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*

The gut microbiota is closely related to human health, and various gut microbiota health indices have been developed to assist in evaluating the health of the gut microbiota and even the overall health of the human body. Diets are one of the main factors that regulate the gut microbiota, while there is still no good method for evaluating the regulatory effects of dietary factors. To assess the regulatory effects of dietary factors on the gut microbiota of overweight individuals, we conducted an in vitro fermentation experiment based on 17 dietary factors, and developed an evaluation method for the regulatory effects of dietary factors based on the health index with principal component analysis (hiPCA). The results showed that most dietary factors had positive regulatory effects on the gut microbiota of overweight individuals. Galactooligosaccharides (GOS) and puerarin were the most significant dietary factors in regulating the gut microbiota of overweight individuals. The analysis of the contribution of species to the hiPCA indicated that GOS and puerarin might inhibit the activities of bacteria associated with overweight by regulating Eubacterium dolichum, Lactobacillus salivarius, Clostridium clostridioforme, Clostridium citroniae, and Lachnospiraceae bacterium 9_1_43BFAA. In addition, GOS may further enhance the inhibition of these activities by regulating Lachnospiraceae bacterium 6_1_63FAA, thereby reducing the gut health risks in overweight individuals. In summary, this study evaluated the health effects of dietary factors based on the hiPCA and specifically analyzed the role of different dietary factors in regulating the gut microbiota of overweight individuals. This provides new ideas and methods for improving gut microbiota health and has potential applications in the field of precision nutrition.
Humans ; Gastrointestinal Microbiome/physiology* ; Isoflavones/pharmacology* ; Overweight/microbiology* ; Diet ; Fermentation ; Oligosaccharides/pharmacology* ; Principal Component Analysis

The Xuming Decoction, which is recorded in the "Gu Jin Lu Yan" section of Zhang Zhongjing's Synopsis of the Golden Chamber, is a traditional Chinese medicine formula. Recent literature review and summary of the clinical application research progress have found that this formula is primarily used to treat diseases such as acute cerebral infarction, facial neuritis, multiple sclerosis, Guillain-Barre syndrome, and pulmonary distension. However, different medical practitioners and scholars hold diverse understandings of Xuming Decoction.

ObjectiveTo investigate the impact of acute respiratory infections in children under 12 years old in Pudong New Area， Shanghai from 2019 to 2023. MethodsAcute respiratory infection samples of children under 12 years old from three sentinel hospitals in Pudong New Area， Shanghai from 2019 to 2023 were collected， and 42 respiratory infection pathogens， including influenza virus， adenovirus， parainfluenza virus， respiratory syncytial virus， human enterovirus/rhinovirus， human pulmonary virus， human bokavirus， coronavirus （229E， HKU1， NL63 and OC43）， and novel coronavirus， were detected with microfluidic chips. The situation of acute respiratory infections among outpatient and inpatient children in this area was analyzed for the before the implementation of non pharmacological intervention measures （2019.12‒2020.1）， during the period of non pharmacological intervention measures （2020.2‒2022.12）， and after non pharmacological intervention measures （2023.1‒2023.6）. ResultsFrom 2019 to 2023， a total of 1 770 samples were collected， and 445 pathogens were detected， with a detection rate of 25.14% （445/1 770）. The main pathogens detected during the study period were influenza virus： 8.70% （154/1 770）， respiratory syncytial virus： 4.41% （78/1 770）， human enterovirus/rhinovirus： 2.66% （47/1 770）， human adenovirus： 2.49% （44/1 770）， and parainfluenza virus： 2.20% （39/1 770）. Before the implementation of non pharmacological intervention measures， outpatients were primarily infected with influenza， parainfluenza virus， and respiratory syncytial virus， with detection rates of 8.09%， 4.49%， and 4.04%， respectively； inpatients were mainly infected with influenza， respiratory syncytial virus， and parainfluenza virus， with detection rates of 4.49%， 3.82%， and 3.15%， respectively. During the period of non pharmacological intervention measures， influenza， rhinovirus and respiratory syncytial virus were the main viruses detected in the samples of outpatient children， with detection rates of 4.04%， 3.60%， and 2.47%， respectively； inpatient samples mainly detected respiratory syncytial virus， rhinovirus， and influenza virus， with detection rates of 3.60%， 2.02%， and 1.80%， respectively. After non pharmacological intervention measures， influenza， rhinovirus and respiratory syncytial virus were the main pathogens detected in the outpatients， with detection rates of 9.89%， 2.92% and 2.02%， respectively； influenza， respiratory syncytial virus， and rhinovirus were the main pathogens detected in inpatient children， with detection rates of 6.29%， 1.57%， and 1.35%， respectively. ConclusionThe prevalence of pathogens related to acute respiratory infections in children is influenced by non pharmacological preventive measures.

Objective:To observe and analyze the clinical and imaging features of eyes with cystoid macular degeneration (CMD) secondary to chronic central serous chorioretinopathy (cCSC).Methods:A retrospective clinical study. From February 2018 to June 2023, 9 patients of 15 eyes with cCSC secondary CMD diagnosed by ophthalmology examination in Yunnan University Affiliated Hospital were included in the study. All patients were male. The age was (53.67±3.83) years. The cases of binocular and monocular were 6 and 3 respectively. The visual acuity of the affected eye ranges from 0.02 to 0.1, which cannot be corrected. Visual acuity decreased and the duration of shadow occlusion was >1 year. Half dose photodynamic therapy (PDT) was performed on 8 eyes. All the patients underwent the best corrected visual acuity, posterior mydriatic fundus color photography, infrared fundus photography (IR), fundus autofluorescence (AF), fluorescein fundus angiography (FFA), optical coherence tomography (OCT), and multi-wavelength dazzling imaging (MC). The patients who received half dose PDT were followed up until 3 months after treatment. Patients who did not receive treatment were followed up to 2 years after the first diagnosis.Results:The light reflection in macular area decreased or disappeared in all eyes, and abnormal macular pigmentation was observed in 12 eyes. IR examination showed diffuse patchy weak fluorescence in the macular area in all affected eyes, and dotted strong fluorescence in the periphery. Fundus AF examination showed disc-like weak AF in the macular area, and scattered small amounts of strong AF in the middle and margins, among which the retinal pigment epithelium (RPE) atrophy trace in the macular area was observed in 7 eyes. By MC examination, the green signal in the macular area of the posterior pole of all affected eyes was uneven and mottled. FFA examination showed that no abnormal fluorescein leakage was observed in 15 eyes and 8 eyes showed strong fluorescence caused by diffuse permeation fluorescence. A small amount of active fluorescein was found in 7 eyes. OCT examination showed that there were several cystic cavities of different sizes in all the affected eyes, RPE atrophied to different degrees, and RPE cell compensatory ridges and tubular structures in the outer retina were seen in 6 eyes; 7 eyes with CMD and active leakage showed signs of subcortical fluid accumulation. Choroidal hypertrophy was seen in all affected eyes, with significant expansion of the great vascular layer and compression of the middle vascular layer and capillary layer. In 8 eyes treated with half-dose PDT, 6 eyes were ineffective at 3 months after treatment. The treatment was effective in 2 eyes. In 7 eyes that did not receive half-dose PDT, CMD structure did not improve significantly after 2 years of follow-up. The visual acuity decreased with the prolongation of the disease.Conclusions:CMD is more common in cCSC with a long course of disease, which has significant effects on vision and poor prognosis. Fundus color photography shows that the reflection in the macular area of the pole is weakened or disappeared, which may be combined with macular abnormal pigmentation. IR and AF examination show uneven fluorescence in macular area. The green signal in macular area is not uniform according to MC inspection. FFA shows strong fluorescence caused by diffuse permeable fluorescence and fluorescein leakage in active lesions. OCT examination shows that multiple small sacs or connections between sacs were broken and fused, and RPE atrophied to varying degrees.

Objective:To observe the clinical features of collateral circulation in different types of retinal vein occlusion.Methods:A retrospective clinical study. A total of 360 patients with monocular retinal vein occlusion diagnosed by ophthalmic examination in Department of Ophthalmology of Yunnan University Affiliated Hospital from December 2021 to December 2023 were included in the study. Among them, 157 males had 157 eyes and 203 females had 203 eyes. Age were (61.0±5.9) years. The duration of the disease from the onset of symptoms to the time of treatment was 3 days to 6 months. Macular branch vein occlusion (MBRVO), retinal branch vein occlusion (BRVO) and central retinal vein occlusion (CRVO) were observed in 67, 187 and 106 eyes, respectively. 210 eyes were with macular edema. All patients with macular edema were treated with anti-vascular endothelial growth factor (VEGF) by intravitreal injection. All eyes were examined by scanning source optical coherence tomography. The incidence, location, morphological characteristics, formation time of retinal collateral circulation and the effect of anti-VEGF drug on the formation of collateral circulation were observed. A short circuit in which blood vessels originating from the optic disc in the form of a blood loop return to the optic disc after the disc has been deformed for some time is defined as a short-circuited collateral circulation of the ciliary vessels of the optic disc.Results:After 1 week of disease course, MBRVO and collateral circulation of BRVO affected eye were established. By 1 to 2 months, a relatively abundant and stable collateral circulation had been established. In the course of 2 to 3 months, the short-circuit collateral circulation of ciliary vessels in the optic disc of the affected eye gradually formed. At 6 months, collateral circulation was established in 36 eyes (53.7%, 36/67) in 67 MBRVO patients. Collateral circulation was observed in 187 eyes of BRVO patients (100.0%, 187/187). In 106 eyes with CRVO, collateral circulation was established in 29 eyes (18.1%, 29/106). In 36 eyes with MBRVO, collateral circulation was established at the vertical horizontal slit between the blocked area and the non-blocked area. In 187 eyes of BRVO patients, collateral circulation was established in the vertical horizontal slit between the blocked and non-blocked areas in 102 eyes; 54 eyes were blocked the most central bypass to the collateral circulation on normal blood vessels. The collateral circulation of 19 eyes was established through nasal and temporal side. Collateral circulation through the fovea was established in 12 eyes. Its morphology is straight out of shape, spiral sinuous and flower cluster. CRVO established collateral circulation in 29 eyes, all of which had short-circuit collateral circulation of ciliary vessels. In 210 eyes treated with anti-VEGF drugs, collateral circulation was established in 160 eyes. Among them, 32 eyes were MBRVO (50.7%, 32/63), BRVO 119 eyes (100.0%, 119/119), CRVO 9 eyes (32.1%, 9/28).Conclusions:The incidence of collateral circulation of MBRVO, BRVO and CRVO is 53.7%, 100.0% and 18.1%, respectively. The forms of MBRVO were varied and the course of disease is about 2 months. Anti-VEGF therapy did not inhibit the establishment of collateral circulation.

Objective:To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE).Methods:Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children′s Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children′s characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed.Results:Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications.Conclusions:The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.

The dental operative microscope has been widely employed in the field of dentistry, particularly in endodontics and operative dentistry, resulting in significant advancements in the effectiveness of root canal therapy, endodontic surgery, and dental restoration. However, the improper use of this microscope continues to be common in clinical settings, primarily due to operators' insufficient understanding and proficiency in both the features and established operating procedures of this equipment. In October 2019, Professor Jingping Liang, Vice Chairman of the Society of Cariology and Endodontology, Chinese Stomatological Association, organized a consensus meeting with Chinese experts in endodontics and operative dentistry. The objective of this meeting was to establish a standard operation procedure for the dental operative microscope. Subsequently, a consensus was reached and officially issued. Over the span of about four years, the content of this consensus has been further developed and improved through practical experience.
Humans ; Dentistry, Operative ; Consensus ; Endodontics ; Root Canal Therapy ; Dental Care

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.

Objective:To search and summarize the literature in the field of joint replacement tele-rehabilitation at home and abroad and carry out visual analysis to discuss the development status, research hotspots and development trends in this field.Methods:Based on the Web of Science index database, literature related to application of tele-rehabilitation in joint replacement was searched from the establishment of the database to December 31, 2022. The literature metrology and knowledge visualization analysis of tele-rehabilitation after joint replacement were carried out by using the cooperative network and co-occurrence network analysis function of CiteSpace visual analysis tool and the result analysis report of Web of Science database.Results:As of December 2022, a total of 1 042 articles were published on research related to remote rehabilitation after joint replacement surgery, with an increasing number of articles published year by year. From 2020 to 2022, the annual number of articles published exceeded 100. The United States ranked first in both the number of articles published (404) and the H-index (44). The journal with the highest publication volume was Journal of Arthroplasty (106 articles), and the author with the highest publication volume was Mont (22 articles). Research hotspots focused on rehabilitation content, outcome evaluation and intervention implementation forms. Conclusions:The application of tele-rehabilitation in the field of joint replacement is becoming increasingly widespread. Foreign countries have started this research field early, while China is still in its infancy, and it is urgent to enrich the implementation of intervention forms, feasibility and effectiveness evaluation. The content optimization of tele-rehabilitation program, the accurate evaluation of curative effect and the optimization of implementation approach are the future research hotspots, and the study of cost effectiveness of tele-rehabilitation is the future research direction.