OBJECTIVE: To investigate the molecular mechanism for a family with Hereditary coagulation factor Ⅻ (FⅫ) deficiency. METHODS: The proband, a 63-year-old female, was admitted to the First Affiliated Hospital of Wenzhou Medical University in August 2024 for lumbar disc herniation. Coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (APTT), and FⅫ activity (FⅫ:C), were carried out for the proband and her family members (9 individuals from three generations) using a one-stage clotting assay. The level of FⅫ antigen (FⅫ:Ag) was determined with an Enzyme-linked immunosorbent assay (ELISA). Sanger sequencing was conducted to identify potential variants in the F12 gene. Multiple in silico tools were used to predict the conservation, hydrophobicity, and structural impact of the identified variants. Recombinant expression plasmids were constructed and transiently transfected into HEK293T cells. The recombinant FⅫ protein was analyzed using Western blotting (WB) and ELISA. This study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (Ethics No.: KY2022-R193). RESULTS: The proband showed a markedly prolonged APTT (160.3 s) and significantly decreased FⅫ:C (2%) and FⅫ:Ag (5%) levels. Analysis of the F12 gene sequence revealed a 46C/T genotype in the promoter region, a heterozygous c.1457G>A (p.Cys467Tyr) missense variant in exon 12, and a heterozygous c.1561G>A (p.Glu502Lys) missense variant in exon 13. Bioinformatic analysis showed that the p.Cys467 is highly conserved across various species, and the p.Cys467Tyr variant may affect local structural stability of the FⅫ protein. The p.Cys467Tyr variant had no effect on the transcription of the F12 gene. However, the variant has significantly decreased the FⅫ:Ag levels and FⅫ protein expression in the cell culture supernatant compared to the wild-type expression vector, while in the cell lysate, it is higher than the wild-type expression vector. In other words, the p.Cys467Tyr variant has probably caused a secretion defect of FⅫ protein. CONCLUSION The 46C/T genotype, the heterozygous p.Cys467Tyr missense variant, and the heterozygous p.Glu502Lys missense variant are associated with reduced plasma FⅫ levels in this pedigree. The p.Cys467Tyr variant, which was unreported previously, did not affect the synthesis of FⅫ but may have resulted in a secretion defect.
Humans ; Female ; Middle Aged ; Mutation, Missense ; Pedigree ; HEK293 Cells ; Male ; Factor XII/genetics* ; Adult ; Factor XII Deficiency/genetics*

Two novel skeleton sesquiterpenoids (1 and 6), along with four new iphionane-type sesquiterpenes (2-5) and six new cyperane-type sesquiterpenes (7-11), were isolated from the whole plant of Artemisia hedinii (A. hedinii). The two novel skeleton compounds (1 and 6) were derived from the decarbonization of iphionane and cyperane-type sesquiterpenes, respectively. Their structures were elucidated through a comprehensive analysis of spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) spectra. The absolute configurations were determined using electronic circular dichroism (ECD) spectra, single-crystal X-ray crystallographic analyses, time-dependent density functional theory (TDDFT) ECD calculation, density functional theory (DFT) NMR calculations, and biomimetic syntheses. The biomimetic syntheses of the two novel skeletons (1 and 6) were inspired by potential biogenetic pathways, utilizing a predominant eudesmane-type sesquiterpene (A) in A. hedinii as the substrate. All compounds were evaluated in LX-2 cells for their anti-hepatic fibrosis activity. Compounds 2, 8, and 10 exhibited significant activity in downregulating the expression of α-smooth muscle actin (α-SMA), a protein involved in hepatic fibrosis.
Artemisia/chemistry* ; Sesquiterpenes/chemical synthesis* ; Molecular Structure ; Humans ; Liver Cirrhosis/genetics* ; Biomimetics ; Plant Extracts/pharmacology*

Objective:This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma.Methods:The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) .Results:Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration ( P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum β-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups ( P>0.05), and the median PFS and OS time were not reached ( P>0.05) . Conclusions:In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.

Objective:To explore the medication rules of Professor Wang Pei in the treatment of colon cancer.Methods:The medical records of Professor Wang Pei's outpatient treatment for colon cancer were collected, entered into the Traditional Chinese Medicine Inheritance Computing Platform V3.0, and the laws of the prescription's nature, flavor, meridian, drug frequency, drug combination, association rules, and cluster analysis were explored.Results:A total of 65 prescriptions were collected, including 150 Chinese materia medica. The medicinal properties of these Chinese materia medica are mainly warm, cold and flat, the tastes were mainly sweet, bitter and pungent, and the meridians were mainly liver, spleen and kidney meridians. Dampness category and blood circulation promoting and blood stasis category were mainly used, and the most frequently used drugs include Poria, Polyporus, Scutellariae Barbatae Herba, Astragali Radix, Curcumae Rhizoma, and the pairs of Polyporus- Poria, Astragali Radix- Astragali Radix Praeparata cum Melle, Scutellariae Barbatae Herba- Curcumae Rhizoma. Twenty nine high-related drug pairs were obtained from association rules, including Polyporus- Astragali Radix Praeparata cum Melle- Astragali Radix, Poria- Scutellariae Barbatae Herba- Polyporus, Scutellariae Barbatae Herba- Curcumae Rhizoma- Polyporus. The cluster analysis showed the combination of 6 types of medicines mainly focuses on strengthening the spleen and removing dampness, nourishing qi and promoting blood, clearing heat and detoxifying, and astringing the intestines to stop bleeding. Conclusion:Professor Wang Pei mostly discusses the treatment of colon cancer from "spleen dampness, rectification deficiency, heat toxin, blood stasis, bleeding", and the treatment is "invigorating the spleen and removing dampness, invigorating Qi and strengthening the body, clearing away heat and detoxifying, promoting blood circulation and removing blood stasis, and astringent intestines to stop bleeding", which is in line with the thought of Traditional Chinese Medicine treatment of tumors, strengthening the righteousness and eliminating pathogenic factors, and and can be used for clinical reference.

ObjectiveTo analyze the characteristics of tradition Chinese medicine (TCM) syndromes in patients with urolithiasis. MethodA syndrome questionnaire was developed to collect the general data and four diagnosis information on 296 patients with urolithiasis who were treated from September 2021 to September 2022. Tongue images, pulse images, symptoms, and signs were statistically analyzed, and the characteristics of syndrome were explored by association rule analysis, factor analysis, and cluster analysis. Result① In the distribution of tongue images, the single tongue images with a frequency of more than 20% were white fur, red tongue, thick fur, greasy fur, and yellow fur. In the distribution pf pulse images, the single pulse with the frequency of more than 20% was fine pulse, string pulse, slippery pulse, and sinking pulse. There were 27 symptoms and signs with a frequency of more than 10%. The characteristic symptoms of acute onset such as lumbar and abdominal pain and nausea, frequent urination, hematuria, and poor urination were relatively common, and other symptoms were chill and fever, defecation, and digestion. ② Among the 14 strong association rules, 5 were yang-deficiency and cold-dampness syndromes, 4 were yin-deficiency and heat syndromes, 1 was kidney-deficiency syndrome, and 3 were renal colic with accompanying symptoms. ③ Sixteen common factors were extracted by factor analysis, and the main elements of the disease location were represented by spleen and kidney. The main elements of disease natures were Yin deficiency, Yang deficiency, dampness, and heat, and often mixed with deficiency-excess in complexity. Six syndromes were obtained by cluster analysis, and the represented syndromes were mainly kidney deficiency and dampness and stasis, Qi stagnation and heat accumulation, Yin deficiency and dampness heat, spleen-kidney Yang deficiency, spleen deficiency and dampness, and dampness-heat accumulation. ConclusionThe syndrome manifestations of urolithiasis are chill and fever, defecation, sweating, and digestive tract symptoms. The deficiency syndromes are mainly Yin deficiency, Yang deficiency, kidney deficiency, and spleen deficiency. The excess syndromes are mainly wet and heat. The deficiency and excess syndromes often exist simultaneously. The spleen deficiency is the important pathogenesis of urolithiasis besides the kidney deficiency.

Objective::This study investigates the efficacy of analyzing fetal heart rate (FHR) signals based on Artificial Intelligence to obtain a baseline calculation and identify accelerations/decelerations in the FHR through electronic fetal monitoring during labor.Methods::A total of 43,888 cardiotocograph(CTG) records of female patients in labor from January 2012 to December 2020 were collected from the NanFang Hospital of Southern Medical University. After filtering the data, 2341 FHR records were used for the study. The ObVue fetal monitoring system, manufactured by Lian-Med Technology Co. Ltd., was used to monitor the FHR signals for these pregnant women from the beginning of the first stage of labor to the end of delivery. Two obstetric experts together annotated the FHR signals in the system to determine the baseline as well as accelerations/decelerations of the FHR. Our cardiotocograph network (CTGNet) as well as traditional methods were then used to automatically analyze the baseline and acceleration/deceleration of the FHR signals. The results of calculations were compared with the annotations provided by the obstetric experts, and ten-fold cross-validation was applied to evaluate them. The root-mean-square difference (RMSD) between the baselines, acceleration F-measure (Acc.F-measure), deceleration F-measure (Dec.F-measure), coefficient of synthetic inconsistency (SI) and the morphological analysis discordance index (MADI) were used as evaluation metrics. The data were analyzed by using a paired t-test. Results::The proposed CTGNet was superior to the best traditional method, proposed by Mantel, in terms of the RMSD.BL (1.7935 ± 0.8099 vs. 2.0293 ± 0.9267, t=-3.55 , P=0.004), Acc.F-measure (86.8562 ± 10.9422 vs. 72.2367 ± 14.2096, t= 12.43, P <0.001), Dec.F-measure (72.1038 ± 33.2592 vs. 58.5040 ± 38.0276, t= 4.10, P <0.001), SI (34.8277±20.9595 vs. 54.8049 ± 25.0265, t=-9.39, P <0.001), and MADI (3.1741 ± 1.9901 vs. 3.7289 ± 2.7253, t= -2.74, P= 0.012). The proposed CTGNet thus had significant advantages over the best traditional method on all evaluation metrics. Conclusion::The proposed Artificial Intelligence-based method CTGNet delivers good performance in terms of the automatic analysis of FHR based on cardiotocograph data. It promises to be a key component of smart obstetrics systems of the future.

Objective::This study investigates the efficacy of analyzing fetal heart rate (FHR) signals based on Artificial Intelligence to obtain a baseline calculation and identify accelerations/decelerations in the FHR through electronic fetal monitoring during labor.Methods::A total of 43,888 cardiotocograph(CTG) records of female patients in labor from January 2012 to December 2020 were collected from the NanFang Hospital of Southern Medical University. After filtering the data, 2341 FHR records were used for the study. The ObVue fetal monitoring system, manufactured by Lian-Med Technology Co. Ltd., was used to monitor the FHR signals for these pregnant women from the beginning of the first stage of labor to the end of delivery. Two obstetric experts together annotated the FHR signals in the system to determine the baseline as well as accelerations/decelerations of the FHR. Our cardiotocograph network (CTGNet) as well as traditional methods were then used to automatically analyze the baseline and acceleration/deceleration of the FHR signals. The results of calculations were compared with the annotations provided by the obstetric experts, and ten-fold cross-validation was applied to evaluate them. The root-mean-square difference (RMSD) between the baselines, acceleration F-measure (Acc.F-measure), deceleration F-measure (Dec.F-measure), coefficient of synthetic inconsistency (SI) and the morphological analysis discordance index (MADI) were used as evaluation metrics. The data were analyzed by using a paired t-test. Results::The proposed CTGNet was superior to the best traditional method, proposed by Mantel, in terms of the RMSD.BL (1.7935 ± 0.8099 vs. 2.0293 ± 0.9267, t=-3.55 , P=0.004), Acc.F-measure (86.8562 ± 10.9422 vs. 72.2367 ± 14.2096, t= 12.43, P <0.001), Dec.F-measure (72.1038 ± 33.2592 vs. 58.5040 ± 38.0276, t= 4.10, P <0.001), SI (34.8277±20.9595 vs. 54.8049 ± 25.0265, t=-9.39, P <0.001), and MADI (3.1741 ± 1.9901 vs. 3.7289 ± 2.7253, t= -2.74, P= 0.012). The proposed CTGNet thus had significant advantages over the best traditional method on all evaluation metrics. Conclusion::The proposed Artificial Intelligence-based method CTGNet delivers good performance in terms of the automatic analysis of FHR based on cardiotocograph data. It promises to be a key component of smart obstetrics systems of the future.

BACKGROUND: Both proximal femoral nail and hemiarthroplasty have been applied in the treatment of unstable intertrochanteric fractures in osteoporotic patients. However, which has better curative efficacy is still under discussion.OBJECTIVE: To investigate the clinical effectiveness of proximal femoral nail versus hemiarthroplasty in the treatment of unstable intertrochanteric fracture in osteoporotic patients.METHODS: Sixty-seven patients diagnosised with unstable intertrochanteric fractures and osteoporosis were selected,and were randomly divided into two groups, followed by treated with hemiarthroplasty (group 1, n=35)) and proximal femoral nail (group 2, n=32), respectively. The operation time, intraoperative blood loss, length of incision, postoperative time in bed, hospitalization time and complications were recorded and compared between two groups. Harris hip scores were used to evaluate the preoperative and postoperative hip function.RESULTS AND CONCLUSION: (1) In the group 1, the operation time, intraoperative blood loss and length of incision were more than those in the group 1, and the postoperative time in bed was less than that in the group 2 (P < 0.05).However, the healing and hospitalization time did not differ significantly between two groups (P > 0.05). (2) No significant difference was observed in the excellent and good rate in Harris hip scores between two groups at the last follow-up (P >0.05). The postoperative pain scores in the group 1 were significantly superior to those in the group 2 (P < 0.05). (3)There were 1 case of delayed union and 1 case of lateral hip appearing with pain in the group 2. At the last follow-up, all patients healed completely, and no prosthesis dislocation, loosening or infection was found. (4) To condude,hemiarthroplasty provides early functional recovery and fewer complications, but with much surgical trauma. Proximal femoral nail shows similar treatment outcomes with hemiarthroplasty; therefore, it is a kind of alternative treatment strategy for unstable intertrochanteric fractures.

The incidence of spine metastasis is increasing due to the aging demography and improvement of cancer diagnosis and treatments.Spine metastasis is one of the serious complications of advanced cancers,and its treatment should pay attention to patients' quality of life and consider interdisciplinary cooperation.Expected life span can guide doctors to select the appropriate treatment for spine metastasis patients,and various scoring systems have been developed.We elicited relevant literatures in WanFang,CNKI,PubMed and Embase databases.Articles aiming at developing model for spine metastasis or describing the clinical effectiveness and pitfalls of the existed systems were included.As a result,48 articles were carefully reviewed.In this review,thosc scoring systems were stratified into two groups:Traditional scoring systems,which were published before or in 2005,including original/revised Tokuhashi scoring systems,Tomita scoring system,Bauer scoring system,Linden scoring system,and Sioutos scoring system;and new scoring systems,which were designed during the last three years,including Lei & Liu scoring system,Bollen scoring system,Rades scoring system,Oswestry spinal risk index (OSRI),and Katagiri scoring system.The usefulness of the traditional scoring systems has been validated by many studies.However,the applicability of those scoring system were controversial due to improvement of cancer treatment and survival period in recent years.Although the improvement of life span was considered,those new scoring systems have not penetrated into clinical routine because of the lack of validation.Currently,which system has the highest accuracy rates still remains unclear.Next generation of scoring systems should take into account the practicality and reliability at the same time.In this review,we introduced above mentioned scoring systems,described the validity and limitation of those scoring system,and suggested the future directions of next generation of scoring systems.

BACKGROUND:Core decompression and tantalum rod implantation after core decompression are common methods to repair early and middle stages of necrosis of femoral head, can effectively control and even reverse the progress of necrosis of the femoral head. Comparison of mechanical support and curative effect of femoral head after operation deserves further investigation. OBJECTIVE:To explore the effect of core decompression on mechanical pulp femoral head support by using the finite element analysis and the advantages of tantalum implant treatment in the repair of avascular necrosis of the femoral head. METHODS: The right femur of healthy adults was chosen as the research object, and CT scanning was conducted to get the images of cross-sections. The images were then inputted into computer to get contour of femur and rebuild three-dimensional model. Distal end of femur was completely fixed, the angle of the top of femoral head and the femoral shaft was 25°, and 570 N pressure on the femoral head was applied according to the three-dimensional space distribution of femur force under physiological state. Three-dimensional finite element models were calculated to get the colapse values in different necrotic areas of the femoral head before and after different repair methods. RESULTS AND CONCLUSION:After core decompression, colapse values were apparently increased, especialy in the weight-bearing area. With increased range of necrosis, colapse values also increased. After core decompression, colapse values decreased obviously after porous tantalum rod implantation. Although core decompression could remove dead bone, decompression itself further reduced the mechanical properties of the femoral head and changed the original femoral head support. On the basis of core decompression, porous tantalum rod provided safe and effective mechanical support for femoral head and subchondral bone plate, could effectively prevent colapse and provide conditions for the restoration of bone tissue.