Objective:To explore the relationship between corrected serum calcium level and clinical characteristics in patients with newly-diagnosed multiple myeloma (MM), as well as the influencing factors of concomitant hypercalcemia.Methods:A retrospective case cohort study was conducted. The clinical data of newly-diagnosed MM patients who were admitted to Shanxi Province Cancer Hospital from January 2020 to December 2023 were collected. When serum albumin (ALB) was less than 40 g/L, the serum calcium level was corrected. The hypercalcemia group was defined as the corrected serum calcium level >2.60 mmol/L, the normal blood calcium group was defined as 2.20-2.60 mmol/L, and the hypocalcemia group was defined as <2.20 mmol/L; the combination of normal blood calcium group and hypocalcemia group was the non-hypercalcemia group. The age, gender, immune typing, ALB, blood urea nitrogen (BUN), serum creatinine (Scr), β 2-microglobulin (β 2-MG), and alkaline phosphatase (ALP) of patients in the hypercalcemia group and the non-hypercalcemia group were compared. Pearson correlation analysis was used for the correlation analysis. The logistic regression model was used to conduct multivariate analysis on the influencing factors of hypercalcemia. Results:Before correction, there were 31 cases (26.5%), 48 cases (40.0%) and 38 cases (32.5%) of MM patients in the hypocalcemia group, normal blood calcium group and hypercalcemia group, respectively. After correction, there were 17 cases (14.5%), 58 cases (49.6%) and 42 cases (35.9%), respectively. The corrected serum calcium level for male MM patients was (2.58± 0.41) mmol/L, while for females it was (2.53±0.38) mmol/L, and there was no statistically significant difference between the two groups ( t = 0.79, P > 0.05). The corrected serum calcium levels for patients in stage Ⅰ, stage Ⅱ and stage Ⅲ of the International Staging System (ISS) were (2.31±0.15) mmol/L, (2.52±0.37) mmol/L and (2.65±0.42) mmol/L, respectively, and the difference between the three groups was statistically significant ( F = 53.62, P < 0.01). Corrected serum calcium showed a negative correlation with patients' serum ALB ( r = -0.201, P < 0.05), and positive correlations with Scr, BUN and β 2-MG levels ( r values were 0.470, 0.247 and 0.469, respectively, all P < 0.01), but it had no correlation with age or ALP ( r values were -0.013 and 0.078, respectively, both P > 0.05). There were 15 cases (17.1%), 48 cases (54.5%) and 25 cases (28.4%) of patients with normal renal function in the hypocalcemia group, normal blood calcium group and hypercalcemia group, respectively; there were 2 cases (6.9%), 10 cases (34.5%) and 17 cases (58.6%) of patients with impaired renal function in the hypocalcemia group, normal blood calcium group and hypercalcemia group, respectively; there were statistically significant differences between the hypocalcemia group and the hypercalcemia group, as well as between the normal blood calcium group and the hypercalcemia group ( χ2 = 4.57, P < 0.05; χ2 = 6.67, P < 0.05), but there was no statistically significant difference between the hypocalcemia group and the normal calcium group ( χ2 = 0.29, P>0.05). The patients with approximately normal bone status in the hypocalcemia group, normal blood calcium group and hypercalcemia group were 3 cases (13.0%), 17 cases (74.0%) and 3 cases (13.0%), respectively, and the patients with bone damage were 14 cases (14.9%), 41 cases (43.6%), and 39 cases (41.5%), respectively, and there was a statistically significant difference between the normal blood calcium group and the hypercalcemia group ( χ2 = 7.48, P < 0.01), while there was no statistically significant difference between the hypocalcemia group and the hypercalcemia group ( χ2 = 1.46, P > 0.05). The proportions of patients with Scr > 177 μmol/L and β 2-MG > 3.5 mg/L in the hypercalcemia group were higher than those in the non-hypercalcemia group, and the differences were statistically significant (both P < 0.05). The results of logistic regression multivariate analysis showed that β 2-MG >3.5 mg/L was an independent risk factor for hypercalcemia in newly-diagnosed MM patients ( OR = 1.178, 95% CI: 1.058-1.311, P = 0.003). Conclusions:Corrected serum calcium level may be an important indicator for evaluating the severity of disease, renal function and bone status in newly-diagnosed MM patients.

Objective : To investigate the partial mechanism and effect of transplanting with human umbilical cordderived mesenchymal stem cells (hUC⁃MSCs) to repair articular cartilage defects in a rat model. Methods : Critical⁃sized osteochondral defects were created in the trochlear grooves of rat femurs. The hUC⁃MSCs were transplanted into the defect of experimental knees. Sham group and model group knees were transplanted with saline. The effects of articular cartilage repair were evaluated at 10 weeks after surgery with International Cartilage Repair Society (ICRS) repair score , histological examination and immunohistochemical analysis. The effects of hUC⁃MSCs on the proliferation and migration of chondrocytes were detected by Transwell in vitro. Results : After transplanting with hUC⁃MSCs , the articular surfaces of the defect sites were changed smoother thanthose of the model group , and the cellular morphology and arrangement were also improved in Safranin O staining or Masson staining results. Similar to surrounding normal articular cartilage tissue after treatment for 10 weeks , and the ICRS repair score was signifision of type Ⅱ (Col Ⅱ ) collagen and decrease the level of type Ⅰ collagen( Col Ⅰ ) in the articular defect site. Meanwhile , the increased protein expression of SOX9 and protein transportation to the nucleus were observed after treatment with hUC⁃MSCs for 10 weeks. In vitro , chondrocytes could be proliferated and migrated after co⁃cultured with hUC⁃MSCs. Conclusion Transplanting with hUC⁃MSCs can promote cartilage repair, and its role maybe related to the protection of the cartilage matrix and the promotion of chondrocyte proliferation and migration.

Objective : To study the protective effect and mechanism of iPSC⁃MSCs on cartilage matrix in knee oste⁃ oarthritis (KOA) patients in vitro. Methods : Cartilage tissues removed from KOA patients with joint replacement surgery were collected and subjected to tissue and cellular experiments , respectively. Cartilage tissue was cut into small pieces and randomly divided into a control group , an IL⁃1β ( 10 ng/ml) induction group , and iPSC⁃MSCs 96 h and then co⁃cultured with different amounts of iPSC⁃MSCs ( 1 × 104 , 1 × 105 , 1 × 106 ) cells for 72 h. For in tissues , the pathological changes of isolated cartilage tissues were examined by HE staining. The levels of ADAMTS⁃4 , ADAMTS⁃5 , and type II collagen expression were analyzed by immunohistochemistry , while the levels of MMP13 , IL⁃6 , and IL⁃10 in culture supernatants were detected by ELISA kits. The 2 to 5 generations of chondrocytes , which were extracted from cartilage tissue of KOA patients , were stimulated with IL⁃1β ( 10 ng/ml) for 48 h and then co⁃cultured with different concentrations of iPSC⁃MSCs ( 1 × 104 , 1 × 105 , 1 × 106 ) cells for 72 h. Immunofluorescence and Western blot detected the expression of RUNX2 , ADAMTS⁃4 , and ADAMTS⁃5 in chondrocytes. Results : Comparison with the control group , in the IL⁃1β⁃induced group , the levels of RUNX2 , ADAMTS⁃4 , and ADAMTS⁃5 increased , the level of type II collagen decreased , the levels of MMP⁃13 and IL⁃6 in the culture supernatant increased ( P < 0. 05) , and the level of IL⁃10 decreased ( P < 0. 05) ; Compared with the IL⁃1β⁃induced decreased the expression of RUNX2 , ADAMTS⁃4 , and ADAMTS⁃5 , promoted type II collagen expression and elevated IL⁃10 levels. Conclusion iPSC⁃MSCs inhibited ADAMTS⁃4 and ADAMTS⁃5 expression in vitro , reduced cartilage extracellular matrix degradation , and played a role in articular cartilage protection.

Objective: To establish and evaluate the pyroptosis model of rat chondrocytes induced by tumor necrosis factor-α(TNF-α). Methods: A two-step enzymatic digestion method was used to obtain rat articular chondrocytes, inverted phase contrast microscope was used to observe the morphological structure of chondrocytes. Toluidine blue staining and type Ⅱ collagen(Col Ⅱ) staining were used to identify chondrocytes. Different mass concentrations of TNF-α(5, 10, 20, 40 ng/ml) were used to establish the pyroptosis model with TNF-α(0 ng/ml) as the control group. Cell viability was detected by CCK-8 method and proteins of pyroptosis signal were detected by Western blot. The levels of IL-1β and IL-18 in cultured supernatants were examined by ELISA kits. The expression of gasdermin D(GSDMD) in chondrocytes was detected by immunofluorescence. Scanning electron microscope was used to observe the morphological changes of chondrocyte. Results: Compared with the control group, the cell viability of rat chondrocytes gradually decreased with the increase of TNF-α concentration and the expression of nucleotide-binding and oligomerization domain-like receptor containing protein 3(NLRP3), caspase-1, GSDMD and Phospho-NF-κB p65(P-p65) proteins increased. Furthermore, TNF-α(20 ng/ml) could up-regulate the expression of matrix metalloproteinase-13(MMP-13), the fluorescence expression of GSDMD and the levels of IL-1β and IL-18 while the expression of Col Ⅱ was distinctly reduced. What′s more, the articular chondrocytes were swollen,and the microstructure was destroyed. Conclusion TNF-α(20 ng/ml) can cause the swelling and death of rat chondrocytes, degradation of cartilage matrix and activation of pyroptosis signaling pathway. The pyroptosis model of rat chondrocytes was successfully established.

Objective:To analyze the clinical phenotype and molecular pathogenesis of nine patients with hereditary factor Ⅴ (FⅤ) deficiency.Methods:Nine patients with hereditary FⅤ deficiency who were admitted to the Institute of Hematology and Blood Diseases Hospital from April 1999 to September 2019 were analyzed. The activated partial thromboplastin time, prothrombin time, and FⅤ procoagulant activity (FⅤ∶C) were measured for phenotypic diagnosis. High-throughput sequencing was employed for the F5 gene mutation screening, Sanger sequencing was adopted to confirm candidate variants and parental carrying status, Swiss-model was used for three-dimensional structure analysis, and ClustalX v.2.1 was used for homologous analysis.Results:The FⅤ∶C of the nine patients ranged from 0.1 to 10.6. Among them, eight had a hemorrhage history, with kin/mucosal bleeding as the most common symptom (three cases, 37.5%) , whereas one case had no bleeding symptom. There were five homozygotes and four compound heterozygotes. A total of 12 pathogenic or likely pathogenic mutations were detected, of which c.6100C>A/p.Pro2034Thr, c.6575T>C/p.Phe2192Ser, c.1600_1601delinsTG/p. Gln534*, c.4713C>A/p.Tyr1571*, and c.952+5G>C were reported for the first time.Conclusion:The newly discovered gene mutations enriched the F5 gene mutation spectrum associated with hereditary FⅤ deficiency. High-throughput sequencing could be an effective method to detect F5 gene mutations.

Ras-associated domain family 1A (RASSF1A) genes are members of the RASSF family, which bind to Ras in a guanosine triphosphate(GTP)-dependent manner and then induce Ras-mediated apoptosis. The protein encoded by the RASSF1A gene is similar to the Ras effector protein, which can interact with DNA repair protein XPA, and can also inhibit the accumulation of cyclin D1, thereby inducing cell cycle arrest. The deletion or abnormal expression of RASSF1A gene is related to the pathogenesis of various malignant tumors, indicating that it has tumor suppressor function. RASSF1A gene methylation has been found in at least 37 tumors, and RASSF1A gene may be the most frequently described methylated gene in human cancers. In this paper, the abnormal methylation of RASSF1A gene in different malignant tumors was introduced, and the research progress of its related effects and mechanisms in malignant tumors of the respiratory system, digestive system, genitourinary system, and nervous system in recent years was reviewed, with a view to malignant tumors early diagnosis, individual molecular targeted therapy and prognostic evaluation provide important guidance.

Objective To illustrate the semiological characteristics of the three sub-types within the broad bilateral asymmetric tonic seizures (BATS),summarize their predictive values on lateralization and localization of seizure onset zone (SOZ),and analyze the difference between BATS and asymmetrical tonic limb posturing (ATLP).Methods A retrospective review of 385 patients who underwent stereotactic electrode implantation in the Sanbo Brain Hospital,Capital Medical University from September 2011 to May 2018 was performed.As long as there was a clinical epileptic seizure in the presence of BATS or ATLP,the patients were classified into the corresponding groups.Postoperative prognosis was assessed using Engel's grading criteria for a follow-up of no less than six months.Seizure descriptions were based on the classification of epileptic seizures introduced by Lüiders,which used arrows to connect the symptoms in chronological order.Results There was no statistically significant difference between the classic BATS and bilateral proximal tonic seizure in terms of whether it could be an independent seizure,as the onset and end of the seizure,with version and generalized tonic-clonic seizure (P＞0.05).Compared with the ATLP,except for whether it could be an independent seizure (P=1.000) and onset before versive seizure (P=0.068),the BATS showed significantly different semiological features (P＜0.05).The classic BATS and secondary motor area epilepsy had a 100.0％ predictive accuracy on the lateralization of SOZ.In the patients with broad BATS,the SOZ distribution was more extensive,but it was rare in the orbitofrontal gyrus,frontal pole and mesial temporal lobe.Compared with the bilateral proximal tonic seizures from the other regions,those originated from supplementary somatosensory motor area and its adjacent areas were rare and showed no statistically significant difference (0/8 vs 40.0％ (18/45),x2=3.226,P=0.072) but a low trend.The predictive value of BATS on lateralization of SOZ was higher than that of ATLP (84.9％ (45/53) vs 57.1％ (24/42),x2=9.086,P=0.003),and BATS was less originated from temporal lobe than ATLP (3.8％ (2/53) vs 23.8％ (10/42),x2=8.523,P=0.004).Conclusion Different from ATLP,the broad BATS are characterized by tonic proximal upper limb posturing,and have a higher predictive value on lateralization and localization of SOZ.

Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum. The impact of gene mutation on the patients’ overall survival (OS) and recurrence free survival (RFS) was analyzed by the putative mutations through Kaplan-Meier, and Cox regression methods. Results: Of the 113 patients, 103 (92.0%) harbored at least one mutation and 29 (25.6%) harbored more than 3 genes mutation. The five most frequently mutated genes in B-ALL are SF1, FAT1, MPL, PTPN11 and NRAS. Gene mutations are different between Ph⁺ B-ALL and Ph^- B-ALL patients. Ph^- B-ALL patients with JAK-STAT signal pathway related gene mutation, such as JAK1/JAK2 mutation showed a poor prognosis compared to the patients without mutation (OS: P=0.011, 0.001; RFS: P=0.014,<0.001). Patients with PTPN11 mutation showed better survival than those without mutation, but the difference was not statistically significant (P value > 0.05). Besides, in Ph⁺ B-ALL patients whose epigenetic modifications related signaling pathway genes were affected, they had a worse prognosis (OS: P=0.038; RFS: P=0.047). Conclusion Gene mutations are common in adult ALL patients, a variety of signaling pathways are involved. The frequency and spectrum are varied in different types of B-ALL. JAK family gene mutation usually indicates poor prognosis. The co-occurrence of somatic mutations in adult B-ALL patients indicate the genetic complex and instability of adult B-ALL patients.

Objective: To investigate the feasibility of multiplex real-time RT-PCR with fluorescent probes in early screening of Ph-like acute lymphoblastic leukemia (ALL) and analyze the clinical feature and prognos. Method: A total of 118 adult B-ALL patients diagnosed between October 2010 and March 2016 were enrolled in this study. Multiplex RT-PCR was used to detect the Ph-like ALL related fusion gene and CRLF2 expression in 58 BCR-ABL and MLL rearrangement negative patients. The clinical features, treatment response and prognosis were analyzed in Ph-like fusion gene positive and/or CRLF2 over-expression patients. Result: Among 58 patients, 9 patients (9/58, 15.5%) showed Ph-like ALL related fusion genes positive and 10 patients (10/58, 17.2%) showed CRLF2 over-expression. There were statistical differences in age, WBC count, immunophenotypes, cytogenetics and risk stratification among Ph-like fusion gene positive or CRLF2 over-expression patients, Ph⁺ patients, MLL⁺ patients and B-other patients. The 2-year overall survival rates were 65%, 47%, 64% and 74% respectively among these four groups (P=0.043) . The 2-year relapse free survival rates were 51%, 39%, 62% and 70% respectively among these four groups (P=0.010) . Conclusion Routine screening of Ph-like ALL by multiplex RTPCR is feasible.

Objective To investigate the effects of "one to one" tutorial system of two-way selection model in the standardized training of new nurses.Methods Using purposive sampling, a total of 25 new nurses recruited in July 2014 were selected as the control group,and they received traditional teaching mode. Another 25 new nurses recruited in July 2015 were selected as the observation group,and they received "one to one" tutorial system of two-way selection model. The theoretical and operating scores,general self-efficacy and career self-efficacy of nurses were compared between two groups after one year's training.Results The sores of basic theory,basic operation,professional theory and bedside practice in the observation group were (89.99±5.76), (90.08±2.56),(88.39±6.71) and (92.74±4.30),which were significantly higher than (85.61±6.27),(87.99±3.27),(84.30±5.74) and (89.22±3.55) in the control group (t=2.105,2.296,2.591,2.543;P<0.05). There was no significant difference between two groups in the scores of general self-efficacy,educational requirements and job duties before the training (P>0.05). After one year's training,the scores of general self-efficacy,educational requirements and job duties in the observation group were (31.48±3.12),(15.24±2.16) and (15.64±2.48),which were significantly higher than (26.96±3.54),(11.66±2.54) and (12.40±2.50) in the control group (t=3.901,4.177 and 4.825;P<0.01).Conclusions "One to one" tutorial system of two-way selection model in the standardized training of new nurses could make new nurses change from students to qualified nurses faster and it is worth to be expanded.