Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Acute cerebral infarction(ACI)has the characteristics of onset nasty and high mortality,and thus the rapid determination of the occurrence and development of ACI plays a key role in the diagnosis,treatment and prognosis of ACI patients.It has shown that the serum level of human haptoglobin(Hp)is related to ACI.In this study,surface enhanced Raman scattering(SERS)combined with immune recognition was applied to establish a quantitative analysis method for serum Hp.Firstly,the SERS substrate of silver nanoparticles was prepared on silicon wafer,and 4-mercaptobenzoic Acid(MBA)was used as a Raman probe by forming Ag—S bond and connecting it on the surface of nanoparticles.The carboxyl group of MBA was linked to amino group of self-made high-affinity antibody through forming CO—NH structure thus forming a SERS self-assembled chip of Hp(Ag/MBA/anti-Hp).Hp in serum could be specifically captured by antibodies on SERS substrate,which caused the shift of SERS characteristic peak of MBA.The results showed that there was a good linear relationship between the logarithm of Hp concentration and the SERS characteristic peak shift of MBA.The detection range was 1-1000 ng/mL(R2=0.988).The Hp concentrations in serum of 90 ACI patients were determined by this method,and the results were consistent with those of ELISA method,which proved the practicability and accuracy of this method.This method was highly specific,simple and convenient,which could realize the specific recognition and quantitative analysis of serum Hp,so as to be an effective means for clinical detection of serum Hp,thus providing a reference for the treatment and prognosis of ACI.

Purpose::To assess the value of the driving pressure variation rate (ΔP%) in predicting the outcome of weaning from invasive mechanical ventilation in patients with acute respiratory distress syndrome.Methods::In this case-control study, a total of 35 patients with moderate-severe acute respiratory distress syndrome were admitted to the intensive care unit between January 2022 and December 2022 and received invasive mechanical ventilation for at least 48 h were enrolled. Patients were divided into successful weaning group and failed weaning group depending on whether they could be removed from ventilator support within 14 days. Outcome measures including driving pressure, PaO 2:FiO 2, and positive end-expiratory pressure, etc. were assessed every 24 h from day 0 to day 14 until successful weaning was achieved. The measurement data of non-normal distribution were presented as median (Q 1, Q 3), and the differences between groups were compared by Wilcoxon rank sum test. And categorical data use the Chi-square test or Fisher's exact test to compare. The predictive value of ΔP% in predicting the outcome of weaning from the ventilator was analyzed using receiver operating characteristic curves. Results::Of the total 35 patients included in the study, 17 were successful vs. 18 failed in weaning from a ventilator after 14 days of mechanical ventilation. The cut-off values of the median ΔP% measured by Operator 1 vs. Operator 2 in the first 4 days were ≥ 4.17% and 4.55%, respectively ( p < 0.001), with the area under curve of 0.804 (sensitivity of 88.2%, specificity of 64.7%) and 0.770 (sensitivity of 88.2%, specificity of 64.7%), respectively. There was a significant difference in mechanical ventilation duration between the successful weaning group and the failure weaning group (8 (6, 13) vs. 12 (7.5, 17.3), p = 0.043). The incidence of ventilator-associated pneumonia in the successful weaning group was significantly lower than in the failed weaning group (0.2‰ vs. 2.3‰, p = 0.001). There was a significant difference noted between these 2 groups in the 28-day mortality (11.8% vs. 66.7%, p = 0.003). Conclusion::The median ΔP% in the first 4 days of mechanical ventilation showed good predictive performance in predicting the outcome of weaning from mechanical ventilation within 14 days. Further study is needed to confirm this finding.

Remazolam is a γ-aminobutyric acid(GABA)receptor agonist.It is a short-acting benzodiazepine drug that has just been launched in China in recent years.Its mechanism of action is to enhance inhibitory neurotransmitters of GABA in the central nervous system.It has been widely used in clinical practice for sedation,hypnosis,anti anxiety,and the treatment of insomnia.Meanwhile,remazolam is mainly used for induction and maintenance of general anesthesia during the perioperative period,with a fast onset time and a brief duration of action.Recent studies have shown that remazolam can protect important organs and alleviate organ damage by reducing inflammatory responses and oxidative stress,regulating cell apoptosis,and other pathways.This article summarizes the protective effects and mechanisms of remazolam on the brain,heart,liver,and lung,providing a theoretical basis for the clinical application of remazolam.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

Objective:To investigate the efficacy of posterior reduction and fixation combined with pedicle subtraction osteotomy (PSO) in the treatment of ankylosing spondylitis (AS) kyphotic deformity complicated by upper cervical spine injury.Methods:A retrospective case series study was conducted to analyze the clinical data of 8 patients with AS kyphotic deformity complicated by upper cervical spine injury, who were admitted to First Affiliated Hospital of Xinjiang Medical University from October 2010 to December 2022. All were males, aged 32-58 years [(46.9±8.7)years]. Acute injury was found in 1 patient and chronic injuries in 7 patients, including 3 with cervicothoracic kyphotic deformity and 5 with thoracolumbar kyphotic deformity. Five patients were complicated by odontoid fractures, 1 by C 2-C 3 fracture and 2 by atlantoaxial dislocation. According to American Spinal Injury Association (ASIA) scale, 2 patients were with grade C, 3 with grade D, and 3 with grade E. The patients were treated with posterior upper cervical reduction and fixation combined with cervicothoracic PSO or thoracolumbar PSO respectively according to the location of the deformity. The operation time and intraoperative blood loss were recorded. Neck disability index (NDI), visual analogue scale (VAS), C 0-C 2 angle, C 1-C 2 angle, cervical lordosis angle (CL), head tilt angle (HT), chin-brow vertical angle (CBVA), cervical sagittal vertical axis (CSVA), and sagittal vertical axis (SVA) were compared before surgery, at 1 week and 3, 6, 12 months after surgery, and at the last follow-up. The healing of fractures and fusion of osteotomy site were recorded at 12 months after surgery. Recovery of neurological function was observed at the last follow-up. Incidence of complications was observed. Results:Patients were all followed up for 12-24 months [(17.0±5.4)months]. The operation time was 5.5-7.2 hours [(6.2±0.6)hours] and the intraoperative blood loss was 480-800 ml [(629.4±124.0)ml]. The NDI scores at 1 week and 3, 6, 12 months after surgery, and at the last follow-up were (14.6±2.6)points, (13.6±2.8)points, (12.8±2.4)points, (12.8±2.7)points, and (12.8±2.6)points respectively, significantly lower than (29.6±8.5)points preoperatively ( P<0.01). There were no significant differences in NDI scores at various time points after surgery ( P>0.05). The VAS scores were 2.0(1.0, 3.0)points, 1.5(1.0, 2.0)points, 0.5(0.0, 1.8)points, 0.5(0.0, 1.7)points, and 0.5(0.0, 1.8)points respectively, significantly lower than 3.5(3.0, 4.8)points preoperatively ( P<0.01). The VAS score at 3 months postoperatively was lower than that at 1 week postoperatively ( P<0.05), and the VAS score at 6 months postoperatively was lower than that at 3 months postoperatively ( P<0.05). There were no statistically significant differences in VAS scores at 6, 12 months postoperatively, and at the last follow-up ( P>0.05). There were no statistically significant differences between C 0-C 2 angle and C 1-C 2 angle preoperatively and at different time points postoperatively ( P>0.05). At 1 week and 3, 6, 12 months postoperatively and at the last follow-up, the CL values were -8.5(-5.3, -11.9)°, -8.6(-5.5, -11.9)°, -8.4(5.2, -12.1)°, -8.8(-5.6, -12.4)°, and -8.7(-5.3, -12.5)° respectively, significantly higher than 1.2(9.5, -4.8)° preoperatively ( P<0.01); the HT values were 6.1(4.5, 9.6)°, 6.1(4.3, 9.4)°, 6.0(4.2, 8.9)°, 6.0(4.2, 9.2)°, and 6.1(4.3, 9.2)° respectively, significantly lower than 17.0(10.3, 22.0)° preoperatively ( P<0.01); the CBVA values were (23.2±5.0)°, (23.1±4.8)°, (23.0±4.7)°, (23.1±4.7)°, and (23.1±4.9)° respectively, significantly lower than (44.1±9.8)° preoperatively ( P<0.01); the CSVA values were 5.2(4.2, 7.5)cm, 5.4(4.1, 7.1)cm, 4.7(4.0, 7.4)cm, 5.4(4.1, 7.0)cm, and 5.1(4.3, 6.5)cm respectively, significantly shorter than 9.0(7.8, 9.3)cm preoperatively ( P<0.01); the SVA values were 7.7(6.2, 13.7)cm, 7.5(6.0, 13.4)cm, 7.6(6.2, 13.2)cm, 7.4(6.3, 13.1)cm, and 7.5(6.2, 13.2)cm respectively, significantly shorter than 16.8(8.2, 27.2)cm preoperatively ( P<0.05). There were no statistically significant differences among CL, HT, CBVA, CSVA, and SVA values at different time points after surgery ( P>0.05). All the fractures healed at 12 months after surgery and Bridwell grade I healing was achieved at all the osteotomy sites. At the last follow-up, all the patients were classified as ASIA grade E, significantly improved compared with preoperatively ( P<0.01). One patient had transient C 8 nerve paralysis after surgery and recovered after 4 weeks′ treatment. The remaining patients did not develop any infection or internal fixation-related complications, such as broken rods, broken screws, or loose screws. Conclusion:For AS kyphosis deformity complicated with upper cervical injury, posterior reduction and fixation combined with cervicothoracic or thoracolumbar PSO can effectively promote functional recovery, relieve pain, maintain overall trunk balance, improve neurological symptoms, and reduce the incidence of complications.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Postoperative cognitive dysfunction(POCD)is one of the common complications in the perioperative period,and it has a high incidence in elderly patients,and the large production of neuroinflammatory factors under surgical stimulation is the main cause of postoperative POCD.As an ultra-short-acting benzodiazepine of γ-aminobutyric acid receptor agonist,remimazolam can play a sedative-hypnotic and anxiolytic role in clinical practice,and can reduce inflammatory factors in the central nervous system and improve postoperative cognitive dysfunction by inhibiting neuroinflammatory response and oxidative stress.This article reviews the protective effect and mechanism of remimazolam on postoperative cognitive function,so as to provide a basis for the clinical use of remimazolam.

Humans ; Mycobacterium tuberculosis/genetics* ; Microspheres ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Fluoroquinolones ; Drug Resistance, Bacterial/genetics* ; Tuberculosis, Multidrug-Resistant/microbiology*

Objective: To investigate the association of mixed exposure to greenness and nitrogen dioxide(NO₂) and hypertension among the older adults aged 65 years and over in China. Methods: The study subjects were from the Chinese Longitudinal Healthy Longevity Survey from 2017 to 2018. A total of 15 423 older adults aged 65 years and over meeting the criteria were finally included in the study. A questionnaire survey was used to collect information on demographic characteristics, lifestyle habits and self-reported prevalence of hypertension. Blood pressure values were obtained through physical examination. The level of normalized difference vegetation index(NDVI) was measured by the Medium-resolution Imaging Spectral Radiator(MODIS) of the National Aeronautics and Space Administration(NASA). The concentration of NO₂ was from China's surface air pollutant data set. Meteorological data was from NASA MERRA-2. The exposure to NDVI and NO₂ for each study subject was calculated based on the area within a 1 km radius around their residence. The association between mixed exposure of NDVI and NO₂ as well as their interaction and hypertension in older adults was analyzed by using the multivariate logistic regression model. The restrictive cubic spline(RCS) function was used to explore the exposure-response relationship between greenness and NO₂ and the risk of hypertension in study subjects. Results: The mean age of 15 423 older adults were (85.6±11.6). Women accounted for 56.3%(8 685/15 423) and 55.6%(8 578/15 423) lived in urban areas. The mean time of residence was (60.9±28.5) years. 59.8% of participants were with hypertension. The mean NDVI level was 0.41±0.13, and the mean NO₂ concentration was (32.18±10.36) μg/cm³. The results of multivariate logistic regression analysis showed that NDVI was inversely and linearly associated with the hypertension in older adults, with the OR(95%CI) value of 0.959(0.928-0.992). Compared with the T₁ group of NDVI, the risk of hypertension was lower in the T₃ group, with the OR(95%CI) value of 0.852(0.769-0.944), and the trend test was statistically significant(P<0.05). Compared with the T₁ group of NO₂, the risk of hypertension was higher in the T₂ and T₃ groups, with OR(95%CI) values of 1.160(1.055-1.275) and 1.244(1.111-1.393), and the trend test was statistically significant (P<0.05). The result of the RCS showed that NDVI was inversely and linearly associated with hypertension in older adults. NO₂ was nonlinearly associated with hypertension in older adults. The interaction analysis showed that NDVI and NO₂ had a negative multiplicative interaction on the risk of hypertension, with OR(95%CI) value of 0.995(0.992-0.997). Conclusion: Exposure to greenness and NO₂ are associated with hypertension in older adults.
Aged ; Humans ; Female ; Nitrogen Dioxide ; Air Pollution ; Prevalence ; Hypertension/epidemiology* ; China/epidemiology* ; Particulate Matter/analysis*