Background: Intraoperative hypercapnia reduces the time to emergence from volatile anesthetics, but few clinical studies have explored the effect of hypercapnia on the emergence time from intravenous (IV) anesthesia. We investigated the effect of inducing mild hypercapnia during the recovery period on the emergence time after total IV anesthesia (TIVA). Methods: Adult patients undergoing transurethral lithotripsy under TIVA were randomly allocated to normocapnia group (end-tidal carbon dioxide [ETCO2] 35–40 mmHg) or mild hypercapnia group (ETCO2 50-55 mmHg) during the recovery period. The primary outcome was the extubation time. The spontaneous breathing-onset time, voluntary eye-opening time, and hemodynamic data were collected. Changes in the cerebral blood flow velocity in the middle cerebral artery were assessed using transcranial Doppler ultrasound. Results: In total, 164 patients completed the study. The extubation time was significantly shorter in the mild hypercapnia (13.9 ± 5.9 min, P = 0.024) than in the normocapnia group (16.3 ± 7.6 min). A similar reduction was observed in spontaneous breathing-onset time (P = 0.021) and voluntary eye-opening time (P = 0.008). Multiple linear regression analysis revealed that the adjusted ETCO2 level was a negative predictor of extubation time. Middle cerebral artery blood flow velocity was significantly increased after ETCO2 adjustment for mild hypercapnia, which rapidly returned to baseline, without any adverse reactions, within 20 min after extubation. Conclusions Mild hypercapnia during the recovery period significantly reduces the extubation time after TIVA. Increased ETCO2 levels can potentially enhance rapid recovery from IV anesthesia.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

ObjectiveTo investigate a suspected outbreak of healthcare-associated infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) in a geriatric emergency ward, and to provide references for the prevention and control of multidrug-resistant bacteria in a hospital in Shanghai. MethodsOn-site epidemiological investigation, combined with environmental hygiene monitoring and pulsed field gel electrophoresis (PFGE) molecular typing method, were adopted to investigate a suspected outbreak of CRKP infection in the geriatric emergency ward of a hospital from October to November 2022, aiming at finding out factors caused the outbreak before taking corresponding control measures. ResultsA total of 3 cases of healthcare-associated CRKP infection were identified, of which 2 cases were homologous to a previous case of community-associated CRKP infection. What’s more, the 2 cases lived in the same ward with the latter and with adjacent beds, but the third case was non-homologous to the community-associated infection case. A total of 46 samples were collected from the environmental surfaces and the hands of healthcare workers, of which 7 samples tested positive for CRKP and were identical to the strains from the 2 healthcare-associated infection cases and the 1 community-associated infection case, originating from the bedrails, bedside tables, surface of non-invasive ventilator, bed curtains and panels of monitoring equipment, with a detection rate of 15.22%. But none of the 11 samples from the hands of healthcare workers tested positive for CRKP. The outbreak was effectively controlled after taking specific prevention and control measures such as strengthening personnel management, intensifying environmental cleaning and disinfection and strictly enforcing hand hygiene among healthcare workers. Subsequently, no similar new cases were reported during the 14-day follow-up period. ConclusionIncomplete environmental cleaning and disinfection, as well as inadequate enforcement of hand hygiene among heatheare workers may have contributed to the suspected outbreak of CRKP in the geriatric emergency ward. Early warning and timely investigation of suspected outbreaks of multidrug-resistant bacteria are crucial for preventing and controlling such outbreaks in hospitals.

Stroke is the main cause of death and disability among adults in China and is characterized by high incidence， disability， mortality， and recurrence rates. The combination of traditional Chinese and Western medicine has great potential in treating stroke and its sequelae. The classic traditional Chinese medicine prescription Da Chengqitang （DCQT） has a long history and proven efficacy in treating stroke. Clinically， DCQT is often used to treat stroke and its sequelae. However， the number and quality of clinical trials of DCQT in treating stroke need to be improved. Because of the insufficient basic research， the active ingredients and multi-target mechanism of action of DCQT remain unclear. Our research group has previously confirmed that DCQT can effectively reverse neurological damage， reduce iron deposition， and downregulate the levels of pro-inflammatory cytokines in the rat model of hemorrhagic stroke. The treatment mechanism is related to the nuclear factor erythroid 2-related factor 2 （Nrf2）-mediated signaling pathway and p38 mitogen-activated protein kinase （MAPK） signaling-mediated microglia activation. To clarify the pharmacodynamic basis and anti-stroke mechanism of DCQT， this article reviews the research progress in the treatment of stroke with DCQT in terms of clinical trials， pharmacodynamic material basis， safety evaluation， and mechanisms of absorbed components. This article summarizes 45 major phytochemical components of DCQT， 11 of which are currently confirmed absorbed components. Among them， emodin， rhein， chrysophanol， aloe-emodin， synephrine， hesperidin， naringin， magnolol， and honokiol can be used as quality markers （Q-markers） of DCQT. The mechanism of DCQT in treating stroke is complex， involving regulation of inflammatory responses， neuronal damage， oxidative stress， blood-brain barrier， brain-derived neurotrophic factor， and anti-platelet aggregation. This article helps to deeply understand the pharmacodynamic basis and mechanism of DCQT in treating stroke and provides a theoretical basis for the clinical application of DCQT in treating stroke and the development of stroke drugs.

Objective: To explore the bidirectional causal relationship between 731 immune cell phenotypes and recurrent aphthous ulcers (RAU) using Mendelian randomization (MR). Methods: A two-sample bidirectional MR study was conducted using publicly available genome-wide association study (GWAS) summary statistics for 731 immune cell phenotypes and the RAU GWAS summary data from the FinnGen consortium. The inverse-variance weighted (IVW) method was used as the primary analysis tool, with supplementary analyses including the weighted median (WM) method, MR-Egger regression, weighted mode, and simple mode. Sensitivity analyses were conducted using Cochran’s Q test, the mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method for detecting pleiotropy and outliers, and leave-one-out cross-validation. Furthermore, differential analysis was performed using a clinical cohort dataset from the Gene Expression Omnibus (GEO) to further validate the MR results. Results: In the forward MR analysis, 731 immune cell phenotypes were considered as exposures and RAU as the outcome. Among them, 52 immune cell phenotypes showed a significant causal effect on RAU (P<0.05). After false discovery rate (FDR) correction, two immune phenotypes remained significantly associated with RAU risk: with increased monocyte-derived myeloid suppressor cells (M-MDSC) (OR = 1.06; 95% CI: 1.03-1.09) and CD33 on granulocytic myeloid-derived suppressor cells (G-MDSC) (OR = 1.06; 95% CI: 1.03-1.09), the risk of RAU also increased. In reverse MR, RAU was found to have a significant causal effect on two immune cell phenotypes (P<0.05), but no significant effects were found after FDR correction. Sensitivity analysis showed no significant heterogeneity between SNPs (P>0.05). Differential analysis of the GEO dataset revealed that the characteristic genes of myeloid-derived suppressor cells (MDSC) (CTBS, IPMK, and UBA3) were significantly upregulated in RAU (P<0.05). Conclusion The MR results of 731 immune cell phenotypes suggest that M-MDSC and CD33 molecules on G-MDSC may be risk factors for RAU development. The clinical GEO dataset further validated that MDSC may play a role in RAU, while RAU did not show a significant causal association with the 731 immune cell phenotypes.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveBased on the concept of quality by design（QbD）， the processing process of calcined Pyritum was optimized， and its X-ray diffraction（XRD） fingerprint was established. MethodsThe safety， effectiveness and quality controllability of calcined Pyritum were taken as the quality profile（QTPP）， the color， hardness， metallic luster， phase composition， the contents of heavy metals and hazardous elements were taken as the critical quality attributes（CQAs）， and the calcination temperature， calcination time， paving thickness and particle size were determined as the critical process parameters（CPPs）. Differential thermal analysis， X-ray diffraction（XRD） and inductively coupled plasma mass spectrometry（ICP-MS） were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then， based on the criteria importance through intercriteria correlation（CRITIC）-entropy weight method， the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process， and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures， and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS₂ to Fe₇S₈ during the process of temperature increase， the color gradually deepened from dark yellow， and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows：calcination temperature at 750 ℃， calcination time of 2.5 h， paving thickness of 3 cm， particle size of 0.8-1.2 cm， vinegar quenching 1 time［Pyritum-vinegar（10∶3）］. After calcination， the internal structure of Pyritum was honeycomb-shaped， which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96， and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing， the dissolution of the effective components in Pyritum increases， and the contents of heavy metals and harmful substances decrease， reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible， and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.

ObjectiveTo explore the construction and evaluation methods of a rat model of acute myocardial infarction（AMI） with Qi and Yin deficiency syndrome established by sleep deprivation combined with coronary artery ligation. MethodsThirty-six SD rats were randomly divided into a normal group（n=6）， a myocardial infarction group（model A group， n=10）， an acute sleep deprivation+myocardial infarction group（model B group， n=10）， and a chronic sleep deprivation+myocardial infarction group（model C group， n=10） according to body weight. Rats in the normal group were not treated， rats in the model A group underwent only ligation of the left anterior descending coronary artery， rats in the model B group were sleep deprived for 96 h and then underwent ligation of the left anterior descending coronary artery， and rats in the model C group were sleep deprived for an additional 48 h each week with a 24 h rest period as one cycle for three weeks on the basis of the model B group. After coronary artery ligation in the model C group， the first week was defined as the starting point of the first sleep deprivation cycle， and indexes were tested weekly for rats in each group for 3 weeks. Electrocardiogram was used to determine the ligation of the left anterior descending coronary artery in rats， and small animal echocardiography was used to evaluate the cardiac function. The levels of serum creatine kinase（CK）， creatine kinase isoenzyme（CK-MB）， lactate dehydrogenase（LDH）， cardiac troponin T（cTnT）， interleukin-18（IL-18）， and tumor necrosis factor-α（TNF-α） were detected by biochemical assays， and hematoxylin-eosin（HE） staining was used to evaluate the pathological changes of myocardial tissue in rats. The syndrome indicators of Qi and Yin deficiency were evaluated by general state and body weight， grip strength， facial temperature， paw temperature， rectal temperature， salivary flow rate， open field test， tongue color［red（R）， green（G）， and blue（B）］ values， pulse amplitude changes， and enzyme-linked immunosorbent assay（ELISA） for the detection of expression levels of cyclic adenosine monophosphate（cAMP）， cyclic guanosine monophosphate（cGMP）， rat serum corticotropin-releasing factor（CRF）， adrenocorticotropic hormone（ACTH）， triiodothyronine（T3）， tetraiodothyronine（T4）， and corticosterone（CORT） in serum. ResultsIn terms of disease indicators， compared with the normal group， the ST segment of the electrocardiogram in each model group was significantly elevated， the echocardiographic parameters were decreased， the contents of myocardial enzymes and inflammatory factors were increased（P<0.01）， and the myocardial tissue in the infarcted area was significantly damaged. In terms of syndrome indicators， compared with the normal group， the body weight of rats in the model B and C groups decreased at each time point， the grip strength of each model group decreased， the total distance traveled and the number of entries into the center in the open field test decreased， the immobility time increased， the facial and rectal temperatures of rats in the model B and C groups increased， the salivary flow rate of each model group decreased， the tongue color was bright red or light， the tongue body was dry or smooth like a mirror， lacking of moisture sensation， the R， G and B values of the tongue surface increased， the pulse amplitude changes decreased， and the contents of T3 and T4 increased， while the expressions of cAMP， CRF， ACTH and CORT in the model B and C groups increased（P<0.05， P<0.01）. ConclusionContinuous sleep deprivation for 96 h in a multi-platform method combined with coronary artery ligation can construct a rat model of AMI with Qi and Yin deficiency syndrome， and the syndrome manifestations can be maintained for 3 weeks.

ObjectiveTo explore the feasibility， evaluation methods and metabolic differences of high-fat diet（HFD） combined with myocardial ischemia-reperfusion injury（MIRI） to establish a rat model of myocardial ischemia-reperfusion with phlegm and blood stasis blocking collaterals syndrome（PBSBCS）. MethodsThirty-two SD rats were randomly divided into the sham operation， HFD， MIRI， and MIRI+HFD groups. Rats in the sham operation and MIRI groups were fed a standard diet（regular chow）， while the HFD and MIRI+HFD groups received a HFD for 10 weeks. Rats in the MIRI and MIRI+HFD groups underwent myocardial ischemia-reperfusion surgery， while the sham operation group underwent only thread placement without ligation. Cardiac function was assessed via small-animal echocardiography， including left ventricular ejection fraction（EF）， left ventricular fractional shortening（FS）， cardiac output（CO）， and stroke volume（SV）. Serum levels of creatine kinase（CK）， CK-MB， triglyceride（TG）， total cholesterol（TC）， high-density lipoprotein cholesterol（HDL-C）， low-density lipoprotein cholesterol（LDL-C）， lactate dehydrogenase（LDH）， endothelin-1（ET-1）， endothelial nitric oxide synthase（eNOS）， tumor necrosis factor-α（TNF-α）， interleukin-18（IL-18）， oxidized LDL（ox-LDL）， and cardiac troponin T（cTnT） were measured by biochemical assays and enzyme-linked immunosorbent assay（ELISA）. Myocardial histopathology was evaluated via hematoxylin-eosin（HE） staining， while myocardial infarction and no-reflow area were assessed using 2，3，5-triphenyltetrazolium chloride（TTC）， Evans blue， and thioflavin staining. Changes in syndrome characteristics［body weight， tongue surface red-green-blue ［RGB］ values， and pulse amplitude］ of PBSBCS were recorded. Serum differential metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）. ResultsCompared with the sham operation group， the HFD and MIRI+HFD groups showed significant increases in body weight（P<0.01）， RGB values and pulse amplitude decreased in the HFD， MIRI and MIRI+HFD groups， TC， TG， LDL-C and ox-LDL levels increased in the HFD and MIRI+HFD groups， while HDL-C decreased. Blood perfusion peak time and myocardial no-reflow area increased， serum eNOS level decreased， and CK-MB， LDH， and cTnT activities increased in the HFD， MIRI and MIRI+HFD groups（P<0.05， P<0.01）. Whole blood viscosity was increased in the HFD group at medium shear rate， and in the MIRI and MIRI+HFD groups at low， medium and high shear rates（P<0.05， P<0.01）. Platelet aggregation rate increased in the MIRI and MIRI+HFD groups， accompanied by elevated ET-1， TNF-α， and IL-18 levels， reduced cardiac function indices， expanded myocardial no-reflow and infarction areas， and increased serum CK， CK-MB， LDH， and cTnT activities（P<0.05， P<0.01）. Compared with the MIRI group， the HFD and MIRI+HFD groups showed significant increase in body weight， TC， TG， LDL-C and ox-LDL levels， and significant decrease in HDL-C content（P<0.01）. The MIRI+HFD group showed decrease in RGB values and pulse amplitude， and an increase in whole blood viscosity， platelet aggregation， blood perfusion peak time， myocardial no-reflow and infarction areas， elevated ET-1， TNF-α and IL-18 levels， decreased eNOS content， EF and SV， increased serum CK， CK-MB and cTnT activities， and worsened myocardial pathology（P<0.05）. Compared with the HFD group， the MIRI+HFD group showed similar aggravated trends（P<0.05， P<0.01）. Metabolomics results showed that 34 potential biomarkers involving 13 common metabolic pathways were identified in the MIRI+HFD group compared with the sham operation group. ConclusionThe MIRI group resembles blood stasis syndrome in hemodynamics and myocardial injury， and the HFD group mirrors phlegm-turbidity syndrome in lipid profiles and tongue characteristics. While the MIRI+HFD group aligns with PBSBCS in comprehensive indices， effectively simulating clinical features of coronary heart disease（CHD）， which can be used for the evaluation of the pathological mechanism and pharmacodynamics of CHD with PBSBCS.