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.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis (KOA) model. Methods: Rabbits (n = 18) were randomly divided into control, KOA, and KOA + acupotomy (Apo) groups (n = 6). The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks. After modeling, the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis, vastus lateralis, rectus femoris, biceps femoris, and anserine bursa tendons around the knee. The behavior of all animals was recorded, rectus femoris tissue was obtained, and histomorphological changes were observed using Masson staining and transmission electron microscopy. The expression of transforming growth factor-β1 (TGF-β1), Smad 3, Smad 7, fibrillar collagen types I (Col-I) and III (Col-III) was detected using Western blot and real-time polymerase chain reaction (RT-PCR). Results: Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris, compared with the KOA group (P = .034). Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA, thus preventing skeletal muscle fibrosis. Western blot and RT-PCR analysis revealed that in the Apo group, Col-I, and Col-III protein levels were significantly lower than those in the KOA group (both P < .01), same as Col-I and Col-III mRNA levels (P = .0031; P = .0046). Compared with the KOA group, the protein levels of TGF-β1 and Smad 3 were significantly reduced (both P < .01), as were the mRNA levels of TGF-β1 and Smad 3 (P = .0007; P = .0011). Conversely, the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group (P < .01; P = .0271). Conclusion Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.

Objective:This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed multiple myeloma (NDMM) .Methods:The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed.Results:Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glomerular filtration rate of six patients with RI-NDMM were also improved. During daratumumab maintenance therapy, the most common hematological grade 3 adverse event (AE) was lymphopenia [4 of 15 patients (26.67%) ], whereas the most common nonhematologic AEs were infusion-related reactions [7 of 15 patients (46.67%) ] and grade 3 pneumonia [5 of 15 patients (33.33%) ]. The five patients with pneumonia were daratumumab naive [5 of 13 patients (38.46%) ], with a median of 8 (6-10) infusions. Among them, the chest computed tomography of three patients showed interstitial infiltrates, and treatment with methylprednisolone was effective. With a median follow-up of 12 months, the 1-year overall survival rate was 93.33%, and only one patient died (which was not related to daratumumab treatment) .Conclusions:Daratumumab was safe and effective as a maintenance agent for post-auto-HSCT patients with NDMM, and AEs were controllable. The most common nonhematologic AE was grade 3 pneumonia, and a less dose-intense maintenance regimen for the first 8 weeks could reduce the incidence of pneumonia.

OBJECTIVE: To determine the carrier rate for 21 inherited metabolic diseases among a Chinese population of childbearing age. METHODS: A total of 897 unrelated healthy individuals (including 143 couples) were recruited, and DNA was extracted from their peripheral blood samples. Whole exome sequencing (WES) was carried out to screen potential variants among 54 genes associated with 21 inherited metabolic diseases. Pathogenic and likely pathogenic variants and unreported loss-of-function variants were analyzed. RESULTS: One hundred fourty types of pathogenic/likely pathogenic variants (with an overall number of 183) and unreported loss-of-function variants were detected, which yield a frequency of 0.20 per capita. A husband and wife were both found to carry pathogenic variants of the SLC25A13 gene and have given birth to a healthy baby with the aid of preimplantation genetic diagnosis. The detected variants have involved 40 genes, with the most common ones including ATP7B, SLC25A13, PAH, CBS and MMACHC. Based on the Hardy-Weinberg equilibrium, the incidence of the 21 inherited metabolic diseases in the population was approximately 1/1100, with the five diseases with higher incidence including citrullinemia, methylmalonic acidemia, Wilson disease, glycogen storage disease, and phenylketonuria. CONCLUSION This study has preliminarily determined the carrier rate and incidence of 21 inherited metabolic diseases among a Chinese population of childbearing age, which has provided valuable information for the design of neonatal screening program for inherited metabolic diseases. Pre-conception carrier screening can provide an important measure for the prevention of transmission of Mendelian disorders in the population.
Asians/genetics* ; China ; Exome ; Female ; Humans ; Infant, Newborn ; Metabolic Diseases/genetics* ; Mitochondrial Membrane Transport Proteins/genetics* ; Oxidoreductases/genetics* ; Whole Exome Sequencing

Objective To evaluate the laparoscopic splenectomy and pericardial devascularization in patients with portal hypertension.Methods In this study,205 patients who underwent splenectomy and pericardial devascularization in the Second Hospital of Air Force Medical University between Jan 2013 and Jan 2018 were divided into 135 patients undergoing laparoscopic surgery(LSD group) and 70 patients undergoing open surgery (OSD group).Results Operation time,intraoperative blood loss,intraoperative blood infusion,time of postoperative abdominal drainage-tube removal,time of gastrointestinal function recovery and duration of hospital stay were respectively (150 ± 37) min,(223 ± 129) ml,(91 ± 138) ml,(4.0 ± 1.0)d,(33 ±9)h,(5.6 ± 1.0)d in the LSD group,(183 ±42) min,(346 ± 131) ml,(214 ± 182) ml,(5.5 ± 1.3)d,(42 ± 14)h,(7.5 ± 1.4)d in the OSD group,with statistically significant differences between groups(t =-2.203,-4.980,-2.830,-5.553,-2.307,-6.635,all P ＜ 0.05).The main complications included pancreatic fistula,intra-abdominal bleeding,intra-abdominal infection,pulmonary infection,refractory ascites,portal vein system thrombosis and incision infection,and there were respectively 0,1,2,2,3,13,0 in the LSD group and 3,4,6,6,7,14,3 in the OSD group,with statistically significant differences between groups (x2 =5.872,4.792,6.179,6.179,6.010,4.335,5.872,all P ＜ 0.05).All the 205 patients received follow-up for a median time of 38 months (12-72 months).Gastroscopy showed improvement of esophageal and gastric varices in postoperative 6 months.Conclusion Laparoscopic splenectomy and pericardial devascularization for the treatment of portal hypertension is safe,feasible and effective.

Objective To investigate the expressiorn of microRNA-622(miR-622) and dual specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) in colon cancer tissues and cell lines and explore the effect of miR-622 on SW11l6 cells migration and invasion.Methods Eighty-two colon cancer tissues and paired para-tumor tissue specimens were collected.C.olon cancer cell line SW1116,SW480 and normal human colon epithelial cell line NCM460 were cultured.MiR-622 was detected by using Real time PCR,DYRK2 expression was measured by using immunohistochemistry,Real time PCR anid Western blot in tissue level and cell level,respectively.The relation of miR-622 and DYRK2 was analyzed by Pearson correlation analysis.miR-622 mimics transfection was conducted to up-regulate miR-622,while negative control,NC group were transfected with control sequence.Expression of DYRK2 was evaluated by using Real time PCR and Western blot,while Transwell chamber assays were used to assess the migration ability changes.Results Real time PCR and Western blot results showed that miR-622 mRNA was highly expressed in colorectal cancer tissue and colon cancer cell SW1116,whereas DYRK2 mRNA and protein were lowly expressed when compared with paracancerous tissue and normal colonic epithelial cell line NCM460.An obvious negative correlation was showed between miR-622 and DYRK2(r=0.916,P＜0.01).Compared to NC group,DYRK2 mRNA and protein expression were down-regulated after transfection of miR-622 mimics,which was observerd through Real time PCR and Western blot(P＜0.01).Correspondingly,compared to NC group,the migration ability of SW116 was remarkably enhanced after transfection of miR-622 mimics(P＜0.01).Conclusion The expression of miR-622 is high and DYRK2 is low in colon cancer.Up-regulation of miR-622 could negatively regulate DYRK2 expression and promote SW1116 cells migration.

OBJECTIVE:To optimize formulation matrix of processed Aconitum carmichaelii hydrogel patch,and to investigate its in vitro drug release.METHODS:The ratio of NP700,dihydroxyaluminum aminoacetate,tartaric acid and PVP K90 in processed A.carmichaelii hydrogel patch matrix was optimized by central composite design-response surface method (CCD-RSM) with initial adhesion,peel strength and sensory evaluation as evaluation indexes.The modified Franz diffusion cell method was used for in vitro drug release test processed A.carmichaelii hydrogel patch using accumulative release amount of six ester type alkaloids benzene [benzoyl mesaconine (BM),benzoyl aconitum (BA),benzoylhy paconine (BH),mesaconitine (MT),hypaconitine (HT) and aconitine (AT)] as evaluation indexes.RESULTS:The optimal matrix formulation was NP700-dihydroxyaluminum aminoacetate-tartaric acid-PVP K90 (1.72 ∶ 0.10 ∶ 0.02 ∶ 1.65,m/m/m/m).In validation test,the contents of six ester type alkaloids were 52.77,28.52,28.78,8.81,8.75,8.21 μg/g(RSD＜5％,n=3),comprehensive score was 118.67 ± 1.33 (RSD=4.62％,n=3).The release behavior of BM in vitro conformed to the Higuchi equation.The release behaviors of other 5 alkaloids were consistent with the Higuchi equation.12 h accumulative release amounts of BM,BA,BH,MT,HT and AT were 12.04,2.95,3.55,2.64,2.48,1.97 μg/cm2,respectively.CONCLUSIONS:The processed A.carmichaelii hydrogei patch prepared by matrix prescription is good in appearance,adhesion and in vitro release.The research can provide a basis for the development of new dosage form of processed A.carmichaelii.

Objective To investigate the causes and treatments for the congestion after pig-tail catheter drainage of liver abscess.Methods Clinical data of 3 patients with complicated liver abscess admitted to Tangdu Hospital of Air Force Military Medical University from April 2016 to January 2017 were retrospectively analyzed.The informed consents of all patients were obtained and the local ethical committee approval was received.Case 1,male,aged 84 years;Case 2,female,aged 57 years;Case 3,female,50 years.The pig-tail catheter was clogged after being placed in 3 patients for drainage and the drainage catheters were therefore rotated clockwise or counter clockwise.Results After multiple rotations,the head end of drainage catheter was loosened and unclogged and necrotic tissues was drained out.Mild or moderate fever was observed in cases 1 and 3 after rotating the pig-tail catheter,which was relieved spontaneously.3 patients presented with mild bleeding after rotating the catheter and no significant change was noted in Hb.After the drainage catheter was unobstructed,the fever was relieved and all were cured and discharged.No recurrence was observed at postoperative 1 year.Conclusions For the intractable congestion of pig-tail catheter in liver abscess patients,rotating and loosening the catheter can be a good appoach.