1.Factors associated with depression after mild acute ischaemic stroke in the elderly and their predictive value
Yongming ZOU ; Rui SHU ; Na WANG ; Ji BIAN ; Lingya QIAO ; Xiaolin XU
Chinese Journal of Geriatrics 2024;43(3):291-296
Objective:To examine the risk factors and predictive value of depression following mild acute ischemic stroke in elderly individuals.The aim is to enhance early identification and intervention, ultimately leading to improved prognosis.Methods:A case-control study was conducted on 988 elderly patients with mild acute ischemic stroke.The study collected general population and social data, as well as clinical laboratory data such as blood glucose, blood lipids, and AD7C-NTP in urine.Additionally, the patients underwent assessments using the Montreal Cognitive Assessment Scale(MoCA), National Institutes of Health Stroke Scale(NHISS), Barthel index(BI), Hamilton Anxiety Scale(HAMA), and Hamilton Depression Scale(HAMD).Based on the HAMD depression scale score, the patients were divided into a nopost-stooke depression(NPSD)group and a post-stooke depression(PSD)group.The study then analyzed the related risk factors and predictive value of PSD.Results:A total of 988 patients were eligible for inclusion, with 132 being excluded and 856 being included.The NPSD and PSD groups showed significant differences in age, hypertension, smoking history, education level, and stroke history(all P<0.05).Regarding clinical data, there were statistically significant differences between the two groups in total cholesterol(TC), triacylglycerol(TG), HDL, urinary AD7C-NTP, MoCA, and HAMA scores(all P<0.05).The results of the multi-factor logistic regression analysis revealed that gender( OR=1.975, 95% CI: 1.223-3.190, P=0.005), stroke history( OR=1.352, 95% CI: 0.877-2.086, P=0.042), and HAMA score( OR=1.216, 95% CI: 0.932-1.526, P=0.043)were identified as independent risk factors for post-stroke depression in the elderly.Conversely, MoCA score( OR=0.873, 95% CI: 0.814-0.937, P<0.001)was found to be an independent protective factor.Furthermore, the ROC curve analysis demonstrated that the HAMA score(AUC=0.892, sensitivity: 0.721, specificity: 0.854, cut-off value: 9.5)exhibited significant predictive value, while the other indexes had limited predictive value. Conclusions:Gender, stroke history, and HAMA score have been identified as potential independent risk factors for post-stroke depression(PSD)in the elderly, while MoCA score may serve as an independent protective factor.Notably, HAMA score demonstrates a strong predictive ability for PSD.Early identification of these factors and timely intervention could significantly contribute to improving prognosis.
2.Distribution of urinary tract pathogens and susceptibility to nenofloxacin and levofolxacin in patients with community-acquired urinary tract infection
Zhen DU ; Shan CHEN ; Liang CUI ; Huiling WU ; Zhan GAO ; Jin YANG ; Gang CUI ; Jiajing WANG ; Tiehuan SHU ; Ninghan FENG ; Ludong QIAO
Chinese Journal of Urology 2024;45(1):24-28
Objective:To investigate the distribution characteristics of urinary tract pathogens in patients with community-acquired urinary tract infection and their sensitivity to nenoxacin and levofloxacin.Methods:This prospective, multicenter clinical trial included patients with community-acquired urinary tract infection who were admitted to urological clinics at 9 clinical research centers from November 2021 to August 2022.Inclusion criteria: Patients aged 18-70 years with community-acquired acute uncomplicated cystitis(AUC), recurrent acute episodes of urinary tract infection(rUTI), and non-febrile complicated urinary tract infection(cUTI) with signs of urinary tract irritation and abnormal elevation of routine white blood cells in urine. Exclusion criteria: ①Patients who received effective antimicrobial therapy within 72 h before enrollment and lasted for more than 24 h. ②Fever (>37.3℃) or symptoms of upper urinary tract infection such as low back pain, tapping pain in the kidney area, etc. ③Indwelling urinary catheter. At the first visit, clean midstream urine samples were taken for bacterial culture, and the distribution characteristics of urinary pathogens of different types of urinary tract infections were analyzed. Extended spectrum β-lactamases (ESBLs) were measured for Gram-negative bacteria. The susceptibility of nenoxacin and levofloxacin to urinary tract pathogens was determined by disk diffusion method. Drug resistance rate, sensitivity rate were analyzed between different disease groups.Results:There were 404 enrolled patients from 9 hospitals, including 364 (90.1%) females and 40 (9.9%) males. A total of 177 strains of pathogenic bacteria were isolated, among which the highest proportion of Escherichia coli was 66.1% (117/177).Klebsiella pneumoniae was followed by 6.8% (12/177) and Streptococcus agalactis 5.1% (9/177). The bacterial spectrum distribution of AUC and rUTI were similar, and the proportions of Escherichia coli were 70.6% (85/119) and 65.9% (29/44), respectively. However, the proportions of Escherichia coli isolated from cUTI patients were only 28.6% (4/14) and Enterococcus faecalis 7.1%(1/14). The overall detection rate of ESBLs in Gram-negative bacteria was 30.9%(43/139). The sensitivity rate of nenoxacin was 74.6%(91/122), and the resistance rate was 25.4%(31/122). The overall sensitivity rate of levofloxacin was 44.9%(70/156) and the resistance rate was 36.5%(57/156). The rate of resistance of urinary tract pathogens to levofloxacin was 48.2% (27/56) in patients with previous urinary tract infection history, and 30.0% (30/100) in patients with no previous urinary tract infection history, the difference was statistically significant( P=0.023).The sensitivity rate of Gram-negative bacteria to nenofloxacin was 70.7% (65/92) and that to levofloxacin was 50.0% (46/92, P<0.001). The sensitivity of Gram-positive bacteria to nenofloxacin was 80.0% (16/20), and that to levofloxacin was 70.0% (14/20, P=0.009). Conclusions:The bacterial profile of out-patient community acquired urinary tract infection varies greatly according to different diseases. The proportion of Escherichia coli in AUC and rUTI patients is higher than that in cUTI. The detection rate of ESBLs in Gram-negative bacteria was lower than the domestic average.Patients with a history of urinary tract infection had a high risk of treatment failure with levofloxacin. The sensitivity of common urinary tract pathogens to nenofloxacin was higher than levofloxacin.
3.Contralateral mandibular outer cortex "sandwich" bone grafting for correcting lower facial asymmetry with normal occlusal relationship
Guoping WU ; Tong LU ; Yuming QU ; Sheng GAO ; Zhiyang XIE ; Kaili YAN ; Chongxu QIAO ; Shunchao YAN ; Shu WANG ; Wensong SHANGGUAN
Chinese Journal of Plastic Surgery 2024;40(10):1049-1058
Objective:To investigate the clinical outcomes of using autologous mandibular outer cortex "sandwich" grafting to augment mandible for correcting lower facial asymmetry with normal occlusal relationships.Methods:A retrospective analysis was conducted on the clinical data of patients with lower facial asymmetry treated at the Department of Plastic Surgery, the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University, from January 2016 to December 2019. Preoperative cone-beam CT (CBCT) scans of the maxillofacial region were obtained to acquire three-dimensional data of the maxillofacial skeleton. Computer-aided design was used to determine the osteotomy range of the mandibular outer cortex and design osteotomy guide template. The outer cortex of the larger mandibular side (donor site) was harvested according to the osteotomy guide template and sectioned. The segmented mandibular outer cortex was then contoured to match the arc of the recipient side’s mandibular outer cortex and fixed to the inner side of the recipient mandibular outer cortex, thus increasing the width and thickness of the expanded mandible. Follow-up was conducted at 7th day and 6 months postoperatively, CBCT scan was performed to measure the changes in ramus height (Co-Go), mandibular body length (Go-Me), and mandibular outer cortex thickness, and volume, and the patient satisfaction with facial appearance (1 to 5 points, with higher scores indicating higher satisfaction), were assessed to evaluate surgical outcomes. Statistical analysis was performed using SPSS 12.0 software. Paired t-tests were used to compare patient satisfaction scores preoperatively and six months postoperatively. Repeated measurement ANOVA was used to compare Co-Go and Go-Me measurements preoperatively, 7th day, and 6 months postoperatively. If a statistically significant difference is found, further analysis using post-hoc testing(Tukey’s HSD test) will be conducted to examine the data. Results:Sixteen patients with lower facial asymmetry were included, comprising of 5 males and 11 females, aged 18 to 40 years, with an average age of 25.2 years. Surgical method included contralateral mandibular outer cortex "sandwich" grafting to the expanded mandible in 9 cases and simultaneous genioplasty in 7 cases. Follow-up ranged from 6 months to 5 years, with an average follow-up of 18.6 months. All patients experienced numbness of the lower lip postoperatively, which resolved within six months, and no severe complications occurred. The symmetry of lower facial contour improved significantly and remained stable. Patient satisfaction score for facial appearance increased from (1.63±0.62) points preoperatively to (4.19±0.75) points six months postoperatively( P<0.01). The differences in Co-Go on the donor side and Go-Me on the recipient side across the three time points(preoperatively, 7th day and 6 months postoperatively) were not statistically significant(all P>0.05). However, the differences in Go-Me on the donor side and Co-Go on the recipient side across the three time points were statistically significant(all P<0.05). On the donor side, the mandibular outer cortex thickness decreased by a maximum of 6 mm on 7th day postoperatively and increased by a maximum of 2 mm at 6 months postoperatively compared to 7th day. On the recipient side, mandibular outer cortex thickness increased by a maximum of 6 mm on 7th day postoperatively and decreased by a maximum of 2 mm at six months postoperatively compared to 7th day. The volume of the mandibular outer cortex on the recipient side increased by (4 415.94±1 017.21)mm 3 at 7th day postoperatively compared to preoperatively, and decreased by (202.63±300.85)mm 3 at 6 months postoperatively. Conclusion:For lower facial asymmetrical with normal occlusal relationships and no occlusal plane deviation, contralateral mandibular outer cortex "sandwich" bone grafting can effectively increase the width and volume of the mandible on the grafted side, achieving favorable clinical outcomes.
4.Effect mechanism of dihydromyricetin on the tumor biological characteristics of endometrial cancer cells
Wei-Hua CUI ; Jing-Ying SONG ; Shu-Xin QIAO ; Shu-Zhong DUAN
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1039-1043
Objective To explore the effects of dihydromyricetin on the proliferation,apoptosis,and invasion of endometrial cancer(EC)cells and its possible mechanisms.Methods Ishikawa cells in the logarithmic growth phase were taken and divided into the control group,20 μmol/L dihydromyricetin intervention group,40 μmol/L dihydromyricetin intervention group,and 80 μmol/L dihydromyricetin intervention group,which were treated with different final concentrations of dihydromyricetin(0 μmol/L,20 μmol/L,40 μmol/L,80 μmol/L).Then,CCK-8 assay and flow cytometry were used to detect the effects of dihydromyricetin on the cell proliferation and apoptosis.Transwell experiment was used to detect the effect of dihydromyricetin on the cell invasion.qRT-PCR and Western blot were used to detect the effects of dihydromyricetin on the cell expression of miR-21 and PTEN.Results Compared with the control group,the cell proliferation inhibition rate and apoptosis rate in the dihydromyricetin intervention group were significantly increased(P<0.05),and gradually increased with the increase of dihydromyricetin concentration(P<0.05).Compared with the control group,the numbers of migration and invasion cells in the dihydromyricetin intervention group were significantly decreased(P<0.05),and gradually decreased with the increase of dihydromyricetin concentration(P<0.05).Compared with the control group,the cell expression of miR-21 in the dihydromyricetin intervention group was significantly decreased(P<0.05),and gradually decreased with the increase of dihydromyricetin concentration(P<0.05),the expression levels of PTEN mRNA and protein were significantly increased(P<0.05),and gradually increased with the increase of dihydromyricetin concentration(P<0.05).Conclusion Dihydromyricetin can inhibit the growth and metastasis of EC cells,and the inhibitory effect is positively correlated with its concentration.The mechanism may be related to the effect of dihydromyricetin on the miR-21/PTEN signaling pathway of EC cells.
5.Mechanobiology of Long-distance Mitochondria Transport in Neuronal Axon
Hu-Cheng ZHAO ; Yan-Li SUN ; Shu-Le QIAN ; Xi-Qiao FENG
Progress in Biochemistry and Biophysics 2024;51(9):2028-2036
As polar cells, neurons are composed of a cell body, dendritic networks, and long, branched axons. To maintain normal physiological functions throughout the lifespan of vertebrates, differentiated neurons require substantial energy to sustain resting potential and synaptic transmission. Neurons predominantly rely on ATP generated through mitochondrial oxidative phosphorylation for energy. They transport and accumulate healthy mitochondria to energy-demanding areas, such as the presynaptic terminals of axon branches, through long-distance transport and anchoring, while reversing the transport of aged or damaged mitochondria in the axon terminals back to the soma for degradation. This article, integrating authors’ research, discusses from a mechanical perspective how mitochondria overcome resistance to achieve long-distance transport along axons under the influence of driving forces. The review covers topics such as microtubule polarity, microtubule motor proteins, mitochondrial docking protein complexes, interactions between mitochondria and anchoring proteins, intracellular resistance, interactions between mitochondria and the endoplasmic reticulum, and aspects of mitochondrial biogenesis, fission, fusion, division, and quality control. These novel perspectives will provide important insights for understanding neurological diseases caused by mitochondrial transport dysfunctions.
6.Contralateral mandibular outer cortex "sandwich" bone grafting for correcting lower facial asymmetry with normal occlusal relationship
Guoping WU ; Tong LU ; Yuming QU ; Sheng GAO ; Zhiyang XIE ; Kaili YAN ; Chongxu QIAO ; Shunchao YAN ; Shu WANG ; Wensong SHANGGUAN
Chinese Journal of Plastic Surgery 2024;40(10):1049-1058
Objective:To investigate the clinical outcomes of using autologous mandibular outer cortex "sandwich" grafting to augment mandible for correcting lower facial asymmetry with normal occlusal relationships.Methods:A retrospective analysis was conducted on the clinical data of patients with lower facial asymmetry treated at the Department of Plastic Surgery, the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University, from January 2016 to December 2019. Preoperative cone-beam CT (CBCT) scans of the maxillofacial region were obtained to acquire three-dimensional data of the maxillofacial skeleton. Computer-aided design was used to determine the osteotomy range of the mandibular outer cortex and design osteotomy guide template. The outer cortex of the larger mandibular side (donor site) was harvested according to the osteotomy guide template and sectioned. The segmented mandibular outer cortex was then contoured to match the arc of the recipient side’s mandibular outer cortex and fixed to the inner side of the recipient mandibular outer cortex, thus increasing the width and thickness of the expanded mandible. Follow-up was conducted at 7th day and 6 months postoperatively, CBCT scan was performed to measure the changes in ramus height (Co-Go), mandibular body length (Go-Me), and mandibular outer cortex thickness, and volume, and the patient satisfaction with facial appearance (1 to 5 points, with higher scores indicating higher satisfaction), were assessed to evaluate surgical outcomes. Statistical analysis was performed using SPSS 12.0 software. Paired t-tests were used to compare patient satisfaction scores preoperatively and six months postoperatively. Repeated measurement ANOVA was used to compare Co-Go and Go-Me measurements preoperatively, 7th day, and 6 months postoperatively. If a statistically significant difference is found, further analysis using post-hoc testing(Tukey’s HSD test) will be conducted to examine the data. Results:Sixteen patients with lower facial asymmetry were included, comprising of 5 males and 11 females, aged 18 to 40 years, with an average age of 25.2 years. Surgical method included contralateral mandibular outer cortex "sandwich" grafting to the expanded mandible in 9 cases and simultaneous genioplasty in 7 cases. Follow-up ranged from 6 months to 5 years, with an average follow-up of 18.6 months. All patients experienced numbness of the lower lip postoperatively, which resolved within six months, and no severe complications occurred. The symmetry of lower facial contour improved significantly and remained stable. Patient satisfaction score for facial appearance increased from (1.63±0.62) points preoperatively to (4.19±0.75) points six months postoperatively( P<0.01). The differences in Co-Go on the donor side and Go-Me on the recipient side across the three time points(preoperatively, 7th day and 6 months postoperatively) were not statistically significant(all P>0.05). However, the differences in Go-Me on the donor side and Co-Go on the recipient side across the three time points were statistically significant(all P<0.05). On the donor side, the mandibular outer cortex thickness decreased by a maximum of 6 mm on 7th day postoperatively and increased by a maximum of 2 mm at 6 months postoperatively compared to 7th day. On the recipient side, mandibular outer cortex thickness increased by a maximum of 6 mm on 7th day postoperatively and decreased by a maximum of 2 mm at six months postoperatively compared to 7th day. The volume of the mandibular outer cortex on the recipient side increased by (4 415.94±1 017.21)mm 3 at 7th day postoperatively compared to preoperatively, and decreased by (202.63±300.85)mm 3 at 6 months postoperatively. Conclusion:For lower facial asymmetrical with normal occlusal relationships and no occlusal plane deviation, contralateral mandibular outer cortex "sandwich" bone grafting can effectively increase the width and volume of the mandible on the grafted side, achieving favorable clinical outcomes.
7.Clinical application of thromboelastography in the prevention of lower extremity intermuscular venous thrombosis after knee arthroscopy
Zhongqing ZHANG ; Shu QIAO ; Mailashu WU ; Haonan CHI ; Pingping WANG ; Jinlei SUN
Chinese Journal of Blood Transfusion 2024;37(6):625-631
Objective To explore the guiding value of thromboelastography(TEG)in the formulation of personalized anticoagulation regimen after knee arthroscopy.Methods A total of 50 patients who underwent knee arthroscopy in our hos-pital from April to August 2023 were randomly divided into two groups.Twenty-seven patients with routine anticoagulation were selected as the control group,and 23 patients with personalized anticoagulation were selected as the experimental group.Conventional anticoagulation was a prophylactic dose of low molecular weight heparin calcium(LMWHC)selected according to body weight,once a day to 7 days after surgery.Personalized anticoagulation was performed according to the prophylactic dose of LMWHC until postoperative day 3.On postoperative day 3,LMWHC was changed to aspirin according to the TEG return index(MA>70 mm,α Angle>72°,K value<1 min),and the initial prophylactic dose was 100 mg/d.LMWHC was changed to rivaroxaban when R<5 min,and the prophylactic dose was 10 mg/d until postoperative day 7.Pa-tients with hypocoagulation or subcutaneous ecchymosis stopped the drug first,and if it was further aggravated,component blood transfusion was performed according to the TEG results.The difference of Caprini score in perioperative period,the correlation between TEG and CCT on postoperative day 1,and the accuracy of predicting thrombosis on postoperative day 7 were compared between the two groups using the receiver operating characteristic curve(ROC).Results There was a sig-nificant difference in Caprini score between the two groups at 7 days after operation(P<0.05),suggesting that the adjust-ment of anticoagulant drugs in the experimental group was effective at 3 days after operation.Pearson correlation evaluation showed that there was a strong positive correlation between maximum coagulation intensity(MA)in TEG and platelet(Plt)in CCT at day 1 after surgery(P<0.05).Thrombosis was found in the control group at 7 days after operation,all of which were CMVT and disappeared after therapeutic antithrombotic therapy.MA was included in the ROC curve for model analysis.The area under the ROC curve(AUC)of the control group was 0.819,and the AUC of the experimental group was 0.508.It was found that the control group model had higher accuracy in predicting the formation of CMVT.Conclusion Individu-alized anticoagulation under TEG monitoring can effectively reduce the occurrence of CMVT after knee arthroscopy,which has guiding value for anticoagulation and thrombosis prevention.
8.A Study on the Characteristics of Articulation Movement in Patients with Dysarthria under Different Vowel Tasks
Jiamei CHEN ; Qin WAN ; Jiajing LIANG ; Fenfen HUI ; Hongfen QIAO ; Wenzhuo SHU
Journal of Audiology and Speech Pathology 2024;32(5):413-417
Objective To investigate the acoustic characteristics of monophthong vowels and compound vow-els articulation movement in patients with dysarthria.Methods A total of 24 patients aged 40~81 years old with dysarthria from hospitals,and 24 healthy adults aged 40~80 years old from communities in Shanghai were recrui-ted.The first and second formants(F1,F2)of monophthong vowels/a/,/i/,/u/were extracted from the speech samples,and mandibular distance,tongue distance,vowel space area(VSA)and vowel articulation index(VAI)were calculated.The slope of the second formant of compound vowels/ai/,/ua/,/uai/was extracted and calculat-ed.The acoustic parameters of two groups of subjects were compared under different tasks.Results Under the monophthong vowels task,F1 of/a/,F2 of/i/,mandibular distance,tongue distance,VSA and VAI in the pa-tients were significantly lower than those in the control group(P<0.01).F2 of/u/was significantly higher than that in the control group(P<0.01).F2 slope of/ai/,/ua/,/uai/was significantly lower than that of the control group(P<0.05).Conclusion The space of monophthong vowels articulation movement was reduced in the pa-tients with dysarthria,presenting a state of aggregation.The speed of compound vowels articulation movement was decreased.
9.Study on the Safety and Influencing Factors of Home Medication for Elderly Patients with Chronic Diseases in Urban Areas of Henan:A Cross-sectional Survey
Huiyan MA ; Zhigang ZHAO ; Chunfeng QIAO ; Shu GE ; Boya ZHOU ; Xixi LI ; Mingfen WU
Herald of Medicine 2024;43(12):1951-1957
Objective To evaluate the status of home medication safety among elderly patients with chronic diseases and analyze its influencing factors in urban and rural areas of Henan Province.Methods Convenient sampling method was adopted.Data was collected through a designed and optimized questionnaire.Pharmacists conducted in-home surveys.Excel and SPSS 26.0 software were used for data analysis.Results A total of 352 valid questionnaires were analyzed.Most respondents were aged 60~70 years,with a female proportion of 56.2%,and 52.0%of them had a junior high school education or lower.The top-ranked chronic diseases were hypertension(62.2%)and hyperlipidemia(33.2%),and 61.1%of patients suffered from multiple chronic diseases.Antipyretic and analgesic drugs were most common in home medicine cabinets(90.1%).The proportion of drugs being stored in accordance with the instructions(46.9%)was slightly low,and 93.8%of the elderly handled expired drugs improperly.Awareness of medication guidance services was low(34.9%).Logistic regression analysis showed that factors such as education level and monthly income had significant effects on the understanding of drug package insert,rational drug storage,proper disposal of expired drugs,and awareness of medication guidance services(P<0.05).Conclusion There are still some potential safety risks in the home medication use of elderly patients with chronic diseases in urban and rural areas of Henan Province.It is necessary to enhance education on drug storage and medication guidance,particularly for low-income and less-educated groups,to improve the safety of home medication use.
10.Epidemiological and clinical characteristics of healthcare-associated infec-tion in neonates with different gestational ages and birth weights
Yan-Min LI ; Li-Li PING ; Xiao-Lei MA ; Yu-Qiao DIAO ; Shu-Fen ZHAI ; Rui-Min ZHANG
Chinese Journal of Infection Control 2024;23(9):1119-1125
Objective To understand the epidemiological and clinical characteristics of healthcare-associated infec-tion(HAI)in neonates with different gestational ages and birth weights,and provide guidance for personalized cli-nical diagnosis and treatment.Methods According to the inclusion and exclusion criteria,240 neonates with HAI in the neonatal intensive care unit(NICU)of a hospital in Handan City from January 2018 to December 2022 were selected as the study group,720 neonates without HAI were selected as the control group based on systematic sam-pling method with a ratio of 1∶3.The incidence of HAI,distribution characteristics of infection site,pathogenic features of HAI,as well as the effect of different delivery modes on HAI in neonates with different gestational ages and birth weights were analyzed.Results Neonates with gestational age<28 weeks and birth weight<1 000 g had the highest incidence of HAI,which were 19.48%and 20.41%,respectively.Among neonates with gestational age<28 weeks,unidentified site infection were the most(37.50%),while in all gestational age groups within 28-36+6 weeks,bloodstream infection(BSI)and respiratory system infection were predominant.For neonates with gestational age ≥37 weeks,BSI and unidentified site infection occurred frequently.Among neonates in all weight groups,BSI was the most frequent,followed by respiratory system infection.Pathogens from different sites of in-fections in neonates with different gestational ages and birth weights varied.Among neonates with gestational age of 28-31+6 weeks and birth weight of 1 000-1 499 g,the constituent of birth modes showed statistically significant difference between neonates with and without HAI(both P<0.05).Conclusion Epidemiological and clinical chara-cteristics of HAI in neonates with different gestational ages and birth weights are different.For the prevention and control of HAI,individualized diagnosis and treatment plans should be developed to achieve precise prevention and control,reduce the incidence of HAI,and improve the overall treatment level of neonates.

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