Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy. These subpopulations, e.g., cancer stem-like cells, cancer cells with epithelial-to-mesenchymal transition, and drug-tolerant persisters, are protected by their resistance traits at cellular and molecular levels. This review summarizes recent advances in the research on resistant populations and their resistance traits. NOTCH signaling, as a central regulator of nongenetic resistance, is discussed with a special focus on its canonical maintenance of resistant cancer cells and noncanonical regulation of their resistance traits. This novel view of canonical and noncanonical NOTCH signaling pathways is translated into our proposal of reshaping therapeutic strategies targeting NOTCH signaling in resistant cancer cells. We hope that this review will lead researchers to study the canonical and noncanonical arms of NOTCH signaling as an integrated resistant mechanism, thus promoting the development of innovative therapeutic strategies.
Neoplasms/metabolism* ; Receptors, Notch/metabolism* ; Disease Resistance/physiology* ; Signal Transduction/physiology* ; Humans ; Drug Resistance, Neoplasm/physiology* ; Molecular Targeted Therapy/methods*

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

OBJECTIVES: To explore the safety and effectiveness of arthroscopic reconstruction of coracoclavicular ligament by suspensory fixation to manage the acute acromioclavicular joint dislocation. METHODS: From January 2016 to December 2017, 18 cases of acute acromioclavicular joint dislocation were carried out with arthroscopic reconstruction of coracoclavicular ligament by double Endobutton plate suspensory fixation. Anteroposterior view X-ray plain radiographs were obtained on the second day, 6 months and 12 months after the surgery, MRI was performed in 1 year after operation. Meanwhile, subjective and objective scoring were obtained by Vsual Analogue Scale (VAS), Rating Scale of the American Shoulder and Elbow Surgeons (ASES) and University of California at Los Angeles Shoulder Rating Scale (UCLA). RESULTS: All patients were followed up for 12 to 30 months (an average of 18 months). There was no patient with infection, neurovascular injury, loosening and breakage of internal fixation, re-dislocation of acromioclavicular joint, clavicular fracture, coracoid process fracture, etc. Postoperative X-ray showed that all acromioclavicular joints were completely relocated. The follow-up of MRI after 1 year showed no obvious dislocation of acromioclavicular joint and good recovery of acromioclavicular space. Postoperative shoulder joint function, VAS, ASES, UCLA and acromioclavicular distance were significantly improved compared with those before surgery, with statistically significant differences (all <0.05). CONCLUSIONS Arthroscopic reconstruction of coracoclavicular ligament by suspensory fixation to manage the acute acromioclavicular joint dislocation has the advantages of minimal invasive, rapid functional recovery and less complications and satisfactory early clinical results.
Acromioclavicular Joint ; diagnostic imaging ; surgery ; Follow-Up Studies ; Humans ; Joint Dislocations ; diagnostic imaging ; surgery ; Magnetic Resonance Imaging ; Shoulder Dislocation ; diagnostic imaging ; surgery ; Treatment Outcome

Objective To explore the efficacy and safety of Polyethylene glycol 3350 plus electrolyte bulk on the schizophrenia patients with constipation induced by clozapine. Methods 150 cases of schizophrenia inpatient and outpatient with constipation induced by clozapine treatment were selected and randoly dirided into the group of polyethylene glycol,lactulose group and non-intervention group with 50 patients in each group and each patient or their families signed the informed consent. The treatment groups took orally with Polyethyle ne glycol 3350 plus electrolyte 13. 7grams,2 times per day and lactulose oral solution 10ml,3 times per day respectively. The non-intervention group was not given a regular basis laxatives, but with cathartic therapy in demand. The period of experiment was 6 weeks including 2 weeks baseline observation period and 4 weeks treatment. Assessment criteria: an overall assessment of all symptoms of patients and each patient's constipation and safety parameters were assessed. Results After treatment for 4 weeks,the total effective rate in three groups was 90.0% ,68.0% ,38.0% (all P ＜0.05). The difference was statistically significant. The normal shape of stool rate was 84.0% ,60.0% ,28.0%. PEG group were better than the other 2 groups at baseline in the first defecation time,the average times of bowel movements per week,theutilization of laxatives during treatment, while symptom score improvement in the stool was significantly better than other groups after treatment. The safety parameters including liver and kidney function, lectrolytes, glucose, ECG, symptoms of schizophrenia such as PANSS score had no obvious change in each group after treatment. Conclusion PEG 3350 plus electrolytes was effective and safe in the treatment of clozapine-indueed constipation in chronic schizophrenia.