This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

ObjectiveTo characterize the changes of metabolites of Blumea balsamifera in the process of sweating by non-targeted metabolomics， and to investigate the influence of sweating processing on the constituents of B. balsamifera. MethodsUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS） metabolomics was used to identify the metabolites in no sweating group（F1）， sweating 2 d group（F2） and sweating 4 d group（F3）， the differences of metabolites between the groups were compared by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， and differential metabolites were screened according to the variable importance in the projection（VIP） value>1 and P<0.05， and the pathway enrichment of the differential metabolites was analyzed by Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultsThe results of PCA and OPLS-DA showed a clear distinction between the three groups of samples， indicating significant differences in the compositions of the three groups of samples. A total of 433 differential metabolites were screened between the F1 and F2， with 154 up-regulated and 279 down-regulated， the significant up-regulated metabolites were tangeritin， 5-O-demethylnobiletin and so on， while the metabolites with significant down-regulation included alternariol， fortunellin， etc. A total of 379 differential metabolites were screened between the F2 and F3， with 150 up-regulated and 229 down-regulated， the significant up-regulated metabolites were isoimperatorin， helianyl octanoate and so on， and the significant down-regulated metabolites were hovenoside I， goyasaponin Ⅲ， etc. KEGG pathway enrichment analysis showed that tyrosine metabolism， isoquinoline alkaloid biosynthesis， phenylalanine， tyrosine and tryptophan biosynthesis， tryptophan metabolism， valine， leucine and isoleucine biosynthesis， pantothenate and coenzyme A biosynthesis may be the key pathways affecting metabolite differences of B. balsamifera after sweating treatment. ConclusionSweating can reduce the content of endophytic mycotoxins in B. balsamifera and has a great impact on the synthesis and metabolic pathways of total flavonoids and auxin. This study can provide a reference for the process research on the sweating conditions of B. balsamifera.

ObjectiveTo establish a rapid analytical method for identifying the differential components in Poria cocos medicinal materials based on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， combined with mass defect filtering（MDF） and molecular network integration techniques. MethodsUPLC-Q-Orbitrap-MS was used for MS data acquisition and identification of P. cocos medicinal materials， with the help of MDF for the study of cleavage behavior and structural identification of triterpenoids. According to the similarity of MS/MS fragmentation patterns of each component， global natural product social molecular network（GNPS） was established， and Cytoscape 3.6.1 was used to screen molecular clusters with similar structures and the the structure of main compound classes were identified and confirmed. Multivariate statistical analyses such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to screen the differential components of the five P. cocos medicinal materials with the variable importance in the projection（VIP） value>1 and P<0.05 as the criteria. ResultsA total of 66 compounds were identified by database comparison， 8 compounds were newly identified by MDF， 28 compounds were newly identified by GNPS， and a total of 102 chemical compounds were identified， including 43 triterpenoids， 16 saccharides， 26 amino acids and peptides， 3 nucleosides， and 14 other compounds. Triterpenoids were predominant in Poriae Cutis and wild Fushen， amino acids and peptides were the most abundant in Poria and cultivated Fushen， carbohydrates were the most abundant in Poriae Cutis. Type Ⅰ and Ⅱ triterpenoids had higher amounts in Poria and cultivated Fushen， type Ⅲ triterpenoids were more abundant in Poriae Cutis， all four types of triterpenoids were higher in Fushenmu， and type Ⅰ， Ⅱ， and Ⅳ triterpenoids were higher in wild Fushen. A total of 12 common differential chemical constituents were screened， including serine， guanosine， gallic acid， 2-octenal， maltotriose， trametenolic acid， dehydroeburicoic acid， dehydrotrametenolic acid， poricoic acid A， poricoic acid B， poricoic acid E and G， but the relative contents of them varied significantly among different medicinal materials. ConclusionAmong the five P. cocos medicinal materials， the types of constituents are generally similar， but their relative contents differed significantly among these medicinal materials， especially in the distribution of triterpenoids. The integration of UPLC-Q-Orbitrap-MS， MDF and GNPS can provide a reference for the rapid qualitative analysis of other Chinese medicines.

ObjectiveTo establish a rapid analytical method for identifying the differential components in Poria cocos medicinal materials based on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， combined with mass defect filtering（MDF） and molecular network integration techniques. MethodsUPLC-Q-Orbitrap-MS was used for MS data acquisition and identification of P. cocos medicinal materials， with the help of MDF for the study of cleavage behavior and structural identification of triterpenoids. According to the similarity of MS/MS fragmentation patterns of each component， global natural product social molecular network（GNPS） was established， and Cytoscape 3.6.1 was used to screen molecular clusters with similar structures and the the structure of main compound classes were identified and confirmed. Multivariate statistical analyses such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to screen the differential components of the five P. cocos medicinal materials with the variable importance in the projection（VIP） value>1 and P<0.05 as the criteria. ResultsA total of 66 compounds were identified by database comparison， 8 compounds were newly identified by MDF， 28 compounds were newly identified by GNPS， and a total of 102 chemical compounds were identified， including 43 triterpenoids， 16 saccharides， 26 amino acids and peptides， 3 nucleosides， and 14 other compounds. Triterpenoids were predominant in Poriae Cutis and wild Fushen， amino acids and peptides were the most abundant in Poria and cultivated Fushen， carbohydrates were the most abundant in Poriae Cutis. Type Ⅰ and Ⅱ triterpenoids had higher amounts in Poria and cultivated Fushen， type Ⅲ triterpenoids were more abundant in Poriae Cutis， all four types of triterpenoids were higher in Fushenmu， and type Ⅰ， Ⅱ， and Ⅳ triterpenoids were higher in wild Fushen. A total of 12 common differential chemical constituents were screened， including serine， guanosine， gallic acid， 2-octenal， maltotriose， trametenolic acid， dehydroeburicoic acid， dehydrotrametenolic acid， poricoic acid A， poricoic acid B， poricoic acid E and G， but the relative contents of them varied significantly among different medicinal materials. ConclusionAmong the five P. cocos medicinal materials， the types of constituents are generally similar， but their relative contents differed significantly among these medicinal materials， especially in the distribution of triterpenoids. The integration of UPLC-Q-Orbitrap-MS， MDF and GNPS can provide a reference for the rapid qualitative analysis of other Chinese medicines.

To establish a rapid Akabane virus(AKAV)antibody detection method in animals,the re-combination AKAV N protein was expressed by the expression system of Escherichia coli,puri-fied from the supernatant,and used to immunized New Zealand White rabbits.The polyclonal anti-body against AKAV N protein had a titer of 1∶8.192×107 and showed good reactivity.After opti-mizing the reaction conditions,an AKAV double antigen sandwich ELISA antibody detection method was established.This method can detect AKAV antibody in a variety of animals including cattles,sheep and goats.The method had no cross-reactivity with the positive serum of BTV,EHDV,BEV and PRV with the intra-and inter-batch coefficients of variation less than 10％.Com-pared with the AKAV blocking ELISA kit,the sensibility of the method was increased by 8-16 folds with a compliance rate of 93.33％and the κ value of 0.864.These results showed that the double antigen sandwich ELISA displayed strong specificity,high sensitivity and repeatability,which could provide technical suport for detection,the prevention and control of AKAV.

To establish a rapid Akabane virus(AKAV)antibody detection method in animals,the re-combination AKAV N protein was expressed by the expression system of Escherichia coli,puri-fied from the supernatant,and used to immunized New Zealand White rabbits.The polyclonal anti-body against AKAV N protein had a titer of 1∶8.192×107 and showed good reactivity.After opti-mizing the reaction conditions,an AKAV double antigen sandwich ELISA antibody detection method was established.This method can detect AKAV antibody in a variety of animals including cattles,sheep and goats.The method had no cross-reactivity with the positive serum of BTV,EHDV,BEV and PRV with the intra-and inter-batch coefficients of variation less than 10％.Com-pared with the AKAV blocking ELISA kit,the sensibility of the method was increased by 8-16 folds with a compliance rate of 93.33％and the κ value of 0.864.These results showed that the double antigen sandwich ELISA displayed strong specificity,high sensitivity and repeatability,which could provide technical suport for detection,the prevention and control of AKAV.

OBJECTIVE: This study aimed to explore the association between humidity exposure and the risk of cardiovascular disease (CVD), utilizing follow-up data and relative humidity (RH) metric assessments. METHODS: We extracted the baseline data from the China Hypertension Survey (CHS) of 24,510 enrolled participants aged ≥ 35 years without a history of CVD between 2012 and 2015 and followed them up from 2018 to 2019. The National Meteorological Information Center (NMIC) of the China Meteorological Administration (CMA) provided the quality-controlled relative humidity (RH) datasets. Cox proportional hazards models were used to estimate hazard ratios ( HRs) for CVD in relation to RH. RESULTS: During the follow-up period (2018-2019), 973 patients with CVD were identified. The HR of CVD risk was 1.17 (95% CI: 1.04-1.31) per 10% increase in summer mean RH. Compared with participants in the 3 ^rd quintile group, those in the 1 ^st and 5 ^th quintiles of RH had a higher risk of CVD. For summer mean RH, the HRs (95% CIs) for the 1 ^st and 5 ^th quintiles were 1.34 (1.04-1.71) and 1.44 (1.14-1.83), respectively. The relationship ("U" shape) between summer mean RH and the risk of CVD was nonlinear. Stratified analyses indicated that the risk of CVD was substantially influenced by the summer mean RH in female, older individuals, and those in southern China. CONCLUSION Unsuitable (too high or low) humidity environments affect the risk of CVD. Our study highlights those future policies for adapting to climate change should consider the humidity-CVD relationship.
Humans ; Humidity/adverse effects* ; Cardiovascular Diseases/etiology* ; Female ; Male ; Middle Aged ; Prospective Studies ; China/epidemiology* ; Adult ; Aged ; Risk Factors ; Proportional Hazards Models ; Seasons

OBJECTIVETo explore the relationship between the time after thrombosis and the efficacy of combined ultrasound and microbubble treatment for rescuing the ischemic tissues.

METHODSRat models of thrombosis in the right common iliac artery were established and received combined ultrasound and microbubble treatment at 3, 6 and 12 h after thrombosis. The recanalization rate of the right common iliac artery was assessed using both 2-dimensional and Doppler ultrasound. The plateau acoustic intensity (AI) was quantified for estimating the skeletal microvascular blood volume, and skeletal muscle injury markers including myoglobin (Mb) and creatinine kinase (CK) were measured using ELISA. Postmortem TUNEL staining was used to detect the apoptotic rate of skeletal muscle cells in the hind limb of the rats.

RESULTSCompared with those in 3 h group, the recanalization rate and AI were significantly lower, and the levels of Mb and CK and the apoptotic rate of the skeletal muscle cells were significantly higher in both 6 h group and 12 h group ( < 0.05). Compared with those in 6 h group, the rats receiving treatment at 12 h after thrombosis showed significantly lowered AI and increased Mb, CK and apoptotic rate of the skeletal muscle cells ( < 0.05).

CONCLUSIONSThe efficacy of combined ultrasound and microbubble treatment for rescuing ischemic tissues tends to be attenuated as the time after thrombosis prolongs in rats.

Objective To explore the physiological characteristics of vascular invasion of hepatic alveolar echinococcosis(HAE) and the growth pattern of lesion.Methods 120 cases with HAE were all scanned by 256 slices MSCT,then the images were taken three-dimensional reconstruction.A comparison between pathology and images were made for the evaluation of vascular invasion.Results Pathological examination showed that the invasion rate of intrahepatic vein(left hepatic vein,middle hepatic vein,right hepatic vein, inferior vena cava),portal vein and hepatic artery were 34.38%,31.11%,22.50%,respectively.176 branches of the intrahepatic vein, 67 branches of the hepatic artery and 127 branches of portal vein were involved.Combined with the pathology,the Kappa values were 0.868,0.725 and 0.844.Conclusion HAE is easy to involve the intrahepatic veins as it grows,considering its"indulgence of vein"feature.In order to improve the targeting effect,the mode of administration could be changed.MSCT can exactly evaluate the invasion of intrahepatic vessels,providing important basis for clinical treatment.

Aim To evaluate the mucosal-protective effects of carboxymethylpachyman( CMP) on Fluorou-racil(5-Fu)-induced mice intestinal mucositis and ex-plore its mechanisms. Methods ICR mice were as-signed randomly to four groups:normal group( n=8;re-ceiving pure water orally for 14 d) ,CMP group( n=8;200 mg·kg-1 CMP for 14 d orally),5-Fu group(n=8;25 mg·kg-1 5-Fu for 7 d,intraperitoneally( i. p. ) , and CMP+5-Fu group( n=8;200 mg·kg-1 CMP for 14 d orally and 25 mg·kg-1 5-Fu for 7 d,i. p. ). At day 14the mice were sacrificed. The intestinal propel-ling rate and the colon length were measured. ROS, GSH and IL-1βcontents,and CAT,GSH-Px activities in homogenate supernatant of PPs were measured by kits for observing the effects of CMP on mice lipid peroxida-tion and intestinal mucosal inflammatory induced by 5-Fu. Colon tissues were used for hematoxylin and eosin ( HE ) staining for the determination of the effect of CMP on mice colon histopathology, immunohistochem-istry for the protein levels of NF-κB and p-p38 . Results CMP significantly extended colon lengths,accelerate the intestinal propelling rates, reduced colonic mucosa epithelium goblet cell loss, inflammatory cells infiltra-tion,and crypt depth shallow induced by 5-Fu. CMP obviously reduced ROS and IL-1β contents, and pre-vented reductions in homogenate supernatant of PPs GSH content, CATand GSH-Px activities by 5-Fu ad-ministration,and also reduced the expression of NF-κB and p-p38 in colon tissues. However, CMP alone had no effect on the colon of normal mice. Conclusion The current study demonstrates that CMP may have sig-nificant protective effects against 5-Fu-induced intesti-nal mucositis. Its mechanism may be related to enhan-cing the antioxidant activity,anti-inflammatory and an-ti-apoptotic effects.