Mevalonic aciduria is a rare early-onset cholesterol biosynthesis disorder，inherited in an autosomal recessive manner，which characterized with recurrent fever，hepatosplenomegaly，lymphadeno-pathy，vomiting，diarrhea and neurological damage symptoms. The symptoms of mevalonic aciduria could appear at any stage throughout the whole life cycle，and the youngest case has been diagnosed in the neonatal period. Lacking of specific clinical manifestations，it is easy to be confused with other diseases in real clinical settings. It is important that increasing awareness of this disease could effectively decrease misdiagnosis and delayed diagnosis. This paper introduces the advance of mevalonic aciduria from the aspects of genetic variants，clinical manifestations and neuroimaging changes，to help clinicians better identify and diagnose at an early stage.

Objective To systematically compare the efficacy of different virtual reality(VR)technologies on motor dysfunction in patients with Parkinson's disease(PD)through a network meta-analysis(NMA).Methods Following the PRISMA-NMA guidelines,randomized controlled trials(RCT)that compared the effect of at least two interventions on motor function in patients with PD were searched in PubMed,Embase,Cochrane Li-brary,Web of Science,CNKI,Wanfang data and VIP.The interventions included immersive virtual reality(IVR),non-immersive virtual reality(VRT),augmented reality(AR),treatment as usual(TAU)and active control(AC).The primary outcomes included Unified Parkinson's Disease Rating Scale Part Ⅲ(UPDRS-Ⅲ),Berg Balance Scale(BBS)and Timed Up and Go Test(TUGT).A frequentist-based random-effects model was used to conduct NMA,and the surface under the cumulative ranking curve(SUCRA)was used to rank the interventions.Results A total of 20 RCT involving 890 patients were included.IVR performed best in improving the score of UPDRS-Ⅲ(SUCRA=97.7%)and was significantly superior to TAU(SMD=-0.82,95%CI-1.28 to-0.37).IVR showed the highest probability of being the best option for the score of BBS(SUCRA=85.2%)and was signifi-cantly superior to TAU(SMD=3.94,95%CI 1.08 to 6.80).IVR performed best in the outcome of TUGT(SU-CRA=95.1%)and was significantly superior to VRT(SMD=1.06,95%CI 0.40 to 1.72),AR(SMD=-1.09,95%CI-1.98 to-0.19)and TAU(SMD=-1.38,95%CI-1.95 to-0.82).However,subgroup analysis revealed that the efficacy advantage of IVR was mainly confirmed in short-term(four to six weeks)interventions,while the evidence for long-term efficacy was currently very limited.Conclusion The efficacy of interventions on motor rehabilitation in patients with PD appears to be positively correlated with the technology's level of immersion.As the most immersive technology,IVR is the optimal choice for im-proving overall motor function,balance and mobility in patients with PD.VRT and AR serve as effective adju-vants and are superior to TAU.

Objective To systematically compare the efficacy of different virtual reality(VR)technologies on motor dysfunction in patients with Parkinson's disease(PD)through a network meta-analysis(NMA).Methods Following the PRISMA-NMA guidelines,randomized controlled trials(RCT)that compared the effect of at least two interventions on motor function in patients with PD were searched in PubMed,Embase,Cochrane Li-brary,Web of Science,CNKI,Wanfang data and VIP.The interventions included immersive virtual reality(IVR),non-immersive virtual reality(VRT),augmented reality(AR),treatment as usual(TAU)and active control(AC).The primary outcomes included Unified Parkinson's Disease Rating Scale Part Ⅲ(UPDRS-Ⅲ),Berg Balance Scale(BBS)and Timed Up and Go Test(TUGT).A frequentist-based random-effects model was used to conduct NMA,and the surface under the cumulative ranking curve(SUCRA)was used to rank the interventions.Results A total of 20 RCT involving 890 patients were included.IVR performed best in improving the score of UPDRS-Ⅲ(SUCRA=97.7%)and was significantly superior to TAU(SMD=-0.82,95%CI-1.28 to-0.37).IVR showed the highest probability of being the best option for the score of BBS(SUCRA=85.2%)and was signifi-cantly superior to TAU(SMD=3.94,95%CI 1.08 to 6.80).IVR performed best in the outcome of TUGT(SU-CRA=95.1%)and was significantly superior to VRT(SMD=1.06,95%CI 0.40 to 1.72),AR(SMD=-1.09,95%CI-1.98 to-0.19)and TAU(SMD=-1.38,95%CI-1.95 to-0.82).However,subgroup analysis revealed that the efficacy advantage of IVR was mainly confirmed in short-term(four to six weeks)interventions,while the evidence for long-term efficacy was currently very limited.Conclusion The efficacy of interventions on motor rehabilitation in patients with PD appears to be positively correlated with the technology's level of immersion.As the most immersive technology,IVR is the optimal choice for im-proving overall motor function,balance and mobility in patients with PD.VRT and AR serve as effective adju-vants and are superior to TAU.

Objective:To explore the characteristics of renal oxidative stress injuries in rats with high-voltage electric burns and the intervention effects of breviscapine.Methods:This study was an experimental study. One hundred and sixty 8-10-week-old male Sprague Dawley rats were divided into sham injury group, electric burn group, saline group, low breviscapine group, middle breviscapine group, and high breviscapine group, with 60 rats in each of the sham injury group and electric burn group, 10 rats in each of the other 4 groups, respectively. The rats in sham injury group and electric burn group were divided into 10 rats at each time point, including post injury hour (PIH) 0 (immediately), 8, 24, 48, and 72, and post injury week (PIW) 1. The rats in sham injury group were not conducted with electrical current to cause sham injury. The rats in the other 5 groups were caused high-voltage electric burns. The rats in sham injury group and electric burn group were not treated after injury. The rats in saline group, low breviscapine group, middle breviscapine group, and high breviscapine group were intraperitoneally injected with 5 mL/kg normal saline or 0.4, 1.6, and 4.0 g/L breviscapine, repeated every 24 h until PIH 72. After the model was successfully made, 14 rats died, including 1, 2, 2, and 1 rat (s) at PIH 24, 48, and 72 and PIW 1 in electric burn group, 4, 1, 2, and 1 rat (s) at PIH 72 in saline group, low breviscapine group, middle breviscapine group, and high breviscapine group, respectively. The kidney tissue collected from rats in the 6 groups was weighed and the kidney/body weight ratio was calculated. The left upper pole tissue of kidney was collected from each 4 rats in sham injury group, and in electric burn group at PIH 8, 24, 48, and 72 and PIW 1, and in saline group, low breviscapine group, middle breviscapine group, and high breviscapine group at PIH 72. The renal tubular and renal interstitial injury was evaluated by a semi-quantitative histological scoring system after hematoxylin-eosin staining. The inferior vena cava blood samples were collected from rats in the 6 groups to measure the serum creatinine levels via sarcosine oxidase method, and serum urea nitrogen levels via urease method. The right renal cortices were collected from rats in the 6 groups to measure the catalase (CAT) activity in the supernatant of renal tissue via molybdic acid method, and the levels of advanced oxidation protein product (AOPP) and Klotho protein in the supernatant of renal tissue via enzyme-linked immunosorbent assay.Results:At PIH 8, 48, and 72 and PIW 1, the kidney/body weight ratios of rats in electric burn group were significantly higher than those in sham injury group (with t values of -0.52, -3.75, -4.05, and -2.25, respectively, P<0.05). At PIH 72, compared with those in electric burn group, saline group, low breviscapine group, and middle breviscapine group, the kidney/body weight ratio of rats in high breviscapine group was significantly decreased (with P values all <0.05). Compared with those in sham injury group, the renal tubular and renal interstitial injury scores of rats in electric burn group at PIH 48 and 72 and PIW 1 were significantly increased ( P<0.05). Compared with those in electric burn group at PIH 8 and 24, the renal tubular and renal interstitial injury score of rats in electric burn group at PIW 1 was significantly increased (with P values all <0.05). At PIH 72, the renal tubular and renal interstitial injury scores of rats in the 5 groups of rats with electric burns were similar ( P>0.05). At PIH 8, 24, 48, and 72 and PIW 1, the levels of serum creatinine and serum urea nitrogen of rats in electric burn group were significantly higher than those in sham injury group (with Z values of -2.00, -2.37, -2.62, -2.67, -3.67, -2.34, -3.11, -3.43, -3.11, and -3.51, respectively, P<0.05). Compared with that in electric burn group at PIH 0, the levels of serum creatinine of rats in electric burn group at PIH 72 and PIW 1 were significantly increased ( P<0.05). Compared with that in electric burn group at PIH 8, the levels of serum creatinine of rats in electric burn group at PIH 72 and PIW 1 were significantly increased ( P<0.05). Compared with that in electric burn group at PIH 24, the level of serum creatinine of rats in electric burn group at PIW 1 was significantly increased ( P<0.05). At PIH 72, the levels of serum creatinine of rats in the 5 groups of rats with electric burns were similar ( P>0.05). Compared with that in electric burn group, the levels of serum urea nitrogen of rats in low breviscapine group, middle breviscapine group, and high breviscapine group were significantly decreased ( P<0.05). Compared with that in saline group, the levels of serum urea nitrogen in middle breviscapine group and high breviscapine group were significantly decreased ( P<0.05). At PIH 48 and 72 and PIW 1, the CAT activities in the supernatant of renal tissue of rats in electric burn group were significantly lower than those in sham injury group (with Z values of -2.22, -2.13, and -3.51, respectively, P<0.05). At PIH 8, 24, 48, and 72 and PIW 1, the levels of AOPP in the supernatant of renal tissue of rats in electric burn group were significantly higher than those in sham injury group (with Z values of -2.00, -3.15, -2.71, -2.04, and -2.33, respectively, P<0.05). At PIH 0-PIW 1, the levels of Klotho protein in the supernatant of renal tissue of rats in sham injury group and electric burn group were all similar ( P>0.05). Compared with that in electric burn group at PIH 0, the CAT activities in the supernatant of renal tissue of rats in electric burn group at PIH 72 and PIW 1 and the levels of Klotho protein in the supernatant of renal tissue of rats in electric burn group at PIH 48 and 72 and PIW 1 were significantly decreased ( P<0.05). Compared with that in electric burn group at PIH 8, the CAT activities in the supernatant of renal tissue of rats in electric burn group at PIH 72 and PIW 1 and the levels of Klotho protein in the supernatant of renal tissue of rats in electric burn group at PIH 48 and 72 and PIW 1 were significantly decreased ( P<0.05). Compared with that in electric burn group at PIH 24, the CAT activities in the supernatant of renal tissue of rats in electric burn group at PIH 72 and PIW 1 were significantly decreased ( P<0.05). Compared with that in electric burn group at PIH 48, the CAT activity in the supernatant of renal tissue of rats in electric burn group at PIW 1 was significantly decreased ( P<0.05). At PIH 72, the levels of Klotho protein in the supernatant of renal tissue of rats in the 5 groups of rats with electric burns were similar ( P<0.05). Compared with 14.6 (12.6, 23.6) U/mgprot in electric burn group, the CAT activities in the supernatant of renal tissue of rats in low breviscapine group (20.5 (18.0, 39.8) U/mgprot), middle breviscapine group (24.9 (14.7, 28.9) U/mgprot), and high breviscapine group (28.0 (21.9, 39.1) U/mgprot) were significantly increased ( P<0.05). Compared with 15.7 (13.7, 25.6) U/mgprot in saline group, the CAT activities in the supernatant of renal tissue of rats in middle breviscapine group and high breviscapine group were significantly increased ( P<0.05). Compared with that in low breviscapine group, the CAT activity in the supernatant of renal tissue of rats in high breviscapine group was significantly increased ( P<0.05). Compared with those in electric burn group and saline group, the levels of AOPP in the supernatant of renal tissue of rats in middle breviscapine group and high breviscapine group were significantly decreased ( P<0.05). Conclusions:After high-voltage electric burns, oxidative stress injury occur in the kidneys of rats, which is aggravated with time extension. Breviscapine can alleviate oxidative stress injuries in the kidneys of rats with high-voltage electric burns.

Objective:To summarize the imaging presentations of the fallopian canal cerebrospinal fluid leaking (FCCFL).Methods:The high resolution CT (HRCT)and MRI materials of 4 patients (4 ears) with FCCFL confirmed by surgery between August 2016 to November 2023 were retrospectively analyzed. Among these, there were 2 males and 2 females, their ages ranged from 6 to 69 years.Results:All of the FCCFL were unilateral, including 2 on the left and 2 on the right.Clinically, the patients with FCCFL suffered from clear nasal fluid flow, ear tightness, and hearing loss. On CT, all of the affected ears were depicted markedly dilatation of the proximal portion of fallopian canal(FC), the labyrinthine segment and geniculate fossa were involved in 4 cases, and involvement of tympanic segment in 1 case at the same time. The geniculate fossa in the affected side were significantly enlarged, protruding upwards into the tympanic cavity, with one case simultaneously involving the cochlea. On MRI, the hyposignal on T 1WI and hypersignal on T 2WI or water sequence like cerebrospinal fluid (CSF) were shown in the enlargement FC, without diffusion restriction, and non-enhancing with administration Gadolinium contrast.CSF-like signal effusion was shown in all of the affected tympanum, of which, the CSF-like signal effusion was demonstrated in the area along the superficial petrosal nerve, the right pterygopalatine fossa and the parapharyngeal space. The adjacent intracranial meninges were presented thickening in 3 cases. Conclusion:The imaging appearances of FCCFL present some characteristics:on HRCT, the proximal portions of the affected FC depicts markedly enlargement,especially the geniculate fossa.While they present CSF-like signal, no diffusion restriction, and no enhancement administration, Gadolinium contrast on MRI, accompanying the CSF-like signal effusion in the affected tympanum.

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 summarize the best evidence of exercise management of tumor-associated sarcopenia and provide reference for medical personnel to formulate individualized exercise intervention plans.Methods:BMJ Best Practice, UpToDate, Cochrane Library, Embase, PubMed, CINAHL, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang database, National Guideline Clearinghouse, Scottish Intercollegiate Guidelines Network, and other databases were searched by computer for literature on exercise intervention for patients with tumor-associated sarcopenia, including clinical decision making, guidelines, expert consensus, evidence summary and systematic reviews. The search period was from the establishment of the databases to April 23, 2023. Two researchers independently conducted literature quality evaluation, evidence extraction, and integration.Results:A total of 12 articles were included, including 4 guidelines, 3 expert consensus papers, and 5 systematic reviews. A total of 32 pieces of evidence were summarized from five aspects, including exercise evaluation, exercise timing, exercise plan, exercise management, and evaluation indicators.Conclusions:This study summarizes the best evidence for exercise intervention in patients with tumor-associated sarcopenia and suggestes that medical staff should apply the proof according to the clinical context and the patient's wishes.

This paper discussed how to set the limit of impurities in the quality standard when the impurities in small-molecular innovative drugs were metabolites.Firstly,through the analysis and interpretation of each relevant guideline,in combination with the review cases of FDA and EMA,found out the conditions for qualification of im-purity,and then establ ish the acceptable limit of impurities based on the test results of multiple batches,the incre-ments of production process and storage process.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To develop and verify a predictive model for hip fracture risk in the aged patients with knee osteoarthritis (KOA) on the basis of analysis of the risk factors associated with the hip fracture.Methods:A retrospective study was conducted to analyze the 701 patients who had been diagnosed with KOA (Kellgren-Lawrence grades 1 to 4) at Dongyang Hospital affiliated to Wenzhou Medical University from September 2013 to September 2023. The cohort consisted of 275 males and 426 females with an age of (76.5±8.4) years. The patients were divided into a fracture group ( n=145) and a fracture-free group ( n=556) based on whether a hip fracture occurred during the follow-up period. The 2 groups were compared in terms of age, gender, comorbidities, albumin level, absolute lymphocyte count, and Kellgren-Lawrence grade, etc. The items with P<0.05 were analyzed by a multivariate logistic regression model to identify the risk factors for hip fracture in the aged KOA patients. A clinical prediction model based on the above risk factors was constructed and validated for hip fracture risk in the aged KOA patients. Results:Multivariate logistic regression analysis identified the following as independent risk factors for hip fracture in the aged KOA patients: female ( OR=2.009, 95% CI: 1.280 to 3.154, P=0.002), age ≥75 years ( OR=2.313, 95% CI: 1.493 to 3.583, P=0.001), Kellgren-Lawrence grades of 3-4 ( OR=2.348, 95% CI: 1.533 to 3.596, P=0.001), an albumin level <35 g/L ( OR=0.316, 95% CI: 0.191 to 0.522, P=0.001), and an absolute lymphocyte count <0.8×10 9/L ( OR=0.133, 95% CI: 0.069 to 0.253, P=0.001). The area under the ROC curve (AUC) for the model developed by this study was 0.753 in the training set and 0.815 in the validation set ( P<0.05). The Hosmer-Lemeshow goodness-of-fit test showed that the consistency between the predicted risk and the actual risk was good in the training and validation sets ( P<0.05). The calibration curves for both the training and validation sets closely aligned with the ideal curve. The clinical decision curve analysis showed that the nomogram model had a good net benefit rate and a good predictive potential. Conclusions:Female, age ≥75 years, Kellgren-Lawrence grades of 3-4, an albumin level <35 g/L, and an absolute lymphocyte count <0.8×10 9/L are independent risk factors for hip fracture in the aged KOA patients. Since the nomogram prediction model based on these risk factors is satisfactory in discrimination and calibration, it shows a certain predictive ability and application value in clinic.