Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.

Objective:To evaluate the optimization efficacy of pressure-volume (P-V) curve-based individualized lung-protective ventilation strategy combined with pressure-controlled ventilation-volume guaranteed (PCV-VG) mode (LPVS+ PCV-VG) for one-lung ventilation (OLV) in elderly patients undergoing radical resection of lung cancer.Methods:Seventy American Society of Anesthesiologists Physical Status classificationⅡ-Ⅲ patients, aged 65-74 yr, with body mass index of 18-24 kg/m 2, undergoing elective thoracoscopic radical resection of lung cancer, were divided into 2 groups ( n=35 each) using a random number table method: PCV-VG group and LPVS+ PCV-VG group. Blood samples were collected from the radial artery for blood gas analysis before induction of general anesthesia (T 0), at 5 min of two lung ventilation after endotracheal intubation (T 1), at 30 min of OLV (T 2), at the end of OLV (T 3), and at 5 min of two lung ventilation in supine position (T 4). Ppeak, mean airway pressure (Pmean) and dynamic lung compliance (Cdyn) were recorded. The use of antibiotics, lung-related complications and rehabilitation were recorded within 7 days after operation. Results:Compared with PCV-VG group, PaO 2, PaCO 2 and Cdyn were significantly increased at T 2-4, Ppeak was decreased at T 2, 3, Pmean was increased at T 3, the requirement for antibiotics within 7 days after operation was decreased, the incidence of 1 grade lung-related complications was decreased, and the thoracic drainage tube indwelling time and length of hospital stay were shortened in LPVS+ PCV-VG group ( P<0.05). Conclusions:Individualized LPVS based on P-V curve combined with PCV-VG mode provides better efficacy for OLV in elderly patients undergoing radical resection of lung cancer.

Aged ; Antiviral Agents/therapeutic use* ; COVID-19/drug therapy* ; China/epidemiology* ; Cohort Studies ; Female ; Hospital Mortality ; Hospitalization ; Humans ; Male ; Middle Aged ; Patient Acuity ; SARS-CoV-2 ; Treatment Outcome

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*

Objective:To develop a model of stellate ganglion block (SGB) in mice and investigate the effect of SGB on cerebral cortical blood flow.Methods:Thirty clean-grade healthy male C57BL/6 mice, aged 8-9 weeks, weighing 23-27 g, were divided into 5 groups ( n=6 each) using a random number table method: control group (group C), left SGB group (group L), left normal saline group (group SL), right SGB group (group R) and right normal saline group (group SR). Group C received no intervention.SGB was performed with 0.25% ropivacaine 0.08 ml via percutaneous posterior approach in L and R groups, while the equal volume of normal saline 0.08 ml was given instead at the location of left and right stellate ganglion in SL and SR groups, respectively.The cerebral cortical blood flow was determined using laser speckle contrast imaging system before SGB (T 0) and at 10, 30, 60, 90 and 120 min after SGB (T 1-5). Results:Mice developed ptosis on the block side, indicating that the model of SGB was successfully developed in L and R groups.There was no significant difference in cerebral cortical blood flow at each time point among C, SL and SR groups ( P>0.05), and cerebral cortical blood flow on the block side decreased at T 1, began to increase at T 2, peaked at T 3, and decreased at T 5 which was still higher than that at T 0 in group L and group R ( P<0.01). Compared with C and SL groups, the left cerebral cortical blood flow was significantly decreased at T 1, 5 and increased at T 2-4 in group L ( P<0.01). Compared with C and SR groups, the right cerebral cortical blood flow was significantly decreased at T 1, 5 and increased at T 2-4 in group R ( P<0.01). There were no significant differences in cerebral cortical blood flow at each time point between group C and group SL and between group C and group RL ( P>0.05). Conclusions:The mouse model of SGB via percutaneous posterior approach is successfully developed.Unilateral SGB can affect cerebral cortical blood flow on the block side, which shows a transitory decrease followed by a sustained significant increase.

Objective:To evaluate the effect of age on mood of patients during induction of general anesthesia with remimazolam.Methods:Eighty American Society of Anesthesiologists physical status Ⅰ or Ⅱpatients of both sexes, undergoing elective surgery with general anesthesia requiring tracheal intubation, aged 5-80 yr, with body mass index 18-30 kg/m 2, were divided into 4 groups ( n=20 each) according to different ages: juvenile group (R 1 group, 5-17 yr), youth group (R 2 group, 18-44 yr), middle-aged group (R 3 group, 45-59 yr) and elderly group (R 4 group, 60-80 yr). Remimazolam was intravenously injected in a loading dose of 0.1 mg/kg for induction of general anesthesia, followed by an infusion of 0.1 mg·kg -1·h -1 for maintenance of general anesthesia, and the other anesthetics for induction and maintenance of anesthesia were all the same in each group.The changes in emotion and brain wave within 3 min after remimazolam injection were recorded.The brain waves and Modified Observer′s Assessment of Alertness and Sedation (MOAA/S) scale score were recorded at 1, 2 and 3 min after administration.Adverse effects during anesthesia induction were also recorded. Results:Compared with group R 1, the incidence of happy mood was significantly decreased, the grade of mood was decreased, and the dream Likert score and MOAA/S score were decreased in R 3 and R 4 groups, and the dream Likert score and MOAA/S score were decreased in group R 2, and the incidence of hypoxemia during induction of general anesthesia was increased in group R 4( P<0.01). Compared with group R 2, the incidence of happy mood was significantly decreased in R 3 and R 4 groups, and MOAA/S score was significantly decreased in group R 4 ( P<0.05). Compared with R 1 and R 2 groups, the proportion of beta bands was significantly decreased, and the proportion of theta and delta bands was increased in R 3 and R 4 groups ( P<0.01). Compared with group R 3, the proportion of beta band was significantly decreased, and the proportion of delta band was increased in group R 4 ( P<0.01). Conclusion:Remimazolam 0.1 mg/kg used for induction of general anesthesia can cause happy mood, accompanied by enhanced brain electrical signal activity of beta band, especially in the patients under 45 yr of age.