre-Exposure ProphylaxisABSTRACT
Objective This study aims to investigate the effect of geranylgeranyltransferaseⅠ (GGTase-Ⅰ) on the proliferation and growth of tongue squamous cancer cells. Methods Three small interfering RNAs (siRNAs) were designed on the basis of the GGTase-Ⅰ sequence in GeneBank. These siRNAs were then transfected into tongue squamous cancer cells Cal-27. The mRNA and protein expression of GGTase-Ⅰ and RhoA were examined by real-time quantitative polymerase chain reaction and Western blotting, respectively. The expression of Cyclin D1 and p21 were examined by Western blotting. The proliferation and growth ability were analyzed by cell counting kit-8 assay and flow cytometry. Results The mRNA and protein expression of GGTase-Ⅰ in Cal-27 was reduced significantly after the GGTase-Ⅰ siRNAs were transfected (P<0.05). No significant difference in RhoA mRNA and protein expression was detected (P>0.05). Cyclin D1 expression decreased, whereas p21 expression increased significantly. The cell cycle was altered, and the growth-proliferative activity was inhibited (P<0.05). Conclusion GGTase-Ⅰ siRNA can inhibit the expression of GGTase-Ⅰ and the proliferative activity of tongue squamous cancer cells. GGTase-Ⅰ may be a potential target for gene therapy in tongue squamous cell cancer.
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Objective To investigate the effect of the language intervention to reduce patients′discomfort during a colonoscopy examination. Methods A total of 72 subjects who accepted a colonoscopy process in the Digestive Endoscopy Department of the Dalian Central Hospital from September 2014 to December 2015 were divided by random number table method into two groups, 38 for the control group and 34 for the observation group. The control group adopted routine nursing care, while the observation group adopted the language intervention besides the routine nursing care, in accordance with the implementation steps of language intervention for patients who accepted the colonoscopy examination, which means the four stages , the four positions and the four methods. The first stage: the enteroscope entered the anus and arrived the rectum , applied the deep breathing with anal movement method . The second stage: from the rectum to the sigmoid colon, used the induce distraction method. The third stage: stimulated the patients′ excitement at the junctional area of descending colon and transverse colon (the spleen area). The fourth stage: at the junctional area of transverse and ascending colon (the liver ares), used the continuous excitation method. In each stage, individualized language intervention and psychological nursing were given to every patient in the observation group. The cooperating effect of the two groups were evaluated. Results The frequency of pain, the pain scores,the frequency of pressing and the average insertion time of the control group respectively were (8.68 ± 0.83) times,(45.08 ± 6.66) points, (5.73±0.75) times,(372.26±31.77) s, while the observation group were (4.53±0.38) times,(17.07± 3.01) times,(2.05±0.38) times,(268.61±14.51) s, less than the control group ,the t value respectively were 3.81,27.17,3.51,4.66, and the difference was significant (P<0.01 or 0.05). Conclusions Using the language intervention nursing method can significantly relieve the patients′ nervous and anxiety during the procedure, ease the pain and discomfort, shorten the insertion time, improve the subjects′ experience during the colonoscopy examination, make the patients more coordinate with the examination and complete it successfully.
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Objective To assess the application value of trans-vaginal ultrasound and real-time sono-elastography in assessing the risk of preterm birth in pregnant women. Methods A total of 108 pregnant women who received prenatal examination at Beijing Obstetrics and Gynecology Hospital from January to November 2017 were included. Based on the presence of threatened premature or preterm labor or not, they were divided into a study group (n=29, with threatened premature or preterm labor) and a control group (n=79, with no threatened premature or preterm labor). Cervical length (CL) was measured by trans-vaginal ultrasound, and the following three cervical elasticity indexes were obtained by sono-elastography: the entire cervical strain rate (CS), the internal cervical os strain rate (IS), and external cervical os strain rate (ES). Independent samples t-test was used to analyze the difference in the above indexes between the two groups. Receiver operating characteristic (ROC) curve analysis was performed to assess the value of the above indexes in predicting the risk of preterm birth.Results CL was significantly lower[(2.94±0.66)cm vs(3.91±0.71)cm]and IS was significantly higher [(0.53±0.28)% vs (0.47±0.20)%] in the study group than in the control group (t=6.436, 3.406,both P<0.05).CS and ES in the study group were higher than those in the control group[(0.40±0.30)% vs (0.24±0.19)%,(0.74±0.39)% vs(0.73±0.37)%],but the differences were not statistically significant(t=1.365, 0.207, both P>0.05). ROC curve analysis indicated that CL, CS, IS, and ES performed differently in assessing the risk of preterm birth in pregnant women [area under the ROC curve (AUC): 0.156, 0.558, 0.689, 0.499]. The AUCs of CS and IS were greater than 0.50, and the AUC of IS was larger than those of other indexes. Using 0.30% as a cut-off for IS, its sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 66.7%, 79.3%, 71.1%, 55.4%, and 80.2%, respectively. Conclusions Cervical tissue elasticity indexes obtained by sono-elastography can be used to assess pregnant women at different gestational ages and predict the risk of preterm birth feasibly. IS is more useful than other indexes in predicting early or asymptomatic preterm birth.