Objective To observe the effects of dexmedetomidine combined with esketamine on early postoperative pain and cognitive function in elderly patients undergoing spinal surgery.Methods The aged spinal surgery patients were divided into control group and treatment group by random number table method.Both groups were anesthetically induced by intramuscular injection of esketamine 3 mg·kg-1,while the control group was anesthetically induced by intravenous injection of propofol 4 mg·kg-1 with constant velocity pump.The treatment group was given 1 μg·kg-1 dexmedetomidine by intravenous pump for 10 min,and then continued pumping at 0.5 μg·kg-1 rate.The changes of vital signs 5 min before surgery(T1),5 min after surgery(T2),at the end of surgery(T3),at the time of recovery(T4),early postoperative pain,cognitive function,the time of the first patient control analgesia(PC A),the cumulative dosage of sufentanil in different time periods within 48 h and the occurrence of adverse drug reactions were observed in the 2 groups.Results 44 patients were included in the control group and 45 patients in the treatment group,respectively.At T2,T3 and T4,the heart rate of treatment group were(82.51±3.05),(80.15±3.21)and(81.51±3.04)beat·min-1,and that of control group were(92.54±3.10),(93.52±3.05)and(88.45±3.51)beat·min-1,respectively.The mean arterial pressure(MAP)of the treatment group were(54.51±3.58),(55.25±3.21)and(60.25±3.24)mmHg;and that of the control group were(73.25±3.54),(70.52±3.20)and(68.51±3.05)mmHg,respectively.The blood oxygen saturation(SPO2)of treatment groups were(98.56±0.38)％,(98.25±0.35)％and(99.02±0.14)％;and the SPO2 of control group were(94.52±0.35)％,(95.25±0.25)％and(96.25±0.32)％,respectively.Visual analogue pain(VAS)scores were(5.69±1.12),(5.02±0.89),(4.52±0.65)and(4.01±0.45)scores at 2,4,6 and 8 h after operation,respectively;the control group were(6.25±1.35),(5.46±1.12),(4.98±0.84)and(4.25±0.52)scores,respectively.24,36 and 72 h after operation,the scores of MMSE in treatment group were 24.25±1.15,26.25±1.14,27.25±0.89 and 28.86±0.62,respectively;the control group were 22.52±1.02,24.25±1.12,26.58±0.87 and 28.78±0.52,respectively.Compared with the control group,there were statistically significant differences in the above indexes of treatment groups(all P＜0.05).The adverse drug reactions in the control group were mainly lethargy,respiratory depression,nausea and vomiting,and the adverse drug reactions in the treatment group were mainly lethargy,nausea and vomiting,and the incidence of total adverse drug reactions in the treatment group and the control group was 6.67％and 22.73％,respectively,with statistical significance(P＜0.05).Conclusion Dexmedetomidine combined with esketamine is safe and effective in elderly patients undergoing spinal surgery.It can effectively reduce early postoperative pain and quickly restore cognitive function.

Objective To systematically evaluate the clinical efficacy of the prescriptions for softening hardness to dissipate mass combined with Levothyroxine Sodium in the treatment of postoperative thyroid cancer,and to provide evidence-based medical proof for clinical treatment of postoperative thyroid cancer.Methods Computer search was performed in the major domestic and oversea databases for the retrieval of clinical randomized controlled trials(RCTs)of prescriptions for softening hardness to dissipate mass combined with Levothyroxine Sodium for the treatment of postoperative thyroid cancer.After screening the literature according to the inclusion and exclusion criteria,the quality of the included literature was evaluated using the tools for analysis of the bias recommended by Cochrane Reviewer's Handbook and the modified JADAD rating scale,and meta-analysis was performed using RevMan 5.4 software.Results A total of 11 RCTs involving 749 patients were eventually included.The results of meta-analysis showed that compared with Levothyroxine Sodium alone,prescriptions for softening hardness to dissipate mass combined with Levothyroxine Sodium significantly enhanced the efficacy of postoperative patients with thyroid cancer(RR=1.30,95%CI[1.21,1.41],Z = 6.81,P＜0.000 01),and improved the thyroid functions parameters of serum thyroid stimulating hormone(TSH)(SMD=-1.75,95%CI[-2.38,-1.13],Z = 5.47,P＜0.000 01),thyroglobulin(TG)(SMD=-1.13,95%CI[-1.71,-0.55],Z = 3.81,P = 0.000 1),free triiodothyronine(FT3)(SMD=3.42,95%CI[0.73,6.10],Z = 2.50,P = 0.01),free thyroxine(FT4)(SMD=1.85,95%CI[0.05,3.66],Z = 2.02,P = 0.04),and thyroglobulin antibody(TgAb)(SMD=-0.63,95%CI[-1.11,-0.15],Z = 2.55,P = 0.01),increased Karnofsky Performance Status(KPS)scores(SMD= 2.19,95%CI[1.30,3.08],Z = 4.81,P＜0.000 01),shortened the time for the relief of clinical symptoms after thyroid cancer surgery(MD=-4.67,95%CI[-5.38,-3.96],Z = 12.87,P＜0.000 01),reduced the diameter of the largest thyroid nodule after thyroid cancer surgery(MD=-2.51,95%CI[-3.13,-1.89],Z = 7.94,P＜0.000 01),regulated the immune function indicators of T lymphocyte population CD3+(MD=8.68,95%CI[4.97,12.39],Z = 4.59,P＜0.000 01)and CD4+(MD=10.77,95%CI[5.46,16.08],Z = 3.97,P＜0.000 1)levels,and reduced the incidence of postoperative complications of thyroid cancer(RR=0.34,95%CI[0.18,0.65],Z = 3.26,P = 0.001).The differences were all statistically significant(P＜0.05).Conclusion prescriptions for softening hardness to dissipate mass combined with Levothyroxine Sodium can enhance the efficacy of postoperative patients with thyroid cancer.The combined therapy is superior to Levothyroxine Sodium alone in improving thyroid function indicators,KPS score,time for the relief of clinical symptoms,diameter of the largest thyroid nodule,immune function indicators,and the incidence of postoperative complications.However,due to the small amount of included trials and the fact that the prescriptions for softening hardness to dissipate mass vary in the composition,the conclusions of the analysis need to be confirmed by more high-quality,multi-center,large-sample clinically randomized controlled trials.

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Cardiac contractility modulation(CCM),as a new implantable electronic therapy device for treating chronic heart failure with reduced ejection fraction(HFrEF),has rapidly become a hot topic in the cardiovascular field due to its ability to enhance ventricular myocardial contractility,improve patients'symptoms and signs,cardiac function indexes and even long-term prognosis.This article reviews the mechanism and clinical studies of CCM in treating HFrEF,and based on its mechanism and signal transduction algorithm,further analyzes and prospects its efficacy in patients with heart failure with preserved ejection fraction,cardiac resynchronization therapy non-response,and HFrEF with concomitant atrial fibrillation,aiming to promote CCM to meet the needs of more diverse clinical situations in heart failure patients.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To establish a new classification system for distal clavicle fracture and evaluate its clinical effectiveness.Methods:A retrospective case series study was conducted to analyze the clinical data of 101 patients with distal clavicle fracture admitted to First Affiliated Hospital of Nanjing Medical University from January 2015 to March 2022, including 57 males and 44 females, aged 19-86 years [(53.8±14.0)years]. Before treatment, patients were routinely subjected to bilateral anteroposterior radiography of the shoulder joints to measure the length of the fractured fragments, coracoclavicular distance, and acromioclavicular distance. According to the correlation between the location of the fracture line and the insertion of the coracoclavicular ligament, distal clavicle fracture was divided into three types: type I, with the fracture line lateral to the coracoclavicular ligament region; type II, with the fracture line in the coracoclavicular ligament region; type III, with the fracture line medial to the coracoclavicular ligament region. According to the injury severity of the coracoclavicular ligament and acromioclavicular ligament, type I was further subdivided into type IA, IB, IC and ID, and type II fracture was further subdivided into type IIA, IIB, IIC, IID and IIE. All the 101 patients were classified and randomly reclassified at an interval of 3 months by 10 senior and 10 junior shoulder surgeons according to the new classification method. Kappa coefficients were used to evaluate the inter- and intra-observer consistency of the new classification. Fifty-two patients with stable fracture (types IA, IB, IIC, and IID) were treated non-surgically, while 49 patients with unstable fracture (types IC, ID, IIA, IIB, IIE, and III) were treated surgically, including 26 patients with anatomic coracoclavicular ligament reconstruction, 9 with locking plate fixation, 8 with clavicle hook plate fixation, 4 with anatomic coracoclavicular ligament reconstruction combined with locking plate fixation, and 2 with anatomic coracoclavicular ligament reconstruction combined with tension screw fixation. The patients were assessed using the visual analogue scale (VAS) and Constant-Murley shoulder score before treatment and at 3, 6, 12, and 18 months after treatment. The coracoclavicular distance and acromioclavicular distance on the anteroposterior radiographs of the healthy and affected shoulder joints were measured at 3, 6, 12, and 18 months after treatment, and fracture healing time and complications were observed.Results:The length of the fractured fragments was 12.9 (9.7, 17.6)mm in patients with type I fracture, 24.7 (21.8, 27.8)mm in patients with type II fracture, and 43.6 (41.2, 46.9)mm in patients with type III fracture ( P<0.01). There were no significant differences in the coracoclavicular distance and acromioclavicular distance of the affected and healthy shoulders among the patients with types IA, IB, IIC, IID, and III fracture ( P>0.05); For the patients with types IC, IIA, IIB and IIE fracture, the coracoclavicular distance of the affected shoulder was significantly increased compared with that of the healthy shoulder ( P<0.01), while there was no significant difference in the acromioclavicular distance of the affected and healthy shoulders ( P>0.05). Both of the inter- and intra-observer consistency of the new classification was good. The inter- and intra-observer Kappa values were 0.69 and 0.71 respectively among the senior shoulder surgeons, and 0.61 and 0.64 respectively among the junior shoulder surgeons. All the patients were followed up for 18-104 months [28(23, 32)months]. At 3, 6, 12 and 18 months after treatment, the VAS scores of non-surgical patients were 3(2, 3)points, 2(1, 2)points, 1(0, 1)points and 0(0, 1)points respectively, significantly decreased compared with 6(5, 6)points before treatment ( P<0.01); the VAS scores of surgical patients were 3(2, 3)points, 2(1, 2)points, 1(1, 1)points and 0(0, 1)points respectively, significantly decreased compared with 6(5, 7)points before treatment ( P<0.01); the Constant-Murley shoulder scores of non-surgical patients were (76.6±5.3)points, (84.3±5.0)points, (88.4±4.0)points and (91.9±3.8)points respectively, significantly higher than (42.7±5.2)points before treatment ( P<0.01); the Constant-Murley shoulder scores of surgical patients were (77.4±4.6)points, (84.4±4.7)points, (87.6±3.7)points and (91.7±4.0)points respectively, significantly higher than (42.8±5.3)points before treatment ( P<0.01). At 3, 6, 12 and 18 months after treatment, the coracoclavicular distance of the affected shoulder in non-surgical patients was not significantly different from that before treatment ( P>0.05), while the acromioclavicular distance of the affected shoulder in surgical patients was significantly reduced compared with that before treatment ( P<0.01). There were no significant differences in the coracoclavicular distance of the healthy shoulder or bilateral acromioclavicular distance in non-surgical and surgical patients at 3, 6, 12, and 18 months after treatment compared with those before treatment ( P>0.05). Fractures were healed within 12 months after treatment in all the patients, without dislocation or subluxation of the acromioclavicular joint, internal fixation failure or internal fixator breakage. Eight patients treated with clavicular hook plate fixation had shoulder pain associated with limited mobility after operation, and all underwent a second operation to remove the clavicular hook plate at 12 months after operation. Conclusions:The new classification system for distal clavicle fracture is established, which comprehensively considers the position of the fracture line, injury of the coracoclavicular and acromioclavicular ligaments, and fracture stability. The new classification system exhibits good inter- and intra- observer consistency, and the effectiveness of its preliminary clinical application is satisfactory.

Objective:To construct an estimating equation to accurately reflect the aging phenomenon of the glomerular filtration rate(GFR).Methods:Healthy subjects receiving physical examinations at the First Affiliated Hospital of Nanjing Medical University between January 2017 and April 2018 were included in the study, and the aging phenomenon of renal function indicators such as serum creatinine(Scr)was used as the reference standard to evaluate the accuracy of four Scr-based GFR equations during GFR aging, including the full age spectrum(FAS)equation, the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)equation, the Osaka equation and the Xiangya equation.Results:Of 37 636 individuals receiving physical examinations, 6 534 met the criteria specified in this study.Scr, serum urea nitrogen, serum uric acid, and serum albumin showed a significant aging phenomenon( H=191.640, 196.693, 83.271, 414.585, P<0.001 for all).The GFR estimated by the four equations all decreased with aging, but the starting point and rate of decline were significantly different.The GFR aging phenomenon estimated by the FAS equation was closer to the trend of renal function indicators. Conclusions:The FAS equation may be more applicable to healthy people to understand the aging phenomenon of GFR.

BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

Humans ; Infant ; Female ; Dandy-Walker Syndrome/diagnosis* ; Tomography, X-Ray Computed ; Craniocerebral Trauma/complications*