OBJECTIVE: To analyze the significance of total vitamin D (tVD), total procollagen type I amino-terminal propeptide (tPINP) and β-CrossLaps (β-CTx) in the staging and prognosis of patients with multiple myeloma (MM). METHODS: A total of 54 patients with newly diagnosed MM admitted to the Second Affiliated Hospital of Fujian Medical University from 2020 to 2022 were selected as the observation group (MM group), and 50 healthy persons who underwent physical examinations in our hospital were selected as the control group. The expression levels of tVD, tPINP and β-CTx in the two groups were detected by chemiluminescence method. The differences in the expression levels of tVD, tPINP and β-CTx among MM patients at different ISS stages were analyzed. The expression levels of tVD, tPINP and β-CTx in MM patients with different levels of hemoglobin (Hb), serum calcium (Ca), creatinine (Crea), albumin (ALB), β₂-microglobulin (β₂-MG) and lactate dehydrogenase (LDH) were compared. The correlations between the expression levels of tVD, tPINP, β-CTx and the aforementioned clinical parameters were analyzed, respectively. The relationship between the expression levels of tVD, tPINP, β-CTx and the progression-free survival (PFS) of MM patients was analyzed. RESULTS: The expression level of tVD in the MM group was significantly lower than that in the control group (21.73±14.45 ng/ml vs 30.78±9.94 ng/ml, P =0.022). The expression level of β-CTx in the MM group was significantly higher than that in the control group (1.43±0.99 ng/ml vs 0.53±0.29 ng/ml, P =0.013). The tVD level in MM patients with ISS stage I-II was significantly higher than that of MM patients with ISS stage III (29.50±14.59 ng/ml vs 12.62±7.73 ng/ml, P =0.028), indicating that the higher the ISS stage, the lower the tVD level. The tPINP and β-CTx levels in MM patients with high Ca levels (>2.65 mmol/L) were significantly higher than those in patients with low Ca levels (≤2.65 mmol/L) (P =0.016, P =0.021). The tVD level of MM patients was positively correlated with the ALB level (r =0.570), tPINP was positively correlated with Ca and β₂-MG levels (r =0.791,r =0.673), and β-CTx was positively correlated with tPINP level (r =0.616). The PFS of the low tVD expression group was significantly lower than that of the high tVD expression group (P =0.041). CONCLUSION The expression level of tVD is decreased in MM patients, which can be used as an indicator to evaluate the disease stage and prognosis of the patients. The β-CTx expression level is increased in MM patients. tPINP and β-CTx may be correlated with clinical symptoms such as osteolytic lesions and renal function changes in MM patients.
Humans ; Multiple Myeloma/pathology* ; Procollagen/blood* ; Vitamin D/blood* ; Prognosis ; Peptide Fragments/blood* ; Collagen Type I/blood* ; Female ; Male ; Middle Aged ; Aged ; Neoplasm Staging

OBJECTIVE: To investigate lymph node metastasis (LNM) in the prostatic anterior fat pad (PAFP) of PCa patients after robot-assisted radical prostatectomy (RARP), and analyze the clinicopathological features and prognosis of LNM in the PAFP. METHODS: We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urology of PLA General Hospital from January 2017 to December 2022. All the patients underwent routine removal of the PAFP during RARP and pathological examination, with the results of all the specimens examined and reported by pathologists. Based on the presence and locations of LNM, we grouped the patients for statistical analysis, compared the clinicopathological features between different groups using the Student's t, Mann-Whitney U and Chi-square tests, and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio. RESULTS: Lymph nodes were detected in 77 (7.7%) of the 1 003 PAFP samples, and LNM in 11 (14.3%) of the 77 cases, with a positive rate of 1.1% (11/1 003). Of the 11 positive cases, 9 were found in the upgraded pathological N stage, and the other 2 complicated by pelvic LNM. The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group (81.8% ［9/11］ vs 36.2% ［359/992］, P = 0.005), and so did the cases with Gleason score ≥8 (87.5% ［7/8］ vs 35.5% ［279/786］, P = 0.009). No statistically significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the patients with PAFP LNM only and those with pelvic LNM only. CONCLUSION The PAFP is a potential route to LNM, and patients with LNM in the PAFP are characterized by poor pathological features. There is no statistically significant difference in biochemical recurrence-free survival between the patients with PAFP LNM only and those with pelvic LNM only. Routine removal of the PAFP and independent pathological examination of the specimen during RARP is of great clinical significance.
Humans ; Male ; Prostatectomy/methods* ; Robotic Surgical Procedures ; Lymphatic Metastasis ; Retrospective Studies ; Prognosis ; Prostatic Neoplasms/pathology* ; Adipose Tissue/pathology* ; Prostate/pathology* ; Lymph Nodes/pathology* ; Middle Aged ; Aged

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective To analyze the diagnostic process and clinical characteristics of autoimmune gastritis(AIG)in order to improve the awareness and diagnostic proficiency of this disease.Methods A retrospective cohort study was conducted on 114 patients diagnosed with AIG in Army Medical Center of PLA between January 2021 and June 2024.Comprehensive statistical analysis was performed on clinical data,including demographic characteristics(age,sex),clinical symptoms,comorbidities,diagnostic process,Helicobacter pylori(H.pylori)infection and treatment history,laboratory indicators[results of routine blood test,anemia-related indices,thyroid function,anti-parietal cell antibody(APCA),intrinsic factor antibody(IFA)],and gastrointestinal endoscopic findings(frequency and endoscopic features).Results Among the 114 patients,males accounted for 28.1%(32/114)and females for 71.9%(82/114),and they were at a mean age of 56.3±8.4 years.Predominant symptoms included epigastric/upper abdominal pain(47.4%,54/114)and postprandial fullness(43.0%,49/114),while 24.6%(28/114)reported acid reflux or heartburn.Diagnostic delay occurred in 76.4%(87/114)of patients,with a median delay duration of 11.5 months.Primary diagnostic clues were endoscopic reverse gradient atrophy(significantly more severe mucosal atrophy in the gastric corpus/fundus versus antrum;53.5%,61/114)and repeated H.pylori eradication failure(≥2 attempts;22.8%,26/114).Positivity rate of thyroid peroxidase antibody(TPOAb)and thyroglobulin antibody(TgAb)was 56.9%(33/58)and 36.2%(21/58),respectively.APCA positive rate was 98.8%(81/82),IFA positive rate was 34.1%(28/82),and dual-antibody rate was 32.9%(27/82).Anemia was present in 25.7%(26/101)of the patients.Gastric neuroendocrine tumors(NET)were found in 12.2%(14/114),intraepithelial neoplasia in 5.3%(6/114),and gastric adenocarcinoma in 0.9%(1/114).Among colonoscopy-examined patients,tubular adenomas occurred in 25.0%(13/52)and colorectal malignancies in 3.4%(2/58).There were 18.4%(21/114)patients having gallbladder-related diseases,7.9%(9/114)having diabetes mellitus,and 1.8%(2/114)of subacute combined degeneration of the spinal cord.Conclusion AIG is frequently associated with diagnostic delay.The reverse pattern of atrophy on endoscopy serves as a critical diagnostic clue,necessitating enhanced recognition in endoscopists.Patients with recurrent H.pylori eradication failure(≥2 attempts)should be evaluated for AIG.

Objective: To investigate the protective effects and mechanisms of acellular nerve allografts (ANA) on motor neurons in the spinal cord anterior horn of sciatic nerve injury ( SNI) rats . Methods: SPF grade male SD rats were randomly divided into normal , model , ANA-bridged (bridge group) , and autologous nerve transplantation groups (autograft group) , with 6 rats in each group . The SNI rat model was established using the right sciatic nerve clamp method for 10 mm . In the bridge group , the ANA was bridged to the two severed ends of the injured sciatic nerve , and in the autograft group , the autologous nerves were flipped head to tail and then bridged to the two se- vered ends . A spectrophotometer was applied to determine the DNA content in normal nerves and ANA . The foot- print test was used to determine the sciatic nerve function index (SFI) of the rats in each group , the wet weight ra- tio of the anterior tibialis muscle was calculated . The morphology and structure of the anterior horn motor neurons of the spinal cord of each group were observed by HE staining. The immunofluorescence and Western blot were used to detect Apaf-1 , Caspase-3 , Bcl-2 , Bax , and Cyt-C proteins expression in the L4-6 segment of the spinal cord . Results: The DNA content in the ANA prepared in this study was significantly lower than that in normal nerves (P < 0. 05) . Compared with the normal group , the SFI and wet weight ratio of the anterior tibialis muscle were re- duced in the model group (P < 0. 001) ; compared with the model group , both SFI and wet weight ratio of the ante- rior tibialis muscle significantly increased in the bridge group and the autografts group ( P < 0. 05 , P < 0. 001) , and the SFI and wet weight ratio of the anterior tibialis muscle in the autograft group were higher than those in the bridge group (P < 0. 001 , P < 0. 01) . The results of HE staining showed that the motor neurons in the anterior horn of the spinal cord of the normal group were structurally intact and had clear cytosolic boundaries; the neurons in the model group were lysed and necrotic , with blurred cytosolic boundaries; the neurons in the bridge group were less lysed and necrotic , but the nuclear translocation phenomenon could still be seen; the neurons in the autograft group were morphologically and structurally intact with clear cytosolic boundaries . Compared with the normal group , the expression of Apaf-1 , Caspase-3 , Bax and Cyt-C proteins significantly increased in the model group (P < 0. 001 , P < 0. 01 , P < 0. 01 , P < 0. 05) . Compared with the model group , the expression of Apaf-1 , Caspase- 3 , Bax , and Cyt-C proteins significantly decreased (P < 0. 001 , P < 0. 05 , P < 0. 05 , P < 0. 05) ; but the expres- sion of Bcl-2 protein significantly increased in the bridge group and the autograft group (P < 0. 05) . The expression of Apaf-1 , Caspase-3 , Bax and Cyt-C proteins in the autografts group was lower than that in the bridge group (P < 0. 001 , P < 0. 05 , P < 0. 05 , P < 0. 05) . Conclusion ANA can exert a protective effect on motor neurons in the anterior horn of the spinal cord of SNI rats by improving the morphology and structure of neurons , increasing the ex- pression of Bcl-2 protein , but decreasing the expression of Cyt-C , Bax , Caspase-3 , and Apaf-1 proteins in the spi- nal cord . The mechanism of ANA may be related to the Bcl-2/Cyt-C/Apaf-1-mediated mitochondrial apoptosis sig- naling pathway .

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

BACKGROUND:As tissue engineering brings new hope to the worldwide problem of articular cartilage repair,the construction of light-curing 3D printed hydrogel scaffolds with biomimetic composition is of great significance for cartilage tissue engineering. OBJECTIVE:To construct a biomimetic methacryloylated hyaluronic acid/acellular Wharton's jelly composite hydrogel scaffold by digital light processing 3D printing technology,and to evaluate its biocompatibility. METHODS:Wharton's jelly was isolated and extracted from human umbilical cord,then decellulated,freeze-dried,ground into powder,and dissolved in PBS to prepare 50 g/L acellular Wharton's jelly solution.Methylallylated hyaluronic acid was prepared,lyophilized and dissolved in PBS to prepare 50 g/L methylallylated hyaluronic acid solution.Acellular Wharton's jelly solution was mixed with methacrylyacylated hyaluronic acid solution at a volume ratio of 1:1,and was used as bio-ink after adding photoinitiator.Methylacrylylated hyaluronic acid hydrogel scaffolds(labeled as HAMA hydrogel scaffolds)and methylacrylylated hyaluronic acid/acellular Wharton's jelly gel scaffolds(labeled as HAMA/WJ hydrogel scaffolds)were prepared by digital light processing 3D printing technology,and the microstructure,swelling performance,biocompatibility,and cartilage differentiation performance of the scaffolds were characterized. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the two groups of scaffolds showed a three-dimensional network structure,and the fiber connection of HAMA/WJ hydrogel scaffold was more uniform.Both groups achieved swelling equilibrium within 10 hours,and the equilibrium swelling ratio of HAMA/WJ hydrogel scaffold was lower than that of HAMA hydrogel scaffold(P＜0.05).(2)CCK-8 assay showed that HAMA/WJ hydrogel scaffold could promote the proliferation of bone marrow mesenchymal stem cells compared with HAMA hydrogel scaffold.Dead/live staining showed that bone marrow mesenchymal stem cells grew well on the two groups of scaffolds,and the cells on the HAMA/WJ hydrogel scaffolds were evenly distributed and more cells were found.Phalloidine staining showed better adhesion and spread of bone marrow mesenchymal stem cells in HAMA/WJ hydrogel scaffold than in HAMA.(3)Bone marrow mesenchymal stem cells were inoculated into the two groups for chondrogenic induction culture.The results of qRT-PCR showed that the mRNA expressions of agglutinoglycan,SOX9 and type Ⅱ collagen in the HAMA/WJ hydrogel scaffold group were higher than those in the HAMA hydrogel scaffold group(P＜0.05,P＜0.01).(4)These findings indicate that the digital light processing 3D bioprinting HAMA/WJ hydrogel scaffold can promote the proliferation,adhesion,and chondrogenic differentiation of bone marrow mesenchymal stem cells.

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.