1.Clinical Evidence Profile of Eleven Expensive Chinese Patent Medicines: A Scoping Analysis
Yajing LI ; Miaomiao LI ; Le ZHANG ; Wenya WANG ; Hui ZHAO ; Xing LIAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):227-238
ObjectiveThis study employed the scoping review method to systematically retrieve and analyze the basic information and clinical research evidence of expensive Chinese patent medicines (CPMs), aiming to provide a basis for future related research and clinical applications. MethodsEight Chinese and English databases were systematically searched for the clinical research evidence on expensive CPMs. ResultsEleven expensive CPMs (Angong Niuhuang Wan, Jufang Zhibao Wan, Suhexiang Wan, Pien Tze Huang, Niuhuang Qingxin Wan, Qinggong Shoutao Wan, Compound Realgar Natural Indigo Tablets, Xihuang Wan, Dingkun Wan, Babao Wan, and Guilingji Capsules) were selected. A total of 365 related studies were included in this review, comprising 331 clinical studies (of which 291 were randomized controlled trials), 30 systematic reviews and Meta-analyses, 3 expert consensus, and 1 rapid health technology assessment. Among the 11 CPMs, 2(Angong Niuhuang Wan and Jufang Zhibao Wan) had a daily price over 500 yuan. The famous and precious Chinese medicinal materials involved included Moschus (frequency of 7), Bovisc Alculus (7), and Borneol (5). The dosage forms included pills, capsules, oral liquid, tablets, and lozenges. The diseases treated by these CPMs mainly included malignant tumors, cerebrovascular diseases, gynecological diseases, and hepatobiliary system diseases. The sample sizes of the clinical studies were mainly concentrated within the range of 51-100 cases, and the main control form was CPM + basic Western medicine treatment vs. basic Western medicine treatment. The 331 clinical studies reported a total of 44 adverse events occurred, of which 36 were determined to be adverse reactions. ConclusionThe scarcity of raw materials leads to the high prices of expensive CPMs. The difficulty of conducting clinical research and the critical and severe cases treated lead to a lack of clinical research evidence with large sample sizes. The uneven distribution of existing studies, incomplete information on medicine package, and non-standard clinical research designs remain to be addressed in the future.
2.A qualitative study on the experiences of nutrition impact symptoms in esophageal cancer patients
Muxi CHENG ; Huiyan LIAO ; Hui LI ; Yuxin HE ; Lei ZHONG ; Xinhui SONG ; Mei LI
Chinese Journal of Nursing 2025;60(19):2378-2383
Objective To explore the real experiences of nutrition impact symptoms in esophageal cancer patients during diagnosis and treatment,and to provide references for developing nutritional management strategies.Methods Using purposive sampling,15 esophageal cancer patients admitted to the thoracic surgery department of a tertiary grade A hospital in Guangzhou from October to December 2024 were selected for semi-structured interviews.Thematic analysis was used for data analysis.Results 4 themes and 12 sub-themes were identified:①Multiple symptom perceptions:esophageal obstruction-dysphagia,appetite-affecting symptoms,multiple symptom over-lap,and individual differences in symptom perception.② Insufficient symptom cognition:overestimation of symptom controllability and biased symptom attribution.③ Negative emotional reactions:anxiety and fear about eating,frustration with declining eating function,and helplessness and guilt about losing control over eating.④ Di-verse symptom coping strategies:avoidance coping,adaptive coping,and active nutritional management.Conclusion The nutrition impact symptom experiences of esophageal cancer patients are complex and diverse.Healthcare professionals should promptly identify and assess nutrition impact symptoms,provide nutrition health education,strengthen psychological guidance,and develop culturally distinctive individualized nutritional management strategies.
3.A Case Report of Mitochondrial Diabetes Mellitus Caused by Large Fragment Deletion of Mitochondrial Gene and Literature Review
Ran LI ; Jinhao LIAO ; Hanhui FU ; Hui PAN ; Yuxiu LI ; Jiangfeng MAO ; Hongbo YANG ; Huabing ZHANG
Medical Journal of Peking Union Medical College Hospital 2025;16(3):634-640
Mitochondrial diabetes mellitus(MDM)is a genetically heterogeneous disorder caused by mitochondrial DNA(mtDNA)or nuclear DNA mutations,characterized by multi-system involvement and diverse clinical phenotypes.We report a pediatric case presenting with growth retardation followed by subsequent development of diabetes mellitus.Systematic evaluation revealed concurrent bilateral sensorineural hearing loss,bilateral basal ganglia calcification,and electroencephalographic abnormalities.A post-exercise lactate test demonstrated significant elevation of serum lactate levels immediately after physical exertion.Genetic analysis identified a large-scale mitochondrial DNA deletion spanning from m.8649 to m.16084.This case re-port is complemented by a literature review focusing on the pathogenesis,genetic characteristics,and therapeu-tic approaches of mitochondrial diabetes,with particular emphasis on mitochondrial disorders exhibiting large-scale mtDNA deletions alongside diabetic manifestations.Our comprehensive analysis aims to enhance clinical understanding and inform diagnostic strategies for this complex disease entity.
4.Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults (version 2025)
Bobin MI ; Faqi CAO ; Weixian HU ; Wu ZHOU ; Chenchen YAN ; Hui LI ; Yun SUN ; Yuan XIONG ; Jinmi ZHAO ; Qikai HUA ; Xinbao WU ; Xieyuan JIANG ; Dianying ZHANG ; Zhongguo FU ; Dankai WU ; Guangyao LIU ; Guodong LIU ; Tengbo YU ; Jinhai TAN ; Xi CHEN ; Fengfei LIN ; Zhangyuan LIN ; Dongfa LIAO ; Aiguo WANG ; Shiwu DONG ; Gaoxing LUO ; Zhao XIE ; Dong SUN ; Dehao FU ; Yunfeng CHEN ; Changqing ZHANG ; Kun LIU ; Deye SONG ; Yongjun RUI ; Fei WU ; Ximing LIU ; Junwen WANG ; Meng ZHAO ; Biao CHE ; Bing HU ; Chengjian HE ; Guanglin WANG ; Xiao CHEN ; Guandong DAI ; Shiyuan FANG ; Wenchao SONG ; Ming CHEN ; Guanghua GUO ; Yongqing XU ; Lei YANG ; Wenqian ZHANG ; Kun ZHANG ; Xin TANG ; Hua CHEN ; Weiguo XU ; Shuquan GUO ; Yong LIU ; Xiaodong GUO ; Zhewei YE ; Liming XIONG ; Tian XIA ; Hongbin WU ; Qisheng ZHOU ; Mengfei LIU ; Yiqiang HU ; Yanjiu HAN ; Hang XUE ; Kangkang ZHA ; Wei CHEN ; Zhiyong HOU ; Bin YU ; Jiacan SU ; Peifu TANG ; Baoguo JIANG ; Guohui LIU
Chinese Journal of Trauma 2025;41(5):421-432
Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.
5.Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures (version 2025)
Bolong ZHENG ; Wei MEI ; Yanzheng GAO ; Liming CHENG ; Jian CHEN ; Qixin CHEN ; Liang CHEN ; Xigao CHENG ; Jian DONG ; Jin FAN ; Shunwu FAN ; Xiangqian FANG ; Zhong FANG ; Shiqing FENG ; Haoyu FENG ; Haishan GUAN ; Yong HAI ; Baorong HE ; Lijun HE ; Yuan HE ; Hua HUI ; Weimin JIANG ; Junjie JIANG ; Dianming JIANG ; Xuewen KANG ; Hua GUO ; Jianjun LI ; Feng LI ; Li LI ; Weishi LI ; Chunde LI ; Qi LIAO ; Baoge LIU ; Xiaoguang LIU ; Xuhua LU ; Shibao LU ; Bin LIN ; Chao MA ; Xuexiao MA ; Renfu QUAN ; Limin RONG ; Honghui SUN ; Tiansheng SUN ; Yueming SONG ; Hongxun SANG ; Jun SHU ; Jiacan SU ; Jiwei TIAN ; Xinwei WANG ; Zhe WANG ; Zheng WANG ; Zhengwei XU ; Huilin YANG ; Jiancheng YANG ; Liang YAN ; Feng YAN ; Guoyong YIN ; Xuesong ZHANG ; Zhongmin ZHANG ; Jie ZHAO ; Yuhong ZENG ; Yue ZHU ; Rongqiang ZHANG
Chinese Journal of Trauma 2025;41(9):805-818
Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.
6.Factors and optimization strategies of low normal fertilization in spindle transfer of mouse oocytes
Linlin YANG ; Xiaoyu LIAO ; Wenjuan WANG ; Hui MIAO ; Na LI ; Huiling BI ; Congxiu MIAO
Chinese Journal of Reproduction and Contraception 2025;45(5):482-488
Objective:To explore the factors that tend to lead to a low normal fertilization rate in spindle transfer of mouse oocytes and its strategies.Methods:Oocytes in metaphase Ⅱ (MⅡ) of C57BL/6 and ICR strains mouse were obtained for observations of mitochondrial replacement operations. Spindle karyoplasts of three different sizes (large, medium, small) were isolated by micromanipulation, and their morphology was observed under bright field and polarized light at 0 min, 10 min, 20 min and 30 min after suction. For small spindle karyoplasts, 2% paraformaldehyde fixation was performed after 10 min, 20 min and 30 min respectively, and the morphology of spindle and chromosomes was observed after immunofluorescence staining. Intracytoplasmic sperm injection (ICSI) was performed on oocytes, followed by small spindle karyoplasts isolation, and then fusion was conducted after 30 min (traditional method), 10 min (modified method 1) and 0 min (modified method 2) respectively. ICSI-oocytes without spindle transfer were used as control group, and 14-16 h later, the fertilization of reconstructed oocytes was observed and statistically analyzed.Results:1) When spindle karyoplast was just retrieved (0 min), the karyoplast membrane was smooth and complete, and the spindle showed a normal spindle shape. After 10 min, 20 min and 30 min of suction, the karyoplast membrane was twisted or elongated with an irregular morphology, and the spindle was also twisted, stretched or scattered with a weaker brightness. And the smaller spindle karyoplast, the more serious the deformation was. 2) When the spindle was just taken out (0 min), immunofluorescence staining showed that the spindle was in a standard spindle shape, and the chromosomes were regularly and neatly arranged on the equatorial plate. With the prolongation of placement time, spindles were elongated and tapered or dumbbell-shaped, and chromosomes were scattered and irregularly arranged. 3) For the traditional method of spindle transfer, the normal fertilization rate of C57BL/6 mouse reconstructed oocytes was 63.16% (24/38), which was statistically different from that of control group ( P=0.002). The normal fertilization rate [68.00% (34/50)] in the modified method 1 group was significantly lower than that in control group [90.00% (36/40), P=0.019], but there was no statistical difference with the traditional method ( P=0.260). However, the normal fertilization rate [82.50% (33/40)] in the modified method 2 group was similar to control group ( P=0.422), and was significantly higher than that of the traditional method group ( P=0.010). Conclusion:The longer the spindle karyoplast of mouse oocytes is stayed after retrieval, the more serious the morphological changes, the more unstable the spindles and chromosomes, and the lower normal fertilization rate. Immediate fusion of spindle karyoplast after isolation is the best time for mitochondrial replacement micromanipulation.
7.Study on the Clinical Value of NLR,PLR,CAR Dynamic Monitoring in the Acute Phase of Kawasaki Disease
Wei LI ; Hui-ying LIAO ; Mei-qing LI ; Guo-hui TANG
Progress in Modern Biomedicine 2025;25(19):3122-3130
Objective:To observe the clinical value of neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),C-reactive protein(CRP)to albumin(ALB)ratio(CAR)dynamic monitoring in the acute phase of Kawasaki disease(KD).Methods:This study was a single-center prospective study,146 in the acute phase of KD patients who were admitted to The Third Affiliated Hospital of Guangdong Medical University from June 2022 to September 2024 were selected as the study subjects(KD group).Hospitalized patients with fever ≥ 3 days received during the same period(fever control group,n=146)and healthy children underwent physical examination(healthy control group,n=146)were seleted.According to the differences in response to intravenous immunoglobulin treatment,KD patients were divided into two subgroups:immunoglobulin insensitive group(n=21)and immunoglobulin sensitive group(n=125).According to the presence or absence of coronary artery injury(CAL),KD patients were divided into two subgroups:non CAL group(n=97)and CAL group(n=49).According to alanine aminotransferase(ALT)expression level,KD patients were divided into two subgroups:non liver injury group(ALT value<80 U/L,n=110)and liver injury group(ALT value ≥ 80 U/L,n=36).NLR,PLR,and CAR of KD group,fever control group,and healthy control group were compared.NLR,PLR,and CAR were compared at admission,before and 3 d after immunoglobulin infusion between the immunoglobulin sensitive group and immunoglobulin insensitive group,liver injury group and non liver injury group,CAL group and non CAL group.Receiver operating characteristic(ROC)curve was used to evaluate diagnostic efficacy.Result:NLR,PLR,and CAR of the KD group and fever control group were higher than those of the healthy control group,and the KD group were higher than those of the fever control group(P<0.05).NLR,PLR,and CAR of the immunoglobulin insensitive group were higher than those of the immunoglobulin sensitive group at admission,before and 3 d after immunoglobulin infusion(P<0.05).NLR,PLR,and CAR of the liver injury group were higher than those of non liver injury group at admission,before and 3 d after immunoglobulin infusion(P<0.05).NLR,PLR,and CAR of the CAL group were higher than those of the non CAL group at admission,before and 3 days after immunoglobulin infusion(P<0.05).When NLR,PLR,and CAR were used alone or in combination at admission,the area under curve(AUC)(95%CI)of ROC values were 0.798(0.715~0.869),0.802(0.717~0.871),0.833(0.752~0.896),and 0.935(0.873~0.973),respectively,among them,the combination had the highest diagnostic efficacy.Conclusion:NLR,PLR,and CAR are all abnormally elevated in KD patients,and which are associated with patient immunoglobulin sensitivity,liver injury and CAL.The combination detection of the above three indicators has better diagnostic efficacy for KD.
8.Effects of miR-34b-5p on atherosclerosis-associated foam cell formation and inflammatory response by targeting IGFBP1 expression
Hui HUI ; Guangpeng WU ; Mei LIAO ; Guangzhi LI
Chinese Journal of Immunology 2025;41(4):879-884
Objective:To investigate the role of miR-34b-5p in formation of atherosclerosis(AS)-associated foam cells and in-flammation,and its possible mechanism.Methods:Expression levels of miR-34b-5p and insulin-like growth factor binding protein-1(IGFBP1)mRNA in serum of 34 AS patients and 20 healthy controls were detected.RAW264.7 macrophages were treated with oxi-dized low-density lipoprotein(ox-LDL)to construct AS foam cell model,and expression levels of miR-34b-5p and IGFBP1 mRNA in foam cells were detected.Interaction between miR-34b-5p and IGFBP1 was verified by dual luciferase reporter gene assay.miR-34b-5p inhibitor(inhibitor),inhibitor negative control(inhibitor-NC),IGFBP1 siRNA plasmid(si-IGFBP1)and siRNA negative control(si-NC)were separately or co-transfected into RAW264.7 macrophages.Lipid deposition ability of foam cells was observed,and levels of intracellular total cholesterol(TC),IL-1β,IL-6 and TNF-α were detected.Results:Compared with healthy controls,miR-34b-5p was highly expressed in serum of AS patients(P<0.05),while expression of IGFBP1 mRNA was lower(P<0.05).ox-LDL treatment significantly increased expression of miR-34b-5p(P<0.05),while significantly reduced expression of IGFBP1 mRNA in RAW264.7 macrophages(P<0.05).Dual luciferase reporter assay showed that IGFBP1 was the target gene of miR-34b-5p.Compared with inhibi-tor-NC group,expression of IGFBP1 protein in RAW264.7 macrophages in inhibitor group was increased significantly(P<0.05).After ox-LDL induction,miR-34b-5p inhibitor inhibited lipid deposition ability of macrophages,and decreased levels of intracellular TC,IL-1β,IL-6 and TNF-α.Interfering expression of IGFBP1 gene could reverse the intervention effect of miR-34b-5p inhibitor on macro-phages by enhance lipid deposition ability of macrophages,and increase levels of intracellular TC,IL-1β,IL-6 and TNF-α.Conclu-sion:Down-regulation of miR-34b-5p expression can inhibit the formation of AS-associated foam cells and inflammatory response,and the mechanism may be realized by targeting up-regulation of IGFBP1 expression.
9.Constructing an induction educational system for clinical rotations in standardized pediatric residency training: program development and outcome evaluation
Ying LIAO ; Wei BAI ; Shan LI ; Guo YU ; Danyu SONG ; Hui YAN
Chinese Journal of Medical Education Research 2025;24(4):440-445
Objective:To construct a multimodal induction educational system suitable for standardized pediatric residency training bases, and to evaluate its effectiveness, thereby obtaining suggestions for further improvement.Methods:Twelve residents newly enrolled in the 2023 standardized residency training program who commenced their first-year training were included as study subjects. The induction educational system comprised multiple modules: department introduction, training plan and assessment requirements, departmental workflow, routine diagnosis and treatment of major diseases, specialized skills/procedures, and lifestyle guidance. Training materials and methods were tailored to the characteristics of each training module. Checklists were used for supervision and review, and a competency checklist was designed to evaluate residents' mastery of the training at two weeks of induction, which would guarantee the effectiveness of the training. A questionnaire survey, powered by wjx.cn, was used to obtain the experience and suggestions from the residents and ward instructors on induction education, and content ranking analysis was performed on the survey results.Results:The survey revealed that, before starting a new rotation, residents' top three educational needs were departmental workflow, routine diagnosis and treatment of common diseases, and specialized skills/procedures. Residents preferred face-to-face lectures and demonstrations by attending physicians or senior residents; instructors suggested improving relevant materials (such as resident physician manuals and video materials) and face-to-face lectures. The residents considered the current induction educational system to be greatly beneficial in basic theories, treatment principles, basic skills, and auxiliary examination processes.Conclusions:Through the above research, a multimodal induction educational system suitable for the standardized pediatric residency training base in the Peking University First Hospital has been preliminarily established, and suggestions for further improvement have been obtained, which is conducive to further improving the system and residents' post competency.
10.National bloodstream infection bacterial resistance surveillance report 2023: Gram-positive bacteria
Chaoqun YING ; Jinru JI ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Jiangqin SONG ; Hui DING ; Yanyan LI ; Yuanyuan DAI ; Haifeng MAO ; Pengpeng TIAN ; Lu WANG ; Yongyun LIU ; Yizheng ZHOU ; Jiliang WANG ; Yan JIN ; Donghong HUANG ; Hongyun XU ; Peng ZHANG ; Xinhua QIANG ; Hong HE ; Lin ZHENG ; Junmin CAO ; Zhou LIU ; Ying HUANG ; Yan GENG ; Haiquan KANG ; Dan LIU ; Guolin LIAO ; Lixia ZHANG ; Fenghong CHEN ; Yanhong LI ; Baohua ZHANG ; Haixin DONG ; Xiaoyan LI ; Donghua LIU ; Qiuying ZHANG ; Xuefei HU ; Liang GUO ; Sijin MAN ; Dijing SONG ; Rong XU ; Youdong YIN ; Kunpeng LIANG ; Aiyun LI ; Zhuo LI ; Hongxia HU ; Guoping LU ; Jinhua LIANG ; Qiang LIU ; Yinqiao DONG ; Jilu SHEN ; Shuyan HU ; Liang LUAN ; Jian LI ; Ling MENG ; Dengyan QIAO ; Xiusan XIA ; Bo QUAN ; Dahong WANG ; Chunhua HAN ; Xiaoping YAN ; Fei LI ; Shifu WANG ; Ping SHEN ; Yunbo CHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2025;18(2):118-132
Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System(BRICS)during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute(CLSI). Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus( n=1 544,35.2%),coagulase-negative Staphylococci( n=1 441,32.9%), Enterococcus faecium( n=574,13.1%), Enterococcus faecalis( n=385,8.8%),and α-hemolytic Streptococci( n=187,4.3%). The prevalence of methicillin-resistant Staphylococcus aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococci(MRCNS)was 26.2%(405/1 544)and 69.8%(1 006/1 441),respectively. Notably,all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility(>97.0%)to cephalobiol,rifampicin,trimethoprim-sulfamethoxazole,linezolid,minocycline,tigecycline,and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium(resistance to vancomycin and teicoplanin:both 1.7%)compared to Enterococcus faecalis(both 0.3%). The detection rates of MRSA and MRCNS exhibited significant regional variations across the country( χ2=17.674 and 148.650,respectively,both P<0.001). No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA( χ2=14.111, P<0.001)and MRCNS( χ2=4.828, P=0.028)in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA( χ2=18.986, P<0.001)and MRCNS( χ2=4.477, P=0.034)in less developed regions(per capita GDP

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