The abuse of novel phenylcyclohexylpyridine drugs poses a significant threat to societal safety. The novel psychoactive substance 2-methyl-deschloroketamine (2-MDCK), belonging to the phenylcyclohexylpyridine class, has recently surfaced as a new compound. However, there is a lack of understanding regarding its metabolic pathways and the identification of suitable biomarkers. In this study, a human liver microsomal model was established, and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technology was applied to investigate the in vitro metabolism and products of 2-MDCK. The results indicate that 2-MDCK undergoes various metabolic reactions, including dehydrogenation, deamination, hydroxylation, and demethylation, leading to the formation of eight metabolites. By conducting actual testing on hair samples from 2-MDCK abusers, the existence of six metabolites was confirmed. Comparing the metabolic products in the liver microsomal in vitro model, M3.1 and M4.1 were identified as biomarkers for 2-MDCK consumption. Five samples of abusers of 2-methyl-dechloroketamine were provided by the Anti-Drug Brigade of the Hangzhou Public Security Bureau. Negative hair samples were provided by laboratory volunteers, and all samples were obtained with the informed consent of the volunteers. These findings provide a scientific basis for the detection and identification of 2-MDCK and its metabolites, as well as crucial support for the study of the metabolic mechanisms of similar novel psychoactive substances in the phenylcyclohexylpyridine class. This research holds significant importance in addressing the issue of abuse of new psychoactive substances.

Objective:To investigate the indications and effects of arthroscopic all-inside reconstruction in the treatment of isolated posterior cruciate ligament (PCL) injury.Methods:A retrospective analysis was performed on 47 patients with isolated PCL injury, who underwent arthroscopic all-inside reconstruction in the Third Medical Center of the PLA General Hospital from January 2016 to January 2020. There were 39 males and 8 females, aged 27.14±7.70 years old (range 16-40 years old). The preoperative kneeling-position stress X-ray showed that the degree of tibial posterior displacement was 8-10 mm, which was a complete and isolated Grade II PCL injury. The tibial and femoral tunnels were created through posterior-medial, anteromedial, and anterolateral portals, while the lateral portal to the medial femoral condyle was enlarged to position the tibial tunnel and protect the anterior cruciate ligament. The autologous graft tendon was pulled through the femoral and tibial tunnels secured with an adjustable loop plate. The efficacy was evaluated by evaluating and comparing preoperative and postoperative Lachman test, posterior drawer test, knee range of motion and relaxation, pain visual analogue scale (VAS) and Lysholm score.Results:43 patients were followed up for 35.21±3.88 months (range 12-40 months). The symptoms of knee instability all improved after surgery. At the follow-up of 1 year after surgery, 41 (95%) and 40 (93%) patients showed normal or I-degree laxity in Lachman test and posterior drawer test, respectively. The active range of motion and passive flexion of the knee joint were increased to 90°-110° and 110°-130°, respectively. The Lysholm score was 86.44±4.08 at the first year of follow-up and 90.12±3.33 at the last follow-up with significant difference compared with pre-operations ( P<0.05). The VAS score was 2.07±0.94 at the first year of follow-up and 1.28±0.83 at the last follow-up with significant difference compared with pre-operations ( P<0.05). The Lysholm score and VAS were 90.12±3.33 and 1.28±0.83, which were significantly improved compared to 1-year-follow-up ( P<0.05). Conclusion:Routine kneeling stress X-rays can evaluate the degree of tibial posterior displacement in isolated PCL injuries. With tibial posterior displacement equal to or greater than 10 mm, surgical reconstruction was required. All-inside reconstruction of isolated PCL injury was a safe and minimally invasive surgery to improve symptoms and restore knee functions.

Objective To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation(MPR),and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population.Methods The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected.Volume reconstruction(VR)and MPR were performed on the skull,and 160 cranial suture tomography images were generated for each sample.Then the MPR images of cranial sutures were scored according to the closure grading criteria,and the mean closure grades of sagittal suture,coronal sutures(both left and right)and lambdoid sutures(both left and right)were calculated respectively.Finally taking the above grades as independent variables,the linear regression model and four machine learning models for age estimation(gradient boosting regression,support vector regression,decision tree regression and Bayesian ridge regression)were established for northern Chinese Han adults age estimation.The accu-racy of each model was evaluated.Results Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest.All four machine learning models had higher age estimation accuracy than linear regression model.The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years.Conclusion The combination of skull CT-MPR and machine learning model can be used for age esti-mation in northern Chinese Han adults,but it is still necessary to combine with other adult age estima-tion indicators in forensic practice.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

Objective:To investigate the safety and short-term efficacy of laparoscopic pro-ximal gastrectomy (LPG) for proximal gastric cancer and adenocarcinoma of esophagogastric junction.Methods:The retrospective cohort study was conducted. The clinicopathological data of 385 patients with proximal gastric cancer and adenocarcinoma of esophagogastric junction who underwent LPG in the 15 medical centers, including the First Affiliated Hospital of Xiamen University et al, from January 2014 to March 2022 were collected. There were 304 males and 81 females, aged (63±9)years. Of the 385 patients, 335 cases undergoing LPG were divided into the laparoscopic group and 50 cases undergoing open proximal gastrectomy were divided into the open group. Observation indicators: (1) intraoperative and postoperative situations; (2) follow-up; (3) stratified analysis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Intraoperative and postoperative situations. The operation time, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, cases with postoperative pathological staging as stage 0?Ⅰ and stage Ⅱ?Ⅲ, duration of postoperative hospital stay, cases with postoperative early complications were (212±96)minutes, 270, 65, 177, 107, 10(range, 8?14)days, 40 in patients of the laparoscopic group, with 51 cases missing the data of postoperative pathological staging. The above indicators were (174±90)minutes, 39, 11, 22, 28, 10(range, 8?18)days, 10 in patients of the open group. There were significant differences in the opera-tion time and postoperative pathological staging between the two groups ( t=2.62, χ2=5.93, P<0.05), and there was no significant difference in the reconstruction of digestive tract, duration of post-operative hospital stay, postoperative early complications between the two groups ( χ2=0.19, Z=0.40, χ2=2.50, P>0.05). (2) Follow-up. Of the 385 patients,202 cases were followed up during the post-operative 12 months, including 187 cases in the laparoscopic group and 15 cases in the open group. Cases with reflux esophagitis, cases with esophageal anastomotic stenosis were 48, 11 in patients of the laparoscopic group, versus 5, 2 in patients of the open group, showing no significant difference in the above indicators between the two groups ( P>0.05). The body mass index (BMI), hemoglobin (Hb), albumin (Alb) at postoperative 6 months and 12 months were (21±3)kg/m 2, (130±15)g/L, (40±4)g/L and (21±3)kg/m 2, (132±14)g/L, (41±4)g/L in patients of the laparoscopic group, versus (21±3)kg/m 2, (121±19)g/L, (37±5)g/L and (21±3)kg/m 2, (125±21)g/L, (43±6)g/L in patients of the open group. There were significant differences in postoperative Hb between the two groups ( Fgroup=5.88, Ftime=5.49, Finteraction=19.95, P<0.05) and there were significant differences in time effect of postopera-tive BMI and Alb between the two groups ( Ftime=9.53, 49.88, P<0.05). (3) Stratified analysis. ① Incidence of postoperative of reflux esophagitis and esophageal anastomotic stenosis in patients with different reconstruction of digestive tract. Of the 202 patients, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis were 168 and 34, respectively. The incidence rates of postoperative of reflux esophagitis were 26.79%(45/168)and 23.53%(8/34)in cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, showing no significant difference between them ( χ2=0.16, P>0.05). Cases undergoing esophageal anastomotic stenosis were 13 in patients with reconstruction of diges-tive tract as esophagogastric anastomosis. ② The BMI, Hb, Alb in patients with different reconstruc-tion of digestive tract. The BMI, Hb, Alb were (24±3)kg/m 2, (135±20)g/L, (41±5)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis before the operation, versus (23±3)kg/m 2, (130±19)g/L, (40±4)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis before the operation, showing no significant difference between them ( t=1.44, 1.77, 1.33, P>0.05). The BMI, Hb, Alb at postoperative 6 months and 12 months were (21±3)kg/m 2, (128±16)g/L, (39±4)g/L and (21±3)kg/m 2, (131±16)g/L, (41±4)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis, versus (20±4)kg/m 2, (133±13)g/L, (43±3)g/L and (21±3)kg/m 2, (135±12)g/L, (44±3)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis. There were significant differences in the group effect and time effect of postoperative Alb between patients with different reconstruction of diges-tive tract ( Fgroup=15.82, Ftime=5.43, P<0.05), and there was also a significant difference in the time effect of postoperative BMI between them ( Ftime=4.22 , P<0.05). Conclusion:LPG can be used to the treatment of proximal gastric cancer and adenocarcinoma of esophagogastric junction, with a good safety and short-term efficacy.

Objective:Efficacy and safety of robot-assisted laparoscopic adrenalectomy as a treatment for large adrenal tumors.Three-dimensional(3D) reconstruction can effectively assist in preoperative planning of robotic adrenalectomy and reduce potential complications.Methods:We retrospectively reviewed the relevant information of patients who had a preoperative 3D reconstruction and underwent RA for adrenal masses larger than 10 cm. Thirteen male patients and sixteen female patients were included. The median(range) age was 43(25, 57) years old and the median tumor diameter was 12.1(10.3, 16.2) cm. The patients underwent preoperative CT enhancement scanning, and three-dimensional images were reconstructed based on the examination data. Robot-assisted laparoscopic adrenalectomy was performed under general anesthesia in 29 cases in this cohort.Results:All surgeries were completed successfully without major complications such as massive bleeding, secondary surgery, or even patient death. The median operative time was 131 (80, 245) min, and the median intraoperative bleeding was 330 (50, 2 200 ml) ml. 9 patients received blood transfusions. There were 11 cases of pheochromocytoma (37.9%), 10 cases of adenocarcinoma (34.5%) as well as 2 cases of teratoma (6.9%) and 6 cases of cortical carcinoma (20.7%). The patients were followed up for a median of 30 months after surgery. Except for 3 cases lost to follow-up and 2 patients with cortical cancer who developed recurrence or metastasis after surgery and died at 16 and 23 months after surgery, respectively, the remaining 24 cases have survived to date.Conclusions:RA is a safe and effective treatment for huge adrenal tumors. The 3D reconstruction could help the preoperative planning of RA and reduce potential complications.

Aim To investigate the effects of dagliflozin (DAPA) on atrial tachyarrhythmia (AT) in rats with right heart failure (RHF) due to pulmonary arterial hypertension (PAH) and the underlying mechanisms. Methods Sixty male SD rats were randomly divided into four groups: control group (CTL group), model group (MCT group), MCT + low-dose DAPA intervention group (MCT + LD group) and MCT + high-dose DAPA intervention group (MCT + HD group). After 35 days of continuous intervention, the model and cardiac function evaluation, atrial structural remodelling assessment, inflammatory factor detection, and in vivo cardiac electrophysiology experiments were completed. Results DAPA reduced menn pulmonaryarterial pressure (mPAP) and menn right ventricular pressure (mRVP) in the model rats (P <0.05), attenuated the inflammatory response (P < 0.05), reduced right atrial fibrosis (P <0.05), reduced AT induction rate (P < 0.05) and mean atrial tachyarrhythmia duration (MATD) (P < 0.05), the extent of which was more pronounced in the high-dose DAPA intervention group. Conclusions DAPA can reduce AT susceptibility in PAH-induced RHF rats, and the mechanisms may be related to the inhibition of systemic inflammation and anti-atrial fibrosis by DAPA.

OBJECTIVE: This study aimed to investigate the regulation of histone-like nucleoid structuring protein (H-NS) on biofilm formation and cyclic diguanylate (c-di-GMP) synthesis in Vibrio parahaemolyticus RIMD2210633. METHODS: Regulatory mechanisms were analyzed by the combined utilization of crystal violet staining, quantification of c-di-GMP, quantitative real-time polymerase chain reaction, LacZ fusion, and electrophoretic-mobility shift assay. RESULTS: The deletion of hns enhanced the biofilm formation and intracellular c-di-GMP levels in V. parahaemolyticus RIMD2210633. H-NS can bind the upstream promoter-proximal DNA regions of scrA, scrG, VP0117, VPA0198, VPA1176, VP0699, and VP2979 to repress their transcription. These genes encode a group of proteins with GGDEF and/or EAL domains associated with c-di-GMP metabolism. CONCLUSION One of the mechanisms by which H-NS represses the biofilm formation by V. parahaemolyticus RIMD2210633 may be via repression of the production of intracellular c-di-GMP.
Bacterial Proteins/metabolism* ; Biofilms ; Cyclic GMP/analogs & derivatives* ; Gene Expression Regulation, Bacterial ; Gentian Violet ; Histones/metabolism* ; Vibrio parahaemolyticus/genetics*

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors