1.Social media content analysis of public and private Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency facebook groups
Ebner Bon G. Maceda ; Michelle E. Abadingo ; Bubbles Beverly N. Asor ; Rizza Kaye C. Cases ; Renchillina Joy G. Supan ; Kia S. Anarna ; Patricia Carla A. Libo-on ; Theodore Delfin C. Vesagas ; Ma-Am Joy R. Tumulak
Acta Medica Philippina 2024;58(Early Access 2024):1-12
		                        		
		                        			Background:
		                        			As social media continue to grow as popular and convenient tools for acquiring and disseminating health information, the need to investigate its utilization by laypersons encountering common medical issues becomes increasingly essential.
		                        		
		                        			Objectives:
		                        			This study aimed to analyze the content posted in Facebook groups for Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency and how these engage the members of the group.
		                        		
		                        			Methods:
		                        			This study employed an inductive content analysis of user-posted content in both public and private Facebook groups catering specifically to G6PD deficiency. The G6PD Facebook groups with 10 or more posts within the past 12 months were selected for this study. Data were harvested from posts and comments using ExportComment.
		                        		
		                        			Results:
		                        			A total of 46 G6PD-related Facebook groups were identified. Of which, 19 were public and 27 were private groups, with an average membership of 5000-6000 accounts. After eligibility based on criteria and authorization for private groups, 3 public and 3 private groups were included, with the majority of these groups focused on sharing information. Five main themes of posted content were identified: diagnosis, management, beliefs, psychosocial factors, and medical requirements. “Diagnosis”-related posts referred to conversations about the causes and symptoms of G6PD, “management” referred to medication or diet, “beliefs” involved traditional or lay perceptions, “psychosocial factors” referred to posts that disclosed how psychosocial factors influenced G6PD deficiency practices, and “medical requirements” referred to documentation regarding
the condition. The bulk of these posts used three strategies for communication: information-requesting,
self-disclosure, and promotion of products/services. Information requests were the most common.
		                        		
		                        			Conclusion
		                        			The results of the study showed opportunities and challenges in health education on G6PD, especially in evaluating the credibility and accuracy of the information given and received. Looking at the content and manner of communicating information noted, the newborn screening program may improve its advocacy and education campaign, and may develop targeted educational materials and effective dissemination strategies that could clarify, explain, or refute information and beliefs mostly shared on these platforms.
		                        		
		                        		
		                        		
		                        			Glucosephosphate Dehydrogenase Deficiency
		                        			;
		                        		
		                        			 Self-Help Groups
		                        			
		                        		
		                        	
2.Social media content analysis of public and private Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency Facebook groups
Ebner Bon G. Maceda ; Michelle E. Abadingo ; Bubbles Beverly N. Asor ; Rizza Kaye C. Cases ; Renchillina Joy G. Supan ; Kia S. Anarna ; Patricia Carla A. Libo-on ; Theodore Delfin C. Vesagas ; Ma-am Joy R. Tumulak
Acta Medica Philippina 2024;58(22):65-76
BACKGROUND
As social media continue to grow as popular and convenient tools for acquiring and disseminating health information, the need to investigate its utilization by laypersons encountering common medical issues becomes increasingly essential.
OBJECTIVESThis study aimed to analyze the content posted in Facebook groups for Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency and how these engage the members of the group.
METHODSThis study employed an inductive content analysis of user-posted content in both public and private Facebook groups catering specifically to G6PD deficiency. The G6PD Facebook groups with 10 or more posts within the past 12 months were selected for this study. Data were harvested from posts and comments using ExportComment.
RESULTSA total of 46 G6PD-related Facebook groups were identified. Of which, 19 were public and 27 were private groups, with an average membership of 5000-6000 accounts. After eligibility based on criteria and authorization for private groups, 3 public and 3 private groups were included, with the majority of these groups focused on sharing information. Five main themes of posted content were identified: diagnosis, management, beliefs, psychosocial factors, and medical requirements. “Diagnosis”-related posts referred to conversations about the causes and symptoms of G6PD, “management” referred to medication or diet, “beliefs” involved traditional or lay perceptions, “psychosocial factors” referred to posts that disclosed how psychosocial factors influenced G6PD deficiency practices, and “medical requirements” referred to documentation regarding the condition. The bulk of these posts used three strategies for communication: information-requesting, self-disclosure, and promotion of products/services. Information requests were the most common.
CONCLUSIONThe results of the study showed opportunities and challenges in health education on G6PD, especially in evaluating the credibility and accuracy of the information given and received. Looking at the content and manner of communicating information noted, the newborn screening program may improve its advocacy and education campaign, and may develop targeted educational materials and effective dissemination strategies that could clarify, explain, or refute information and beliefs mostly shared on these platforms.
Glucosephosphate Dehydrogenase Deficiency ; Self-help Groups ; Social Media
3.Successful thrombolysis and mechanical thrombectomy in an early pregnant woman with protein S deficiency and arterial ischemic stroke: A case report
Ma. Ericka S. Del Mundo ; Diana-lynn Que ; Remy Margarette Berroya-Moreno
Philippine Journal of Neurology 2024;27(2):16-21
Protein S deficiency causing arterial ischemic stroke during pregnancy is uncommon. Delay or omission of treatment with perfusion therapies may worsen outcomes for both the mother and the fetus. In this paper, we report a case of an early pregnant woman with protein S deficiency and multiple history of chronic cerebrovascular disease who underwent successful thrombolysis and mechanical thrombectomy. The patient is a 35-year-old woman, eight weeks pregnant, with a history of protein S deficiency and chronic cerebrovascular disease, presenting with rightsided weakness and aphasia. Initial National Institutes of Health Stroke Scale was 10 with cranial magnetic resonance imaging findings of acute infarcts on the left caudate, lentiform nucleus, insula, and frontal lobe with a large vessel occlusion on the proximal M1 segment of the left middle cerebral artery. Intravenous thrombolysis and mechanical thrombectomy were performed with complete recanalization. The patient improved and delivered without any complications after 8 months. Protein S deficiency can contribute to arterial thrombosis including ischemic stroke. Arterial ischemic stroke and large vessel occlusion can cause significant disability if not treated appropriately. Reperfusion therapies in pregnant women show favorable outcomes and should be performed if the benefits outweigh the risks.
Human ; Female ; Adult: 25-44 Yrs Old ; Arteries ; Ischemic Stroke ; Thrombectomy ; Protein S ; Protein S Deficiency ; Pregnant Women
4.Effect of vitamin D supplementation on inflammatory bowel disease in children: A meta-analysis
Jan Pofer A. Mantos ; Portia Menelia D. Monreal ; Rebecca A. Castro ; Caroline Anne A. Castro
Journal of Medicine University of Santo Tomas 2023;7(1):1060-1070
		                        		
		                        			Background:
		                        			Apart from its role in bone health, recent developments have shown that vitamin D also has anti-inflammatory properties, and therefore may have a role in inflammatory bowel disease (IBD) in children.
		                        		
		                        			Objectives:
		                        			To determine the effect of vitamin D supplementation on the disease activity of pediatric patients with IBD.
		                        		
		                        			Design:
		                        			Random-effects meta-analysis
		                        		
		                        			Data Sources: :
		                        			Studies were searched at Cochrane Library, PubMed, EBSCO Host, ScienceDirect, Google Scholar, and Wiley Online.
		                        		
		                        			Review Methods:
		                        			Experimental studies measuring the effect of vitamin D on the disease activity of pediatric patients with IBD were included. The proportion of disease activity, measured as remission rate or inactivity using Pediatric Crohn’s Disease Activity Index (PCDAI) or Pediatric Ulcerative Colitis Activity Index (PUCAI), and the mean and standard deviation of mean serum vitamin D [25(OH)D] level, change in 25(OH)D, and different inflammatory markers [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] were extracted or estimated and recorded in an abstraction form. Standardized mean difference and odds ratio were used as summary effect measures and estimated using Stata/Multiprocessor.
		                        		
		                        			Results:
		                        			The serum 25(OH)D (SMD = 1.75, z = 2.33, p = 0.001) and change in 25(OH)D (SMD = 3.37, z = 2.34, p = 0.019) was significantly higher among those who received a high dose of vitamin D. However, a significantly high heterogeneity was estimated (I2 >50%). For the disease activity of IBD, the standard mean difference of mean ESR (SMD = –1.10, z = 5.35, p = 0.001) was significantly lower with high-dose vitamin D. The likelihood of remission rate using the Pediatric Crohn’s Disease Activity Index (PCDAI) or Pediatric Ulcerative Colitis Activity Index (PUCAI), and standardized mean difference of CRP were not significantly different among those who received high-dose and low-dose vitamin D.
		                        		
		                        			Conclusion
		                        			Cognizant of the functions of vitamin D in enhancing intestinal flora balance, regulating immunologic response, and improving intestinal mucosal barrier, vitamin D can be recommended as a supplementary treatment for IBD among the pediatric population. Nevertheless, there is still insufficient evidence for the cut-off level of adequate levels of serum 25(OH)D among pediatric patients with IBD, thus necessitating further studies.
		                        		
		                        		
		                        		
		                        			Vitamin D Deficiency
		                        			
		                        		
		                        	
5.Pseudo-orthostatic tremor as a manifestation of vitamin B12 deficiency: A case report
Journal of Medicine University of Santo Tomas 2023;7(1):1186-1189
		                        		
		                        			
		                        			Vitamin B12 deficiency has long been known to present with various neurological manifestations, but only rarely presents as movement disorders, especially in adults. We present the case of a 30-year-old vegan male presenting with tremors on both legs when standing which was relieved by vitamin B12 supplementation. To the best of our knowledge, this is the first documented case of slow orthostatic tremor or pseudo-orthostatic tremor caused by vitamin B12 deficiency. 
		                        		
		                        		
		                        		
		                        			Vitamin B 12 Deficiency
		                        			;
		                        		
		                        			 Vitamin B 12
		                        			;
		                        		
		                        			 Vegans
		                        			;
		                        		
		                        			 Movement Disorders
		                        			;
		                        		
		                        			 Tremor
		                        			;
		                        		
		                        			 Electromyography
		                        			
		                        		
		                        	
6.Clinical symptoms and distribution characteristics traditional Chinese medicine syndromes of pulmonary nodules.
Yue LI ; Xin-Yue ZHANG ; Shu-Lin HE ; Yuan-Chen ZHAO ; Rui LIU ; Bao-Jin HUA
China Journal of Chinese Materia Medica 2023;48(17):4782-4788
		                        		
		                        			
		                        			A cross-sectional study method combined with two types of traditional Chinese medicine(TCM) syndrome differentiation methods was adopted to investigate the clinical symptoms and distribution characteristics of TCM syndromes in patients with pulmonary nodules from the perspectives of number, size, nature, and stability of pulmonary nodules by using the χ~2 test, systematic clustering and Apriori algorithm correlation analysis. The common clinical symptoms of pulmonary nodules were fatigue(77.35%) and irritability(75.40%), and 40 symptoms were clustered into 3 groups(digestive system symptoms, respiratory system symptoms, and emotional and systemic symptoms) and 8 major symptom categories. The proportion of cold and heat in complexity syndrome(63.43%) was higher based on cold-heat syndrome differentiation. The top two syndromes were Qi deficiency syndrome(88.03%) and Qi depression syndrome(83.17%) based on disease syndrome differentiation. Yang deficiency syndrome(60.52%) was more than Yin deficiency syndrome(50.16%). There were higher proportions of phlegm syndrome(78.67%) and Yang deficiency syndrome(69.33%) of so-litary pulmonary nodules in terms of the number of pulmonary nodules. In terms of size, the proportion of phlegm syndrome decreased as the mean diameter of pulmonary nodules increased, while the proportions of Yang deficiency syndrome and blood stasis syndrome increased. The distribution of Qi depression syndrome was more in those with mean diameter<10 mm(85.02%, P=0.044) and cold syndrome was more in those with mean diameter ≥10 mm(16.67%, P=0.024). In terms of the nature of pulmonary nodules, the proportions of Qi depression syndrome and heat syndrome decreased with the increase in solid components of pulmonary nodules, while the proportions of Yin deficiency syndrome and cold and heat in complexity syndrome increased. The blood stasis syndrome accounted for a higher proportion of pulmonary nodules with solid components. In terms of the stability of pulmonary nodules, dampness syndrome(72.97%), blood stasis syndrome(37.84%), and cold and heat in complexity syndrome(70.27%) accounted for higher proportions. In addition, patients with new nodules presented higher proportions in Qi inversion syndrome(52.00%, P=0.007) and cold and heat in complexity syndrome(66.00%, P=0.008). Meanwhile, 11 syndromes were associated and 4 common compound syndromes were obtained(Qi deficiency and depression syndrome, Qi depression and phlegm coagulation syndrome, Qi deficiency and phlegm coagulation syndrome, and Qi deficiency and dampness obstruction syndrome). Qi deficiency syndrome and Qi depression syndrome could be associated with other syndromes. The results show that the main clinical symptoms of pulmonary nodules are fatigue and irritability. The main TCM syndromes of pulmonary nodules are Qi deficiency syndrome, Qi depression syndrome, Yang deficiency syndrome, and cold and heat in complexity syndrome. The distribution of TCM syndromes is significantly correlated with the size of pulmonary nodules and the presence or absence of new nodules. The common compound syndromes are Qi deficiency and depression syndrome, Qi depression and phlegm coagulation syndrome, Qi deficiency and phlegm coagulation syndrome, and Qi deficiency and dampness obstruction syndrome.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Medicine, Chinese Traditional
		                        			;
		                        		
		                        			Yin Deficiency/diagnosis*
		                        			;
		                        		
		                        			Yang Deficiency/diagnosis*
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			Syndrome
		                        			
		                        		
		                        	
7.Mechanism of Zhenwu Decoction in improving renal inflammatory injury in mice with DN of spleen-kidney Yang deficiency syndrome by regulating ROCK/IKK/NF-κB pathway.
Yu-Qiu JIN ; Guang-Shun CHEN ; Min BAI ; Zhe ZHAO ; Yan-Xu CHEN ; Meng-Yuan TIAN ; Jia-Lian CHEN ; Qing-Sheng WANG ; Zhen-Hua LIU
China Journal of Chinese Materia Medica 2023;48(18):5041-5048
		                        		
		                        			
		                        			To investigate the intervention effect and mechanism of Zhenwu Decoction on diabetic nephropathy(DN) mice of spleen-kidney Yang deficiency syndrome based on the Rho-associated coiled-coil kinase(ROCK)/IκB kinase(IKK)/nuclear factor-κB(NF-κB) pathway. Ninety-five 7-week-old db/db male mice and 25 7-week-old db/m male mice were fed adaptively for one week. The DN model of spleen-kidney Yang deficiency syndrome was induced by Dahuang Decoction combined with hydrocortisone by gavage, and then the model was evaluated. After modeling, they were randomly divided into a model group, high-dose, medium-dose, and low-dose Zhenwu Decoction groups(33.8, 16.9, and 8.45 g·kg~(-1)·d~(-1)), and an irbesartan group(25 mg·kg~(-1)·d~(-1)), with at least 15 animals in each group. The intervention lasted for eight weeks. After the intervention, body weight and food intake were measured. Serum crea-tinine(Scr), blood urea nitrogen(BUN), fasting blood glucose(FBG), urinary albumin(uALb), and urine creatinine(Ucr) were determined. The uALb/Ucr ratio(ACR) and 24 h urinary protein(UTP) were calculated. Renal pathological morphology was evaluated by HE staining and Masson staining. The levels of key molecular proteins in the ROCK/IKK/NF-κB pathway were detected by Western blot. Enzyme-linked immunosorbent assay(ELISA) was used to detect interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Compared with the blank group, the model group showed increased content of BUN, uALb, and SCr, increased values of 24 h UTP and ACR, decreased content of Ucr(P<0.05), enlarged glomeruli, thickened basement membrane, mesangial matrix proliferation, inflammatory cell infiltration, and collagen fiber deposition. The protein expression of ROCK1, ROCK2, IKK, NF-κB, phosphorylated IKK(p-IKK), phosphorylated NF-κB(p-NF-κB), and phosphorylated inhibitor of NF-κB(p-IκB) increased(P<0.05), while the protein expression of inhibitor of NF-κB(IκB) decreased(P<0.05). The levels of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α increased(P<0.05), while the level of IL-10 decreased(P<0.05). Compared with the model group, the groups with drug treatment showed decreased levels of BUN, uALb, SCr, 24 h UTP, and ACR, increased level of Ucr(P<0.05), and improved renal pathological status to varying degrees. The high-and medium-dose Zhenwu Decoction groups and the irbesartan group showed reduced protein expression of ROCK1, ROCK2, IKK, NF-κB, p-IKK, p-NF-κB, and p-IκB in the kidneys(P<0.05), increased protein expression of IκB(P<0.05), decreased levels of serum inflammatory factors IL-1β, IL-6, IL-8, and TNF-α(P<0.05), and increased level of IL-10(P<0.05). Zhenwu Decoction can significantly improve renal function and renal pathological damage in DN mice of spleen-kidney Yang deficiency syndrome, and its specific mechanism may be related to the inhibition of inflammatory response by down-regulating the expression of key molecules in the ROCK/IKK/NF-κB pathway in the kidney.
		                        		
		                        		
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			NF-kappa B/metabolism*
		                        			;
		                        		
		                        			Interleukin-8
		                        			;
		                        		
		                        			Interleukin-10
		                        			;
		                        		
		                        			Tumor Necrosis Factor-alpha/metabolism*
		                        			;
		                        		
		                        			Interleukin-6
		                        			;
		                        		
		                        			I-kappa B Kinase
		                        			;
		                        		
		                        			Spleen
		                        			;
		                        		
		                        			Irbesartan
		                        			;
		                        		
		                        			Uridine Triphosphate
		                        			;
		                        		
		                        			Yang Deficiency/drug therapy*
		                        			;
		                        		
		                        			Kidney/pathology*
		                        			
		                        		
		                        	
8.Gender differences in antidepressant effect of raw Rehmanniae Radix.
Xiao-Hui WU ; Jun-Ming WANG ; Ling-Yu QIN ; Tian-Zhu ZHANG ; Ya-Min LI ; Yue-Yue ZHANG ; Bing-Yu LONG ; Qing-Wen HE ; Li-Jie JI ; Ling-Ling SONG
China Journal of Chinese Materia Medica 2023;48(19):5326-5336
		                        		
		                        			
		                        			For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Yin Deficiency
		                        			;
		                        		
		                        			NLR Family, Pyrin Domain-Containing 3 Protein
		                        			;
		                        		
		                        			Sex Factors
		                        			;
		                        		
		                        			Cyclooxygenase 2
		                        			;
		                        		
		                        			NF-kappa B
		                        			;
		                        		
		                        			Antidepressive Agents/pharmacology*
		                        			
		                        		
		                        	
9.Anti-fatigue effect of Lubian on kidney Yin deficiency and kidney Yang deficiency mice and mechanism based on PI3K-Akt pathway.
Xiang-Shan WANG ; Ying-Li ZHU ; Mei-Yu LYU ; Yan CHEN ; Shu-Hui YU ; Wei-Qian WANG ; Jian-Jun ZHANG ; Chun WANG ; Hong-Shun GU ; Lin-Yuan WANG
China Journal of Chinese Materia Medica 2023;48(11):3032-3038
		                        		
		                        			
		                        			This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Phosphatidylinositol 3-Kinases/genetics*
		                        			;
		                        		
		                        			Proto-Oncogene Proteins c-akt/genetics*
		                        			;
		                        		
		                        			Liver Glycogen
		                        			;
		                        		
		                        			Yang Deficiency/drug therapy*
		                        			;
		                        		
		                        			Yin Deficiency/drug therapy*
		                        			;
		                        		
		                        			Kidney
		                        			;
		                        		
		                        			Body Weight
		                        			
		                        		
		                        	
10.Analysis of F12 gene variants and molecular mechanisms in patients with coagulation factor Ⅻ deficiency.
Shuai FANG ; Jia YANG ; Xialin ZHANG ; Linhua YANG ; Gang WANG
Chinese Journal of Medical Genetics 2023;40(4):429-434
		                        		
		                        			OBJECTIVE:
		                        			To analyze the sequence of the F12 gene and molecular mechanism for 20 patients with coagulation factor Ⅻ (FⅫ) deficiency.
		                        		
		                        			METHODS:
		                        			The patients were selected from the outpatient department of the Second Hospital of Shanxi Medical University from July 2020 to January 2022. The activity of coagulation factor Ⅷ (FⅧ:C), factor Ⅸ (FⅨ:C), factor Ⅺ (FⅪ:C) and factor Ⅻ (FⅫ:C) were determined by using a one-stage clotting assay. All exons and 5' and 3' UTR of the F12 gene were analyzed by Sanger sequencing to detect the potential variants. Bioinformatic software was used to predict the pathogenicity of the variants, conservation of amino acids, and protein models.
		                        		
		                        			RESULTS:
		                        			The FⅫ:C of the 20 patients has ranged from 0.07% to 20.10%, which was far below the reference values, whilst the other coagulation indexes were all normal. Sanger sequencing has identified genetic variants in 10 patients, including 4 with missense variants [c.820C>T (p.Arg274Cys), c.1561G>A (p.Glu521Lys), c.181T>C (p.Cys61Arg) and c.566.G>C (p.Cys189Ser)], 4 deletional variants c.303_304delCA(p.His101GlnfsX36), 1 insertional variant c.1093_1094insC (p.Lys365GlnfsX69) and 1 nonsense variant c.1763C>A (p.Ser588*). The remaining 10 patients only harbored the 46C/T variant. The heterozygous c.820C>T(p.Arg274Cys) missense variant in patient 1 and the homozygous c.1763C>A (p.Ser588*) nonsense variant in patient 2 were not included in the ClinVar and the Human Gene Mutation Database. Bioinformatic analysis predicted that both variants were pathogenic, and the corresponding amino acids are highly conserved. The protein prediction models suggested that the c.820C>T (p.Arg274Cys) variant may affect the stability of the secondary structure of FⅫ protein by disrupting the original hydrogen bonding force and truncating the side chain, leading to changes in the vital domain. c.1763C>A (p.Ser588*) may produce a truncated C-terminus which may alter the spatial conformation of the protein domain and affect the serine protease cleavage site, resulting in extremely reduced FⅫ:C.
		                        		
		                        			CONCLUSION
		                        			Among individuals with low low FⅫ:C detected by one-stage clotting assay, 50% have harbored variants of the F12 gene, among which the c.820C>T and c.1763C>A were novel variants underlying the reduced coagulating factor FⅫ.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Factor XII/genetics*
		                        			;
		                        		
		                        			Pedigree
		                        			;
		                        		
		                        			Mutation
		                        			;
		                        		
		                        			Mutation, Missense
		                        			;
		                        		
		                        			Heterozygote
		                        			;
		                        		
		                        			Factor XII Deficiency/genetics*
		                        			
		                        		
		                        	
            

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