1.Analysis of factors affecting renal function and surgical complications in recipients after living donor kidney transplantation
Dingran LI ; Jingcheng LÜ ; Yichen ZHU
Organ Transplantation 2026;17(1):77-85
Objective To explore factors affecting the postoperative renal function and surgical complications in recipients of living donor kidney transplantation. Methods A retrospective analysis was conducted on medical records of 119 patients who underwent living donor kidney transplantation at Beijing Friendship Hospital Affiliated to Capital Medical University, from January 2020 to September 2024. The severity of surgical complications was evaluated using the Clavien-Dindo score. Spearman correlation analysis was used to analyze the correlation between preoperative general data, surgical data, preoperative laboratory data and the Clavien-Dindo score. Multiple linear regression analysis was performed on the correlated factors. Univariate and multivariate logistic regression analyses were used to analyze the factors affecting the occurrence of delayed graft function (DGF) after surgery. Results The body mass index, history of hypertension, cold ischemia time, the first warm ischemia time, the second warm ischemia time, prothrombin activity and international normalized ratio were all correlated with the Clavien-Dindo score. Multiple linear regression analysis showed that the longer the second warm ischemia time and the first warm ischemia time were, the higher the Clavien-Dindo score was, and the more severe the postoperative surgical complications were (all P<0.05). Multivariate logistic regression analysis showed that long the first warm ischemia time and long dialysis time were independent risk factors for the occurrence of DGF after surgery (all P<0.05). Conclusions Prolonged the second warm ischemia time and the first warm ischemia time may increase the severity of surgical complications in recipients after living donor kidney transplantation. Long the first warm ischemia time and long dialysis time are independent risk factors for the occurrence of DGF after surgery.
2.Herbal Textual Research on Stemonae Radix in Famous Classical Formulas
Gang XU ; Li AN ; Xiaomei WANG ; Erhuan WANG ; Yichen YANG ; Cunde MA ; Yang YANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):241-251
This article systematically reviews and verifies the historical evolution of Stemonae Radix from the aspects of name, origin, harvesting and processing, quality and others by consulting ancient and modern literature, in order to provide reference for the development and utilization of famous classical formulas containing this medicinal herb. Stemonae Radix has a long history of application, and it derives its name from its distinctive growth pattern, featuring clusters of ten to several dozen underground tuberous roots. This morphology resembles that of certain plants in the genus Asparagus, leading to historical instances where tuberous roots from genus Asparagus were mistakenly used as Stemonae Radix. After the research, it can be concluded that Stemonae Radix was first recorded in Mingyi Bielu, and throughout history, Baidu has been recognized as its official name, though it also bears alternative names such as Baibing, Pofucao and Ye Tianmendong. The mainstream sources used throughout history have been the dried tuberous roots of Stemona sessilifolia, S. japonica or S. tuberosa from the family Stemonaceae. This aligns with the 2025 edition of Pharmacopoeia of the People's Republic of China(hereinafter referred to as Chinese Pharmacopoeia). Additionally, Asparagus filicinus and A. officinalis from the genus Asparagus are common sources of confusion with Stemonae Radix. The three primitive plants are mainly distributed in the Yangtze River basin and southern China, exhibiting a wide distribution. Historically, wild harvesting was predominant, but cultivation is now established. In ancient times, the harvesting time was mostly in the second, third, and eighth lunar months, when roots were harvested and dried. Nowadays, it is more common to pick and excavate in the spring and autumn seasons. After excavation, the roots are washed, fibrous roots removed, briefly blanched in boiling water or steamed until no white core remains, and then sun-dried or oven-dried. In ancient times, the processing of Stemonae Radix primarily involved roasting(stir-frying), wine roasting, or raw materials. Modern mainstream processing specifications include two types of raw and honey-roasted products. In terms of quality evaluation of the medicinal materials, ancient criteria of "preferring plump and moist roots" align with modern requirement favoring "thick, robust stems with firm texture". Evaluating quality with authenticity, since the Song dynasty, it has been highly praised to produce in Chuzhou and Hengyang as the best. It was an ancient method of fixing the production area to stabilize the medicinal origin, reflecting the ancient recognition of the therapeutic efficacy of plants belonging to the genus Stemona. The main functions of Stemonae Radix remain consistent throughout history, including relieving coughs, eliminating phlegm and parasites. Based on the research results, it is recommended that when developing famous classical formulas containing the medicinal material Stemonae Radix, the botanical source specified in the 2025 edition of Chinese Pharmacopoeia should be selected. The specific species can be determined according to the distribution of resources and the main production areas, and the origin and corresponding botanical source should be fixed. Processing methods should be chosen based on the prescription requirements. It is recommended to use raw products without specified requirements.
3.Herbal Textual Research on Stemonae Radix in Famous Classical Formulas
Gang XU ; Li AN ; Xiaomei WANG ; Erhuan WANG ; Yichen YANG ; Cunde MA ; Yang YANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):241-251
This article systematically reviews and verifies the historical evolution of Stemonae Radix from the aspects of name, origin, harvesting and processing, quality and others by consulting ancient and modern literature, in order to provide reference for the development and utilization of famous classical formulas containing this medicinal herb. Stemonae Radix has a long history of application, and it derives its name from its distinctive growth pattern, featuring clusters of ten to several dozen underground tuberous roots. This morphology resembles that of certain plants in the genus Asparagus, leading to historical instances where tuberous roots from genus Asparagus were mistakenly used as Stemonae Radix. After the research, it can be concluded that Stemonae Radix was first recorded in Mingyi Bielu, and throughout history, Baidu has been recognized as its official name, though it also bears alternative names such as Baibing, Pofucao and Ye Tianmendong. The mainstream sources used throughout history have been the dried tuberous roots of Stemona sessilifolia, S. japonica or S. tuberosa from the family Stemonaceae. This aligns with the 2025 edition of Pharmacopoeia of the People's Republic of China(hereinafter referred to as Chinese Pharmacopoeia). Additionally, Asparagus filicinus and A. officinalis from the genus Asparagus are common sources of confusion with Stemonae Radix. The three primitive plants are mainly distributed in the Yangtze River basin and southern China, exhibiting a wide distribution. Historically, wild harvesting was predominant, but cultivation is now established. In ancient times, the harvesting time was mostly in the second, third, and eighth lunar months, when roots were harvested and dried. Nowadays, it is more common to pick and excavate in the spring and autumn seasons. After excavation, the roots are washed, fibrous roots removed, briefly blanched in boiling water or steamed until no white core remains, and then sun-dried or oven-dried. In ancient times, the processing of Stemonae Radix primarily involved roasting(stir-frying), wine roasting, or raw materials. Modern mainstream processing specifications include two types of raw and honey-roasted products. In terms of quality evaluation of the medicinal materials, ancient criteria of "preferring plump and moist roots" align with modern requirement favoring "thick, robust stems with firm texture". Evaluating quality with authenticity, since the Song dynasty, it has been highly praised to produce in Chuzhou and Hengyang as the best. It was an ancient method of fixing the production area to stabilize the medicinal origin, reflecting the ancient recognition of the therapeutic efficacy of plants belonging to the genus Stemona. The main functions of Stemonae Radix remain consistent throughout history, including relieving coughs, eliminating phlegm and parasites. Based on the research results, it is recommended that when developing famous classical formulas containing the medicinal material Stemonae Radix, the botanical source specified in the 2025 edition of Chinese Pharmacopoeia should be selected. The specific species can be determined according to the distribution of resources and the main production areas, and the origin and corresponding botanical source should be fixed. Processing methods should be chosen based on the prescription requirements. It is recommended to use raw products without specified requirements.
4.Global burden of metabolic-associated fatty liver disease: A systematic analysis of Global Burden of Disease Study 2021.
Yichen WANG ; Xiaoquan HUANG ; Sitao YE ; Tian LI ; Yuting HUANG ; Mahesh CHERYALA ; Shiyao CHEN
Chinese Medical Journal 2025;138(22):2947-2954
BACKGROUND:
Metabolic-associated fatty liver disease (MAFLD) is a common liver disease and may become the leading cause of severe liver disease in the future. The Global Burden of Disease (GBD) study assesses MAFLD's impact in countries and regions worldwide, providing insights into its prevalence.
METHODS:
Prevalence data for MAFLD from 1990 to 2021 by country and region in all sex and age groups were collected from the Global Health Data Exchange. The categorization of countries and geographic areas by development was performed using the Sociodemographic Index (SDI).
RESULTS:
Between 1990 and 2021, the global crude prevalence rate of MAFLD increased from 10.6% to 16.1% (beta-coefficient: 0.2%, 95% confidence interval [CI]: 0.2-0.2%, P <0.001), and the age-standardized prevalence rate was increased from 12.1% to 15.0% (beta-coefficient: 0.1%, 95% CI: 0.1-0.1%, P <0.001). In 2021, MAFLD was estimated to have affected 1.3 billion people worldwide. Significant uptrends were observed in all regions, super regions, and SDI categories. The fastest increase from 1990 to 2021 and the highest prevalence rate in 2021 were experienced by countries and territories with high-middle and middle SDI. An increase in the prevalence of MAFLD from 1990 to 2021 was demonstrated in all but six countries.
CONCLUSIONS
In 2021, the number of patients affected by MAFLD was doubled compared to 1990, and the prevalence rate increased by over 50%. The burden of MAFLD, as measured by prevalence, was more prominent in countries and territories with middle SDI and in those located in North African and Middle Eastern, possibly due to changes in lifestyle in these areas over the past 30 years.
Humans
;
Global Burden of Disease
;
Prevalence
;
Male
;
Female
;
Middle Aged
;
Adult
;
Global Health
;
Fatty Liver/epidemiology*
;
Aged
5.Association between Y Chromosome microdeletions and tes-ticular development in male pediatric patients with congenital reproductive system abnormalities.
Yan LIANG ; Yiqing LYU ; Yichen HUANG ; Pin LI ; Wuhen XU ; Fang CHEN
Journal of Zhejiang University. Medical sciences 2025;():1-9
OBJECTIVES:
To analyze the distribution of Y chromosome azoospermia factor (AZF) microdeletions and their association with testicular development in male pediatric patients with congenital reproductive system disorders, including hypospadias, cryptorchidism, and disorders of sex development (DSD).
METHODS:
A prospective cohort study was conducted on pediatric patients admitted to the Department of Urology of Shanghai Children's Hospital from November 2021 to December 2023. The observation group included boys with hypospadias, cryptorchidism, or DSD, while the control group comprised boys with phimosis, indirect inguinal hernia, or hydrocele. Blood samples were collected for AZF microdeletion analysis using multiplex PCR to detect 15 sequence-tagged sites. Testicular ultrasound was performed to record testicular position and volume. Propensity score matching (PSM) was used to balance the groups. After matching, testicular volume differences were assessed. Stratified analyses compared testicular volume among children with AZF microdeletions, the control group, and children without micro-deletions in observation group.
RESULTS:
A total of 493 children were enrolled (observation group: 463; control group: 30). No Y chromosome microdeletions were detected in the control group. Four boys in the observation group had AZF microdeletions: one with cryptorchidism (AZFc+AZFd), one with isolated hypospadias (AZFc), and two with DSD (one with AZFb+AZFc+AZFd and one with AZFa). Ultrasonography measured 888 testicles. After PSM, testicular volume was significantly smaller in the observation group than in the control group (P<0.01). Stratified analysis revealed that among children under 9 years, those with AZF microdeletions tended to be older but had smaller testicular volumes compared to the control group and those without microdeletions in the observation group, although differences were not statistically significant (all P>0.05). Among children over 9 years, ages were comparable, but children with AZF microdeletions had smaller testicular volumes than the other two groups (statistical analysis was not performed due to small sample size).
CONCLUSIONS
The prevalence of Y chromosome microdeletions is higher in male children with congenital reproductive system disorders compared to the general population, particularly in those with DSD. Hypospadias, cryptorchidism, DSD, and AZF microdeletions may be associated with delayed testicular development in these children.
6.Metagenomics reveals an increased proportion of an Escherichia coli-dominated enterotype in elderly Chinese people.
Jinyou LI ; Yue WU ; Yichen YANG ; Lufang CHEN ; Caihong HE ; Shixian ZHOU ; Shunmei HUANG ; Xia ZHANG ; Yuming WANG ; Qifeng GUI ; Haifeng LU ; Qin ZHANG ; Yunmei YANG
Journal of Zhejiang University. Science. B 2025;26(5):477-492
Gut microbial communities are likely remodeled in tandem with accumulated physiological decline during aging, yet there is limited understanding of gut microbiome variation in advanced age. Here, we performed a metagenomics-based enterotype analysis in a geographically homogeneous cohort of 367 enrolled Chinese individuals between the ages of 60 and 94 years, with the goal of characterizing the gut microbiome of elderly individuals and identifying factors linked to enterotype variations. In addition to two adult-like enterotypes dominated by Bacteroides (ET-Bacteroides) and Prevotella (ET-Prevotella), we identified a novel enterotype dominated by Escherichia (ET-Escherichia), whose prevalence increased in advanced age. Our data demonstrated that age explained more of the variance in the gut microbiome than previously identified factors such as type 2 diabetes mellitus (T2DM) or diet. We characterized the distinct taxonomic and functional profiles of ET-Escherichia, and found the strongest cohesion and highest robustness of the microbial co-occurrence network in this enterotype, as well as the lowest species diversity. In addition, we carried out a series of correlation analyses and co-abundance network analyses, which showed that several factors were likely linked to the overabundance of Escherichia members, including advanced age, vegetable intake, and fruit intake. Overall, our data revealed an enterotype variation characterized by Escherichia enrichment in the elderly population. Considering the different age distribution of each enterotype, these findings provide new insights into the changes that occur in the gut microbiome with age and highlight the importance of microbiome-based stratification of elderly individuals.
Aged
;
Aged, 80 and over
;
Female
;
Humans
;
Male
;
Middle Aged
;
Bacteroides
;
China
;
Diabetes Mellitus, Type 2/microbiology*
;
Escherichia coli/classification*
;
Gastrointestinal Microbiome/genetics*
;
Metagenomics
;
East Asian People
7.Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract.
Rui XU ; Hengyuan YU ; Yichen WANG ; Boyu LI ; Yong CHEN ; Xuesong LIU ; Tengfei XU
Journal of Pharmaceutical Analysis 2025;15(2):101101-101101
Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.
8.Effect of Bushen Huoxue Prescription in Regulating PINK1/Parkin Pathway in Rat Model of Premature Ovarian Failure
Kailing WANG ; Yichen JING ; Guiyun WANG ; Yueheng LI ; Huiping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):150-158
ObjectiveTo investigate the mechanism of action of Bushen Huoxue prescription (BSHXP) in regulating premature ovarian failure in rats through the PTEN-induced kinase 1 (PINK1)/Parkinson's protein (Parkin) signaling pathway-mediated mitophagy. MethodsA total of 48 rats were randomly divided into a blank group consisting of eight rats, while the remaining 40 rats underwent modeling. The modeling group was intraperitoneally injected with 4 mg·kg-1 cisplatin solution, followed by a second injection one week later, for a total of two injections. The estrous cycle was observed through vaginal smears for 14 consecutive days to determine whether the modeling was successful. The successfully modeled rats were randomly divided into a model group, groups receiving low, medium, and high doses of BSHXP at 9.72, 19.44, and 38.88 g·kg-1·d-1 (BSHXP-L, BSHXP-M, and BSHXP-H groups), and a positive control group treated with estradiol valerate (0.09 mg·kg-1·d-1), for 21 consecutive days. The body weight of the rats was measured weekly. After the final administration, rats were anesthetized, and their blood and ovaries were collected. The ovarian weight was measured. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2). Assay kits were used to measure the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the rat serum. Hematoxylin-eosin (HE) staining was used to observe the morphological changes in the ovaries. Immunohistochemistry (IHC) was performed to detect microtubule autophagy-related protein 1 light chain 3B(LC3B) protein expression in ovarian tissue, and electron microscopy was employed to examine the mitochondrial and autophagosome changes in the rat ovaries. Western blot was used to detect the protein expression of PINK1, Parkin, LC3B, and p62. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of PINK1, Parkin, LC3B, and p62 in ovarian tissue. ResultsCompared with the blank group, the model group showed significant reductions in body weight, weight gain, and ovarian weight (P<0.01), along with decreased serum AMH and E2 levels (P<0.01), while FSH and LH levels were increased (P<0.01). Serum MDA levels were significantly increased (P<0.01), and SOD levels were significantly reduced (P<0.01). The ovarian tissue structure was disordered, and the zona pellucida was wrinkled into an irregular acidophilic annular object, accompanied by an increased number of closed follicles. Electron microscopy showed mitochondrial swelling, unclear structure, and no obvious autophagosomes and autolysosome structures. The proteins and mRNA expression levels of PINK1, Parkin, LC3B, and p62 in the ovarian tissue were significantly reduced (P<0.01). Compared with the model group, all treatment groups showed varying degrees of increases in body weight and ovarian weight (P<0.05, P<0.01). Except for the BSHXP-L group, all treatment groups showed increased body weight gain (P<0.01). All treatment groups showed significantly increased serum AMH and decreased FSH levels (P<0.01). Except for the BSHXP group, all treatment groups showed varying degrees of increase and decrease in serum E2 and LH levels (P<0.05, P<0.01). All treatment groups showed reduced serum MDA levels (P<0.01), while the BSHXP-M, BSHXP-H, and the positive control groups demonstrated improved serum SOD levels (P<0.05, P<0.01). All treatment groups showed an increased number of follicles at all stages, visible mature follicles, and a decreased number of closed follicles. Electron microscopy showed relieved mitochondrial swelling, morphology close to normal, clear structure, and visible formation of autolysosomes in all treatment groups. Additionally, the protein and mRNA expression levels of PINK1, Parkin, LC3B, and p62 in ovarian tissue were significantly increased (P<0.05, P<0.01). ConclusionBSHXP may improve ovarian function in rats with premature ovarian failure by regulating the PINK1/Parkin signaling pathway, activating mitochondrial autophagy, and reducing oxidative damage.
9.Effect of Bushen Huoxue Prescription in Regulating PINK1/Parkin Pathway in Rat Model of Premature Ovarian Failure
Kailing WANG ; Yichen JING ; Guiyun WANG ; Yueheng LI ; Huiping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):150-158
ObjectiveTo investigate the mechanism of action of Bushen Huoxue prescription (BSHXP) in regulating premature ovarian failure in rats through the PTEN-induced kinase 1 (PINK1)/Parkinson's protein (Parkin) signaling pathway-mediated mitophagy. MethodsA total of 48 rats were randomly divided into a blank group consisting of eight rats, while the remaining 40 rats underwent modeling. The modeling group was intraperitoneally injected with 4 mg·kg-1 cisplatin solution, followed by a second injection one week later, for a total of two injections. The estrous cycle was observed through vaginal smears for 14 consecutive days to determine whether the modeling was successful. The successfully modeled rats were randomly divided into a model group, groups receiving low, medium, and high doses of BSHXP at 9.72, 19.44, and 38.88 g·kg-1·d-1 (BSHXP-L, BSHXP-M, and BSHXP-H groups), and a positive control group treated with estradiol valerate (0.09 mg·kg-1·d-1), for 21 consecutive days. The body weight of the rats was measured weekly. After the final administration, rats were anesthetized, and their blood and ovaries were collected. The ovarian weight was measured. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2). Assay kits were used to measure the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the rat serum. Hematoxylin-eosin (HE) staining was used to observe the morphological changes in the ovaries. Immunohistochemistry (IHC) was performed to detect microtubule autophagy-related protein 1 light chain 3B(LC3B) protein expression in ovarian tissue, and electron microscopy was employed to examine the mitochondrial and autophagosome changes in the rat ovaries. Western blot was used to detect the protein expression of PINK1, Parkin, LC3B, and p62. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of PINK1, Parkin, LC3B, and p62 in ovarian tissue. ResultsCompared with the blank group, the model group showed significant reductions in body weight, weight gain, and ovarian weight (P<0.01), along with decreased serum AMH and E2 levels (P<0.01), while FSH and LH levels were increased (P<0.01). Serum MDA levels were significantly increased (P<0.01), and SOD levels were significantly reduced (P<0.01). The ovarian tissue structure was disordered, and the zona pellucida was wrinkled into an irregular acidophilic annular object, accompanied by an increased number of closed follicles. Electron microscopy showed mitochondrial swelling, unclear structure, and no obvious autophagosomes and autolysosome structures. The proteins and mRNA expression levels of PINK1, Parkin, LC3B, and p62 in the ovarian tissue were significantly reduced (P<0.01). Compared with the model group, all treatment groups showed varying degrees of increases in body weight and ovarian weight (P<0.05, P<0.01). Except for the BSHXP-L group, all treatment groups showed increased body weight gain (P<0.01). All treatment groups showed significantly increased serum AMH and decreased FSH levels (P<0.01). Except for the BSHXP group, all treatment groups showed varying degrees of increase and decrease in serum E2 and LH levels (P<0.05, P<0.01). All treatment groups showed reduced serum MDA levels (P<0.01), while the BSHXP-M, BSHXP-H, and the positive control groups demonstrated improved serum SOD levels (P<0.05, P<0.01). All treatment groups showed an increased number of follicles at all stages, visible mature follicles, and a decreased number of closed follicles. Electron microscopy showed relieved mitochondrial swelling, morphology close to normal, clear structure, and visible formation of autolysosomes in all treatment groups. Additionally, the protein and mRNA expression levels of PINK1, Parkin, LC3B, and p62 in ovarian tissue were significantly increased (P<0.05, P<0.01). ConclusionBSHXP may improve ovarian function in rats with premature ovarian failure by regulating the PINK1/Parkin signaling pathway, activating mitochondrial autophagy, and reducing oxidative damage.
10.Identification of potential therapeutic targets for hair color and hair shaft abnormalities by integrating human plasma proteomics
Guangdi LI ; Guiwen ZHOU ; Yichen WANG ; Xiao XU ; Minliang CHEN
Chinese Journal of Plastic Surgery 2025;41(7):734-743
Objective:To identify potential therapeutic targets for the treatment of hair color and hair shaft abnormalities, thereby offering innovative insights and strategies for the management of the associated conditions.Methods:Using the protein quantitative trait locus(pQTL) data derived from extensive proteomics studies, a two-sample Mendelian randomization was conducted to preliminarily identify potential drug therapeutic targets. Following this, sensitivity analyses were performed to evaluate potential confounding factors, including heterogeneity and horizontal pleiotropy. A leave-one-out sensitivity analysis was also conducted, systematically excluding each single nucleotide polymorphism (SNP) to evaluate their individual impact. Additionally, co-localization analysis was carried out to determine the presence of shared genetic variants between the identified plasma proteins and the relevant traits.Results:The proteomic data analyzed in this investigation encompassed 4 907 pQTLs, while the genetic data pertaining to hair pigmentation and shaft abnormalities included 124 cases and 432 686 controls. Through the Mendelian randomization screening, six candidate protein genes were identified: HLA-DQA2, CTSB, KIR2DS2, SVEP1, HOMER2, and HOMER1. Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy among these proteins. The leave-one-out sensitivity analysis demonstrated that no single SNP significantly affected the overall findings. Notably, HOMER2 was substantiated by co-localization analysis, which provided robust evidence of its potential role in regulating the genetic mechanisms associated with hair pigmentation and shaft integrity.Conclusion:This study successfully identified six potential therapeutic targets for hair pigmentation and shaft abnormalities, with HOMER2 exhibiting the most compelling evidence. These findings pave the way for novel therapeutic approaches in the treatment of hair color and hair shaft disorders.

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