Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

ObjectiveThis study aims to explore the mechanism and targets of Shenfu Injection in regulating glycolysis to intervene in myocardial fibrosis in chronic heart failure based on the hypoxia-inducible factor-1α （HIF-1α）/ 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3） signaling pathway. MethodsA rat model of chronic heart failure was established by subcutaneous injection of isoproterenol （ISO）. After successful modeling， the rats were randomly divided into the Sham group， Model group， Shenfu injection （SFI， 6 mL·kg^-1） group， and inhibitor （3PO， 35 mg·kg^-1） group， according to a random number table， and they were treated for 15 days. Cardiac function was evaluated by echocardiography， and serum N-terminal pro-brain natriuretic peptide （NT-proBNP） levels were detected by enzyme-linked immunosorbent assay （ELISA）. Fasting body weight and heart weight were measured， and the heart index （HI） was calculated. Pathological changes in myocardial tissue were observed by hematoxylin-eosin （HE） and Masson staining， and the fibrosis rate was calculated. Biochemical assays were used to determine serum levels of glucose （GLU）， lactic acid （LA）， and pyruvic acid （PA）. Western blot was used to analyze the expression of proteins related to the HIF-1α/PFKFB3 signaling pathway （HIF-1α and PFKFB3）， glycolysis-related proteins （HK1， HK2， PKM2， and LDHA）， and fibrosis-related proteins ［transforming growth factor （TGF）-β₁， α-smooth muscle actin （α-SMA）， and Collagen type Ⅰ α1 （ColⅠA1）］. Real-time PCR was used to detect the mRNA expression of HIF-1α and PFKFB3 in myocardial tissue. ResultsCompared with the Sham group， the Model group showed significantly decreased left ventricular ejection fraction （LVEF）， left ventricular shortening fraction （LVFS）， interventricular septal thickness （IVSd）， and interventricular septal strain （IVSs） （P<0.05）， while left ventricular internal dimension at end-diastole （LVDd） and end-systole （LVIDs） were increased （P<0.05）. Serum NT-proBNP levels were significantly increased （P<0.01）， and body weight was decreased. Heart weight was increased， and the HIT index was increased （P<0.05）. Myocardial tissue exhibited inflammatory cell infiltration and collagen fiber deposition， and the fibrosis rate was significantly increased （P<0.05）. Serum GLU was decreased （P<0.05）， while LA and PA levels were increased （P<0.05）. Protein expressions of HIF-1α， PFKFB3， HK1， HK2， PKM2， LDHA， TGF-β₁， α-SMA， and ColⅠA1， as well as the mRNA expression of HIF-1α and PFKFB3 were increased （P<0.05）. Compared with the Model group， both the SFI group and 3PO groups showed significant improvements in LVEF， LVFS， IVSd， and IVSs （P<0.05） and decreases in LVDd， LVIDs， and NT-proBNP levels （P<0.05）. Body weight was significantly increased. Heart weight was significantly decreased， and the HIT index was significantly decreased （P<0.05）. Inflammatory cell infiltration， collagen fiber deposition， and the fibrosis rate were significantly decreased （P<0.05）. Serum GLU levels were significantly increased （P<0.05）， while LA and PA levels were decreased （P<0.05）. Expressions of glycolysis-related proteins， fibrosis-related proteins， and HIF-1α/PFKFB3 pathway-related proteins and mRNAs were significantly suppressed （P<0.05）. ConclusionSFI improves cardiac function in chronic heart failure by downregulating the expression of HIF-1α/PFKFB3 signaling pathway-related proteins， regulating glycolysis， and inhibiting myocardial fibrosis.

OBJECTIVE To analyze the components migrating to blood and metabolites of Polygonum cuspidatum in rats with acute gouty arthritis （AGA）. METHODS SD rats were randomly divided into blank group， model group and P. cuspidatum group （10 g/kg， by raw material）， with 6 rats in each group. Except for blank group， AGA model was induced in the remaining groups by injecting potassium oxonate and sodium urate； meanwhile， they were administered corresponding drug solutions or water intragastrically， once a day， for 10 consecutive days. The histopathological morphology of the knee joint tissues in rats was observed；rat serum samples were collected， and the components migrating to blood and metabolites of P. cuspidatum were analyzed by using UPLC-Q-Exactive-Orbitrap-MS. RESULTS Following the intervention with P. cuspidatum， the histopathological morphology of the knee joint synovial tissue in AGA rats showed significant improvement， with reduced inflammatory cell infiltration and hyperplasia， and the preservation of the honeycomb-like structure integrity. In both positive and negative ion modes， a total of 67 chemical components were detected in the serum of rats from P. cuspidatum group， including 25 prototype components and 42 metabolites. The involved compound types encompassed stilbenes， anthraquinones， naphthols， and flavonoids， among others. The metabolic reactions identified included methylation， acetylation， sulfation， and glucuronidation. Notably， compounds such as polydatin， resveratrol and emodin were capable of entering the bloodstream in their prototype forms and undergoing in vivo metabolism. CONCLUSIONS Compounds such as polydatin， resveratrol and emodin are likely to be the active components responsible for the anti-AGA effects of P. cuspidatum.

The Compilation Instructions for Expert Consensus on Clinical Application of Dieda Huoxue capsules systematically expound the development methods and evidence-based basis of this consensus. In view of the weak clinical application evidence and ambiguous indications of Dieda Huoxue capsules， the Institute of Basic Research in Clinical Medicine of the China Academy of Chinese Medical Sciences and Wangjing Hospital took the lead and collaborated with 33 experts from 28 medical institutions nationwide. They strictly followed the World Health Organization （WHO） guideline-making norms and the Grading of Recommendations Assessment， Development and Evaluations （GRADE） evidence-grading system and completed the compilation through multidisciplinary cooperation. The workflow included constructing clinical questions （19 items were screened by the nominal group technique）， retrieving evidence （from Chinese and English databases and grey literature）， assessing safety （integrating drug monitoring data and clinical investigations）， and forming recommendations and consensus suggestions （3 recommendations were reached via the GRADE grid method， and 16 consensus suggestions were reached by the majority vote rule）. The results indicate that the consensus clearly states that this medicine （Dieda Huoxue capsules） is applicable to conditions like traumatic injury， blood stasis-induced pain， and sudden lumbar sprains. The recommended dose is 6 capsules each time， twice a day. Combining oral administration with external application can enhance the efficacy， and elderly patients should take the medicine at intervals. Safety monitoring suggests that it should be used with caution in people with a bleeding tendency and those with an allergic constitution. The compilation process involved three rounds of reviews by internal and external experts. Literature analysis， the Delphi method， and clinical applicability tests were employed to ensure methodological rigor. The compilation instructions comprehensively present key aspects such as project approval and registration， conflict-of-interest statements， and evidence evaluation through 12 appendices， providing methodological support for the clinical translation of the consensus. In the future， it will be continuously improved through a dynamic revision mechanism.

A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) represent a diverse family of secreted metalloproteinases, comprising 19 distinct members categorized into five groups based on their substrate specificity: proteoglycanases, procollagen N-peptidases, von Willebrand factor-cleaving protease, cartilage oligomeric matrix proteases and other proteases. Among these, ADAMTS proteoglycanases predominantly target hyalectans, pivotal components in extracellular matrix (ECM) remodeling and inflammation. Dysfunction of ADAMTS proteoglycanases disrupts the structure and function of hyalectans, thereby perturbing ECM homeostasis, resulting in reproduction disorders, including abnormal follicular development, ovulation dysfunction, impaired implantation, placentation and preterm labor. Hence, investigation of the role of ADAMTS proteoglycanases offers valuable insights into the molecular mechanisms underlying the physiological or pathological processes within the female reproductive system, thereby paving the way for innovative strategies in predicting, preventing and treating reproductive system diseases. This review summarizes the recent research advances in the structure and regulation of ADAMTS proteoglycanases and their role in female reproductive system.
Humans ; Female ; ADAMTS Proteins/physiology* ; ADAM Proteins/physiology* ; Pregnancy ; Animals ; Genitalia, Female/enzymology* ; Extracellular Matrix/metabolism*

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

OBJECTIVE: To evaluate the early effectiveness of navigation-free robot-assisted total knee arthroplasty (TKA) compared to traditional TKA in the treatment of knee osteoarthritis combined with extra-articular deformities. METHODS: The clinical data of 30 patients with knee osteoarthritis combined with extra-articular deformities who met the selection criteria between June 2019 and January 2024 were retrospectively analyzed. Fifteen patients underwent CORI navigation-free robot-assisted TKA and intra-articular osteotomy (robot group) and 15 patients underwent traditional TKA and intra-articular osteotomy (traditional group). There was no significant difference in age, gender, body mass index, affected knee side, extra-articular deformity angle, deformity position, deformity type, and preoperative knee range of motion, American Knee Society (KSS) knee score and KSS function score, and lower limb alignment deviation between the two groups ( P>0.05). The operation time, intraoperative blood loss, and complications of the two groups were recorded and compared. The knee range of motion and lower limb alignment deviation were recorded before operation and at 6 months after operation, and the knee joint function was evaluated by KSS knee score and function score. RESULTS: There was no significant difference in operation time between the two groups ( P>0.05); the intraoperative blood loss in the robot group was significantly less than that in the traditional group ( P<0.05). Patients in both groups were followed up 6-12 months, with an average of 8.7 months. The incisions of all patients healed well, and there was no postoperative complication such as thrombosis or infection. At 6 months after operation, X-ray examination showed that the position of the prosthesis was good in both groups, and there was no loosening or dislocation of the prosthesis. The knee joint range of motion, the lower limb alignment deviation, and the KSS knee score and KSS function score significantly improved in both groups ( P<0.05) compared to preoperative ones. The changes of lower limb alignment deviation and KSS function score between pre- and post-operation in the robot group were significantly better than those in the traditional group ( P<0.05), while the changes of other indicators between pre- and post-operation in the two groups were not significant ( P>0.05). CONCLUSION Compared to traditional TKA, navigation-free robot-assisted TKA for knee osteoarthritis with extra-articular deformities results in less intraoperative blood loss, more precise reconstruction of lower limb alignment, and better early effectiveness. However, long-term effectiveness require further investigation.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Robotic Surgical Procedures/methods* ; Male ; Female ; Retrospective Studies ; Range of Motion, Articular ; Middle Aged ; Aged ; Treatment Outcome ; Osteotomy/methods* ; Knee Joint/physiopathology* ; Operative Time