OBJECTIVE To evaluate the efficacy and safety of rituximab （RTX） in the treatment of primary Sjögren syndrome （pSS）. METHODS Randomized controlled trials （RCTs） on the effects of RTX （trial group） versus placebo （control group） in the treatment of pSS were searched from the Cochran Library， PubMed， Embase， Medline， Web of Science， VIP， CNKI， Wanfang， and other databases during the inception to February 2024. After literature screening and quality evaluation， meta-analysis was performed by using RevMan 5.3 software. RESULTS Seven RCTs were finally included， involving a total of 518 patients. Results of meta-analysis showed that European League Against Rheumatism Sjögren syndrome disease activity index （ESSDAI） score [MD＝－1.17， 95%CI（－1.52， －0.82）， P＜0.000 01] and oral dryness visual analogue scale （VAS） score [MD＝－3.97， 95%CI （－5.08， －2.86）， P＜0.000 01] in the trial group were significantly lower than the control group； unstimulated salivary flow rate [SMD＝0.64， 95%CI（0.41， 0.87）， P＜0.000 01] and Schirmer score [MD＝0.19， 95%CI（0.18， 0.20）， P＜0.000 01] were significantly higher than the control group. There was no statistical significance in response rate [RD＝0.10， 95%CI（－0.04， 0.23）， P＝0.16]， fatigue VAS score [MD＝－12.50， 95%CI（－35.14， 10.15）， P＝0.28]， European League Against Rheumatism Sjögren syndrome patient reported index （ESSPRI） score [MD＝0.33， 95%CI（－0.53， 1.18）， P＝0.46]， Short-form 36 health survey physical component summary （SF36-PCS） score [MD＝0.90， 95%CI（－2.97， 4.78）， P＝0.65]， SF-36 mental component summary （SF36-MCS） score [MD＝0.11， 95%CI（－0.41， 0.63）， P＝0.68]， total salivary gland ultrasound score [SMD＝－1.91， 95%CI（－4.01， 0.19）， P＝0.07] or the incidence of adverse drug reactions [OR＝1.15，95%CI（0.62，2.13），P＝0.66] between 2 groups. CONCLUSIONS RTX has advantages in the improvement of ESSDAI score， unstimulated salivary flow rate， Schirmer score and oral dryness VAS score in pSS patients， and has a good safety profile. However， it did not exhibit significant improvement in fatigue VAS score， ESSPRI score， SF36-PCS score， SF36-MCS score or response rates.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Enteral nutrition plays an irreplaceable role in the nutritional treatment of critically ill patients. In order to help clinical medical staff to manage the common complications during the implementations of enteral nutrition for critically ill patients, the consensus writing team carried out literature retrieval, literature quality evaluation, evidence synthesis. Several topics such as diarrhea, aspiration, high gastric residual volume, abdominal distension, etc. were assessed by evidence-based methodology and Delphi method. After two rounds of expert investigations, Expert consensus on prevention and management of enteral nutrition therapy complications for critically ill patients in China (2021 edition) developed, and provided guidance for clinical medical staff.

Objective To investigate the susceptibility profile of clinical isolates in the First Affiliated Hospital of Guangzhou Medical University during 2015-2017. Methods Susceptibility test was carried out using Kirby-Bauer method or automated systems. Results were analyzed according to CLSI 2017 breakpoints. Results A total of 17 645 clinical isolates were isolated from January 2015 to December 2017, including 3 091(17.5％)gram positive and 14 554(82.5％)gram negative bacteria. Methicillinresistant S. aureus(MRSA)and coagulase-negative Staphylococcus(MRCNS)accounted for 50.7％ and 77.9％, respectively. No staphylococcal isolates were found resistant to vancomycin, teicoplanin or linezolid. E. faecalis strains showed much lower resistance rate to most drugs tested than E. faecium. Nine(0.8％)E. faecalis isolates were found resistant to vancomycin. A total of 227 strains of the non-meningitis S. pneumoniae were tested, 44.1％ of which were isolated from adults and 55.9％ from children. Most of the S. pneumoniae isolated from adults and children were susceptible to penicillin(88.0％ and 81.1％, respectively). E. coli showed the highest proportion in three years. ESBLs were produced in 53.3％ of E. coli and 28.5％ of Klebsiella spp. A total of 255 strains of carbapenem-resistant Enterobacteriaceae(3.7％), 665 strains of carbapenem-resistant Pseudomonas aeruginosa(26.2％)and 900 strains of carbapenem-resistant Acinetobacter baumannii(57.5％)were identified. The annual change of prevalence was insignificant. A total of 141 strains of extensively-drug resistant Pseudomonas aeruginosa(5.6％)and 458 strains of extensively-drug resistant A. baumannii(29.3％)were identified, showing decreasing prevalence from 2015 to 2017. Conclusions The bacterial resistance in this hospital is relatively stable in the past three years, but it is still necessary to strengthen hospital infection control and management, and maintain good practice in surveillance of bacterial resistance.

Objective To explore the clinical efficacy of decitabine combined with HAG or HAG-like regimen for newly diagnosed and relapsed/refractory acute myeloid leukemia (AML) patients.Methods Thirty-one newly diagnosed (18 cases) and relapsed/refractory (13 cases) AML patients receiving decitabine combined with HAG or HAG-like regimen in Yinzhou Hospital Affiliated to Medical School of Ningbo University from January 2014 to December 2017 were analyzed retrospectively.Results The outcome of 18 newly diagnosed AML patients showed that the overall response rate (ORR) was 77.8 ％ (14/18),including 13 patients achieved complete response (CR) / CR with incomplete blood count recovery (CRi),and the 1-year overall survival (OS) rate was 39.2 ％,the l-year disease free survival (DFS) rate was 32.5 ％.The outcome of 13 relapsed/refractory AML patients showed that the ORR was 53.8 ％ (7/13),including 6 patients achieved CR/CRi,and the 1-year OS rate was 22.4 ％,the 1-year DFS rate was 7.7 ％.Eleven patients were transformed from myelodysplastic syndromes (MDS),the ORR was 90.9 ％ (10/11),including 9 patients achieved CR/CRi,and the 1-year OS and DFS rates were 63.8 ％ and 37.5 ％ respectively.The main adverse events of infection and bleeding were caused by myelosuppression,and non-hematological toxicity included gastrointestinal and liver dysfunction.After the anti-infection and supportive treatment,all 31 patients were safely through bone marrow suppression,with no treatment-related deaths.Conclusions Decitabine combined with HAG or HAG-like regimen is an effective and safe treatment strategy for hypoplastic newly diagnosed and relapsed/refractory AML patients.It is produced relatively higher curative effect for AML patients with MDS transformation.

Objective To investigate the training expectations and training strategies of orthopedic clinical specialist nurses (OCSN).Methods Totally 5 020 orthopedic nurses from 342 hospitals from 30 provinces and cities were selected bv convenience sampling.Participants were investigated hy WeChat platform with self-designed questionnaire.Results A total of 4 982 effective questionnaires were collected.Among investigated nurses,13.7％ of them received orthopedic specialist nurses training;91.4％ believed that training should be carried out.Qualifications should be:college degree and above,senior nurse and above,at least 3 ～5 years of nursing experience,1～3 years of nursing experience in orthopedic department.For curriculum,public courses expected to be arranged were communieation skills,nursing teaching,nursing management,and nursing research;expected professional courses were functional exercises,pain management,extremity injury nursing,common treatment techniques in orthopedic department,traction nursing,and position nursing.It was suggested that training was divided into subspecialties and off-duty;classroom teaching,teaching rounds,case discussion and experience exchange were expected training methods;"theory-practice-theory-practice" was most preferable traiuing mode.The preferred teachers were orthopedic doctors,orthopedic head nurses,orthopedic specialist nurses,and senior orthopedic nurses.The length of training was expected to be three months,time for clinical practice should be greater than or equal to theoretical teaching,and the practice bases should be tertiary hospitals.Evaluation should be performed before completion,recertification could be later than completion,and the interval time of recertification should be within 5 years.Conclusion Training needs of orthopedic nurses for OCSN are strong.Training expectations(contents,length,modes and teachers) of orthopedic nurses should be considered when designing systematic training program on OCSN.

Objective To evaluate the effect of electroconvulsive therapy (ECT) on the expression of phosphorylated glutamate receptor 1 (p-GluR1) and Ca2+/calmodulin-dependent protein kinase Ⅱ α (p-CaMK Ⅱ α) under small dose ketamine combined with propofol anesthesia in the depressed rats.Methods Forty healthy adult male Sprague-Dawley rats,weighing 200-250 g,aged 2-3 months,were used in this study.Mental depression was induced by exposing the animals to chronic unpredictable mild stress (CUMS).Forty mentally depressed rats were divided randomly into 5 groups (n =8 each) using a random number table:M0-4 groups.Propofol 80 mg/kg and ketamine 10 mg/kg were injected intraperitoneally in M0-4 groups.After disappearance of righting reflex,M1-4 groups received ECT of 60,120,180 and 240 mC once a day for 7 consecutive days,respectively,by means of a current (frequency 50 Hz,sine-wave,pulse width 0.7 ms,1-s duration) delivered via ear-clip electrodes,while group M0 received ECT of no quantity of electric charge via ear-clip electrodes.Before CUMS,at 1 day after CUMS and at 1 day after ECT,sucrose preference test was applied to evaluate the depressive behavior.The sucrose preference percentage (SPP) was calculated.At 4 days after CUMS and 4 days after ECT,the learning and memory function was assessed using Morris water maze test.The rats were then sacrificed,and hippocampi were isolated to detect the expression of GluR1,p-GluRl,CaMK Ⅱ α and p-CaMK Ⅱ α by Western blot.Results The SPP was significantly lower after CUMS than before CUMS in M0-4 groups (P＜0.05).Compared with that after CUMS,the SPP was significantly increased,the escape latency was shortened,and the space exploration time was prolonged after ECT in M1-4 groups (P＜0.05).There was no significant difference in SPP after ECT between M1-4 groups (P＞0.05).Compared with group M0,the SPP was significantly increased,and the expression of pGluR1 and p-CaMK Ⅱ α was up-regulated in M1-4groups (P＜0.05).Compared with group M2,the escape latency was significantly prolonged,the space exploration time was shortened,and the expression of pGluR1 and p-CaMK Ⅱ α was down-regulated after ECT in the other groups (P＜0.05).There was no significant difference in GluR1 and CaMK Ⅱ α expression after ECT between the five groups (P＞ 0.05).Conclusion ECT can induce cognitive decline when applied for anti-depression under small dose ketamine combined with propofol anesthesia,and the mechanism is related to increased phosphorylation of GluR1 and CaMK Ⅱ α expression in rats.

Objective To explore the effect of low-dose ketamine combined with propofol anesthesia on expres?sion of glutamine receptor subunit 1 (GluR1) and 2 (GluR2) in the hippocampus of depressed rats after electroconvulsive therapy. Methods Healthy adult male Sprague-Dawley rats, weighing 200~250 g, were used in this study. Mental depres?sion was induced by chronic unpredictable mild stress. Thirty-two depressed rats were randomly divided into 4 groups (n=8): metal depression group (group A), ECT group (group B), ECT+propofol group (group C) and ECT+propofol+ket?amine group (group D). Eight normal rats served as control group. Control group received no treatment. Group A received intraperitoneal injection of normal saline 8 mL/kg plus sham ECT. Group B, C and D received ECT once a day for 7 con?secutive days following intraperitoneal injection of normal saline 8 mL/kg, propofol 80 mg/kg and propofol 80 mg/kg +ketamine 10mg/kg, respectively. Sucrose preference test and Morris water maze were performed to assess depressed be?havior and learning and memory function, respectively. RT-PCR and Western-blot assay were used to detect the expres?sion of GluR1 , GluR2 and their mRNA expression. Results After ECT, compared with control group and group A, changes of SPP in group B, C and D were obvious. The change of SPP in group D was much higher than all other groups (P<0.05). Rats in group B showed prolonged escape latency and shortened space exploration time, which were significantly different from all other groups (P<0.05). Rats in group D showed the most shortened escape latency and prolonged space exploration time (P<0.05). The expression of GluR1 was significantly increased in group B, C and D compared with group A (P<0.05). The expression of GluR2 and mRNA was significantly decreased in group B and C (P<0.05). The difference in GluR2 and mRNA expression was not significant among group A, D and control group (P>0.05). Conclusion Low-dose ketamine combined with propofol anesthesia exert effective antidepressive action and improve learning and memory function of depressed rats after electroconvulsive therapy. The beneficial effects of the ketamine combined with propofol anesthesia may be related to up-regulation expression of GluR1 and GluR2 in hippocampus.

OBJECTIVETo evaluate the efficacy of continuous femoral block on the postoperative analgesia and functional recovery after total knee arthroplasty (TKA).

METHODSTwo hundreds and eighty patients who underwent TKA were randomized into two groups:the group receiving continuous femoral block (CFNB) and the group receiving patient controlled intravenous analgesia (PCIA), each group included 140 participants. Femoral nerve block with ropivacaine by ultrasonic guidance was performed in group CFNB and group PCIA were administrated with patient controlled intravenous analgesia. Numerical rating scale (NRS) scores at rest and in motion at 24, 48, 72 h, 3, 6 and 12 months postoperatively, also the NRS scores at hospital discharge were recorded. The incidence of moderate-severity pain, as well as the degree of knee flexion and the WOMAC scores at 3, 6 and 12 months after surgery were analyzed. The rescue analgesic administration and analgesia-related adverse effects were also recorded. Data were expressed as mean± standard deviation (SD) for normally distributed continuous variables and total number (percent frequency) for categorical variables. If non-normally distributed, data were expressed median inter-quartile range. Student's t-test, Wilcoxon rank test were used to compare results for continuous variables, when appropriate. Chi-square test was used to compare results for categorical variable, Fisher exact test was used for categorical variables when the number of event was less than 5.

RESULTSNRS scores of group CFNB in motion was 3 (3-4) at discharge time, and 3 (2-4), 3 (2-3) at 3 months and 6 months postoperatively, while the scores of group PCIA was 4 (4-4), 3 (3-4), 3 (3-4), respectively. And at rest, NRS scores of group CFNB was 3 (2-3), 1 (1-2), 1 (1-1) at discharge time, and 3, 6 months postoperatively. Compared with group PCIA, NRS scores in motion of group CFNB at discharge time (Z=-5.174, P<0.05) and 3 months (Z=2.308, P=0.021), as well as 6 months postoperatively (Z=-2.495, P=0.013), were significantly lower,also for the NRS scores at rest (Z=-2.405, P=0.016; Z=-4.360, P<0.05; Z=-9.268, P<0.05). The degree of knee flexion of group CFNB at 3 and 6 months postoperatively was 92 (88-97), 103 (99-106), while the degree of knee flexion of group PCIA was 89 (86-95), 100 (97-105); the WOMAC scores of group CFNB at 3 and 6 months postoperatively was 21 (18-26), 18 (16-22), while the scores of group PCIA was 24 (20-27), 21 (17-24). WOMAC scores of group CFNB was lower compared with group PCIA at 3 (Z=-2.467, P=0.014) and 6 (Z=-2.537, P=0.011) months postoperatively while the degree of knee flexion of group CFNB was higher (Z=-2.175, P=0.030; Z=-2.471, P=0.013). Moreover, the frequency of bolus and frequency of rescue of group CFNB was 2.3 and 0.6, while the frequency of group PCIA was 2.6 and 1.1, the frequency of bolus and frequency of rescue were lower in group CFNB (t=-2.984, P=0.003; t=-3.213, P=0.002). The incidence of adverse events such muscle weakness of low limbs,nausea and vomiting were similar in two groups (P>0.05).

CONCLUSIONCFNB can alleviate the postoperative pain after TKA with safety, help improving the short-middle-term functions of knee and quality of patients' lives.

Amides ; administration & dosage ; therapeutic use ; Analgesia ; methods ; Analgesia, Patient-Controlled ; Analgesics ; administration & dosage ; therapeutic use ; Arthroplasty, Replacement, Knee ; Femoral Nerve ; Femur ; Humans ; Knee Joint ; Nerve Block ; Pain, Postoperative ; drug therapy ; Postoperative Period ; Recovery of Function