BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Objective : To investigate the role of enhancer of zeste homolog 2(EZH2)-trimethylated lysine 27 of histone H3(H3K27me3) axis in the dedifferentiation of thyroid cancer and its clinical value as a potential target for the treatment of anaplastic thyroid cancer(ATC). Methods : Immunohistochemical SP method was used to detect the expression of EZH2, H3K27me3, paired box gene 8(PAX8), thyroglobulin(TG) and thyroid transcription factor 1(TTF1) in ATC and papillary thyroid carcinoma(PTC) and their adjacent tissues. The relationship between EZH2 and thyroid differentiation markers(PAX8, TTF1, TG) was further analyzed by gene expression omnibus(GEO) database. ATC cell lines 8305C and BHT-101 were culturedin vitro. Real-time reverse transcription PCR(RT-qPCR) was used to detect the expression of thyroid differentiation markers(TTF1, PAX8) mRNA in ATC cell lines treated with EZH2 inhibitor(GSK126), and evaluate the potential therapeutic effect of GSK126in vitro. The effects of GSK126 and BRAF inhibitor vemurafenib on the proliferation of ATC cell lines were observed by cell proliferation assay. Results : The expression of EZH2 in ATC tissues was significantly higher than that in papillary thyroid carcinoma and adjacent tissues(P<0.05). The expression of H3K37me3 in ATC tissues was significantly lower than that in PTC tissues(P<0.05). EZH2 was negatively correlated with PAX8 and TG expression levels, but not with TTF1 expression level.In vitroexperiments, GSK126 could reverse the expression of thyroid differentiation markers PAX8 and TTF1 in ATC cell lines. GSK126 combined with BRAF inhibitor vemurafenib could significantly inhibit the growth of ATC cell lines. Conclusion The EZH2-H3K27me3 axis plays an important role in regulating thyroid specific markers, and the inhibition of EZH2 by small molecular compounds is a promising target for ATC treatment in the future.

Objective To explore the clinical application value of deep learning image reconstruction(DLIR)-based technique for radiation dose reduction with different noise index(NI)in CT-guided percutaneous transthoracic needle biopsy(PTNB).Methods Thirty-two patients undergoing PTNB were selected,and three sets of CT images with NI of 15,30,and 45 sequentially were obtained after adjusting the puncture needle using the scanning parameters of a small range(40 mm),tube voltage 100 kV,and automatic tube cur-rent modulation(ATCM).Group A was 50％weight of adaptive statistical iterative reconstruction-Veo(ASIR-V)scanned with NI 15,and group B and C were the DLIR-high reconstructed images with NI 30 and NI 45 respectively.The CT value and standard devia-tion(SD)value of paraspinal muscles,subcutaneous fat,and arterial vessels were measured at the puncture center point and its upper and lower 10 mm sclices,respectively,and the signal-to-noise ratio(SNR)and the contrast-to-noise ratio(CNR)were also calculated.Then the images were subjectively scored by two physicians,meanwhile the effective dose(ED)among the three groups was com-pared.Results According to the subjective evaluation,the image quality of group A,B,and C all met the clinical requirement for puncture.The SD and SNR of the images in group B were better than those in groups A and C.The SD and SNR of paraspinal mus-cles and sudcutaneous fat were significantly different between groups A and B,and between groups B and C(P＜0.05),however those of paraspinal muscles and subcutaneous fat between groups A and C were not significant.The differences in ED among the three groups were all statistically significant(P＜0.05).Compared with group A,the ED in groups B and C were reduced by 82.86％and 93.90％respectively,and the ED in group C was reduced by 64.44％compared with group B.Conclusion Increasing the NI combined with the DLIR technique can significantly reduce the radi-ation dose during CT-guided PTNB.

Objective:To compare the clinical outcomes of anterolateral femoral interregional flap with turbocharge technique and traditional anterolateral femoral flap in repair of large limb wounds.Methods:Clinical data of 38 patients with large limb surface wound(11 cm×39 cm-16 cm×65 cm)admitted to the Sir Run Run Shaw Hospital,Zhejiang University School of Medicine from May 2018 to May 2022 were retrospectively analyzed.Eighteen patients were treated by anterolateral thigh perforator flap combined with superficial circumflex iliac artery flap(ALTP-SCIAP)with turbocharge technique(interregional flap group);while 20 patients were treated with unilateral or bilateral anterolateral femoral flaps,combined with skin grafting if necessary(traditional anterolateral femoral flap group).The survival of skin flap,repair of donor area,complications and patient satisfaction were compared between the two groups.Results:In interregional flap group,18 flaps were harvested and transplanted,the flap width,length and the viable area were(9.9±2.0)cm,(44.2±3.5)cm and(343.2±79.9)cm2,respectively.In traditional anterolateral femoral flap group,29 flaps were harvested and transplanted,the flap width,length and the viable area were(11.0±2.8)cm,(21.7±3.2)cm and(186.4±49.2)cm2,respectively.There were significant differences in the flap length and the viable area between the two groups(t=22.365 and 8.345,both P<0.05).In the interregional flap group,the donor site of flap was closed by direct suture in 11 flaps,by skin retractor assisted suture in 6 flaps,and by skin grafting in one flap.In traditional anterolateral femoral flap group,the donor site of flap was closed by direct suture in 12 flaps,by skin retractor assisted suture in 11 flaps,and by skin grafting in 6 flaps.The skin graft rates of the two groups were 5.6%(1/18)and 20.7%(6/29),respectively(χ2=2.007,P>0.05).The interregional flap group had lower postoperative complications rate(5.6%vs.35.0%,χ2=4.942,P<0.05)and higher patient satisfaction rate(94.4%vs.70.0%,χ2=4.448,P<0.05)than traditional anterolateral femoral flap group.Conclusion:Compared with the traditional anterolateral femoral flap,the anterolateral femoral interregional flap with turbocharge technique has a larger flap area,most of the donor areas of the flap can be sutured directly without skin grafting and with less complications and a higher patient satisfaction rate.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To explore the clinical efficacy of prone position ventilation(PPV)in improving hypoxemia in patients with severe brain damage.Methods A retrospective research method was conducted,140 patients with severe brain damage who were admitted to the department of critical care medicine of the First Affiliated Hospital,Zhejiang University School of Medicine from August 2020 to August 2021 were selected as subject objected.According to the inclusion and exclusion criteria,20 patients with oxygenation index≤200 mmHg(1 mmHg≈0.133 kPa)who were treated with PPV were statistically analyzed.The patients'blood gas analysis related indicators[including arterial partial pressure of oxygen(PaO2),fractional of inspired oxygen(FiO2),oxygenation index,arterial oxygen saturation(SaO2),arterial partial pressure of carbon dioxide(PaCO2),pH value],ventilator-related parameters[including peak inspiratory pressure(PIP),positive end-expiratory pressure(PEEP),tidal volume(VT),lung dynamic compliance(Cdyn),etc.],and mean arterial pressure(MAP),heart rate(HR)were compared before PPV,12 hours after PPV,and 12 hours after reverting to supine position.At the same time,the related complications of patients during PPV were recorded.Results There were 15 males and 5 females,the mean age of the patients was(46.10±17.22)years old,the average PPV time was(22.20±5.94)hours.Compared with before PPV,patients showed significant increases in PaO2,oxygenation index,SaO2,VT,and Cdyn at 12 hours after PPV and 12 hours after recovery from supine position[PaO2(mmHg):98.35±21.85,98.45±17.90 vs.72.15±10.14,oxygenation index(mmHg):198.82±40.51,202.27±46.39 vs.133.20±33.95,SaO2:0.97±0.02,0.97±0.01 vs.0.94±0.03,VT(mL):558.42±111.23,580.29±119.44 vs.484.82±123.77,Cdyn(mL/cmH2O):26.11±5.42,27.90±5.80 vs.24.15±6.13,all P<0.05];Compared with 12 hours after PPV,the Cdyn of the patient still showed a significant increase after 12 hours of recovery from supine position(P<0.05).There were no statistical differences in the FiO2,PaCO2,pH value,PIP,PEEP,HR,and MAP of patients at various time points before and after PPV(all P>0.05).Five patients developed redness and swelling at the skin compression site mainly on the face after PPV,which gradually improved after returning to a supine position.During this period,there was no occurrence of catheter detachment,malignant arrhythmia,or significant hemodynamic instability.Conclusion PPV has a certain clinical effect on improving hypoxemia in patients with severe brain damage.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Female pelvic organ prolapse (POP) is caused by damage or loss of pelvic floor support, resulting in displacement of the pelvic organs, which leads to abnormalities in the position and function of the organs, mainly due to damage to the pelvic floor mechanical support structures caused by transvaginal birth, loss of elasticity of the pelvic floor mechanical support structures in old women, and loss of the ability to maintain the pelvic floor. The key to POP surgery is the repair of the apical vagina, but treatment based on this theory has failed to achieve satisfactory clinical outcomes. This article will analyze the common procedures of apical suspension in the treatment of mid-pelvic prolapse from the perspective of pelvic floor morphological features and pelvic floor biomechanics axially.

This paper reports a case of multiple myeloma complicated with Primary systemic light chain amyloidosis peripheral neuropathy.Patient was a male,60 years old with subacute onset of peripheral neuropathy.Patient had previous history of hypertension,coronary heart disease and stable angina pectoris.His urine routine examination 2 months ago showed urine protein(+++).The first clinical symptom with peripheral neuropathy characterized by progressive numbness and weakness of both lower limbs.The diagnosis was made after completing electromyography,lumbar puncture,renal puncture,bone puncture and other related examinations,and relevant treatment was given.As a rare disease of nervous system,the incidence rate is low.Early diagnosis is an important step to reduce mortality and improve prognosis.However,the disease is easily misdiagnosed as diabetic peripheral neuropathy and chronic inflammatory demyelinating polyradiculoneuropathy,thereby delaying diagnosis and treatment.

Objective:To investigate the clinical efficacy of neuroendoscopic hematoma removal versus soft channel drainage in the treatment of chronic subdural hematoma. Methods:The clinical data of 102 patients with chronic subdural hematoma who received treatment in Jincheng People's Hospital from May 2018 to May 2020 were retrospectively analyzed. They were divided into the neuroendoscopy group ( n = 50) and the soft channel group ( n = 52) according to different surgical methods. Perioperative indexes, hematoma clearance rate, China Stroke Scale score, the activity of daily living score, and oxidative stress indexes were compared between the two groups. All patients were followed up for 3 months. The incidence of complications during the follow-up period was calculated. Results:The retention time of the drainage tube in the neuroendoscopy group was shorter than that in the soft channel group [(2.45 ± 0.63) days vs. (3.30 ± 0.78) days, t = 6.06, P < 0.001]. The length of hospital stay in the neuroendoscopy group was shorter than that in the soft channel group [(7.14 ± 1.65) days vs. (9.07 ± 2.11) days, t = 5.15, P < 0.001]. The hematoma clearance rate at postoperative 7 days in the neuroendoscopy group was higher than that in the soft channel group [(93.45 ± 5.50)% vs. (81.86 ± 7.24)%, χ2 = 9.12, P < 0.001]. There were no significant differences in operation time and intraoperative blood loss between the two groups (both P > 0.05). At postoperative 30 days, the China Stroke Scale score in the neuroendoscopy group was lower than that in the soft channel group [(12.74 ± 2.23) points vs. (18.67 ± 2.45) points, t = 12.79, P < 0.001]. The activity of daily life score in the neuroendoscopy group was significantly higher than that in the soft channel group [(77.69 ± 7.11) points vs. (91.35 ± 7.25) points, t = 9.60, P < 0.001]. At postoperative 7 days, glutathione peroxidase level in the neuroendoscopy group was significantly lower than that in the soft channel group [(130.75 ± 13.66) U/L vs. (148.60 ± 14.64) U/L, t = 6.37, P < 0.001]. Malondialdehyde level in the neuroendoscopy group was significantly lower than that in the soft channel group [(5.11 ± 0.65) nmol/L vs. (6.19 ± 0.74) nmol/L, t = 7.83, P < 0.001]. Superoxide dismutase level in the neuroendoscopy group was significantly higher than that in the soft channel group [(275.60 ± 22.33) U/L vs. (254.60 ± 18.55) U/L, t = 5.15, P < 0.001]. There was no significant difference in the incidence of complications between the two groups ( P > 0.05). Conclusion:Compared with soft channel drainage, neuroendoscopic hematoma removal can obtain better short-term curative effects and less oxidative stress response in the treatment of chronic subdural hematoma. Neuroendoscopic hematoma removal does not increase the incidence of postoperative complications and is highly safe.