The Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation is one of the most prevalent activating alterations in cancer. It indicates a poor overall prognosis due to its highly invasive nature. Although several KRAS inhibitors have been developed in recent years, a significant clinical challenge has emerged as a substantial proportion of patients eventually develop resistance to these therapies. Therefore, identifying determinants of drug resistance is critical for guiding treatment strategies. This review provides a comprehensive overview of the mutation landscape and molecular mechanisms of KRAS activity in various cancers. Meanwhile, it summaries the progress and prospects of small molecule KRAS inhibitors undergoing clinical trials. Furthemore, this review explores potential strategies to overcome drug resistance, with the ultimate goal of steering toward patient-centric precision oncology in the foreseeable future.
Humans ; Drug Resistance, Neoplasm/drug effects* ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Mutation/genetics* ; Neoplasms/genetics* ; Antineoplastic Agents/therapeutic use*

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

CD47 is an immune checkpoint widely regarded as a 'don't eat me' signal. CD47-based anti-cancer therapy has received considerable attention, with a significant number of clinical trials conducted. While anti-cancer therapies based on CD47 remain a focal point of interest among researchers, it is noteworthy that an increasing number of studies have found that CD47-based therapy ameliorated the pathological status of non-cancer diseases. This review aims to provide an overview of the recent progress in comprehending the role of CD47-based therapy in non-cancer diseases, including diseases of the circulatory system, nervous system, digestive system, and so on. Furthermore, we sought to delineate the promising mechanisms of CD47-based therapy in treating non-cancer diseases. Our findings suggest that CD47-based agents may exert their effect by regulating phagocytosis, regulating T cells, dendritic cells, and neutrophils, and regulating the secretion of cytokines and chemokines. Additionally, we put forward the orientation of further research to bring to light the potential of CD47 and its binding partners as a target in non-cancer diseases.

Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objectives:To analyze the status and temporal changes of disability-adjusted life year (DALY) for stomach and colorectal cancers among registered permanent residents in Changning District of Shanghai Municipality, and provide scientific basis for the prevention and treatment of stomach and colorectal cancers in this district.Methods:Using the cancer registration data of stomach and colorectal cancers from 2002 to 2019, we estimated the indices such as the DALYs, the DALY crude rates, the age-standardized DALY rates, etc. Then we used the Joinpoint regression model to calculate the average annual percent change (AAPC) and annual percent change (APC) to explore the temporal variations in different periods.Results:The DALYs of stomach and colorectal cancers in Changning District from 2002 to 2019 were 55 931 person years and 65 252 person years, respectively. The crude rates of DALY were 512.16/10 5 and 597.51/10 5, respectively. We observed a higher disease burden in men than in women, and the peak rate of DALY in stomach cancer was in the 75-79 years age group, while in colorectal cancer the rate was in the 85-years-or-older age group. Joinpoint regression analysis showed that from 2002 to 2019, the age-standardized DALY rate of stomach cancer showed a downward trend (AAPC=-3.86%, P＜0.05), while the trend of colorectal cancer was not statistically significant(AAPC=-0.08%, P＞0.05). However, the trends in the age-standardized DALY rates of colorectal cancer were different between males and females, with males showing an upward trend (AAPC=1.24%, P＜0.05) and females showing a downward trend (AAPC=-1.67%, P＜0.05). Conclusions:The DALY of stomach and colorectal cancers in Changning District of Shanghai showed a decreasing trend. Males and the middle-aged and elderly populations are still the key targets for disease prevention and control in this district.

Abrin,the most lethal plant-derived toxin known today,has attracted widespread attention from both the International Chemical Weapon Convention and the Biological and Toxin Weapons Convention.There is an urgent demand for the development of efficient detection and detoxification countermeasures against Abrin to adress its potential threats to human health and public safety.This review,based on clustering analysis of literature and on knowledge of the structures of various subtypes of Abrin,provides an overview of the analysis and detection techniques,the mechanism of toxicity,and detoxification countermeasures against Abrin.It concludes with an examination of the challenges and emerging trends in this field.The main analysis and detection techniques of Abrin include affinity-based analysis,physico-chemical-based analysis,and activity-based detection techniques.The challenges and developments in this field are also outlined.There is a pressing need to establish sensitive,specific,and accurate methods of measurement that are tailored to the structure and activity of Abrin in order to precisely assess and mitigate the toxin threat.Unfortunately,no effective antidotes have been deployed so far,with medical treatments confined to symptomatic care.Research and development of neutralizing antibodies remain stands as the most promising strategy for counteracting Abrin intoxication.

Objective:To explore the efficiency of radial collateral artery perforator flap to reconstruct defects of thumb web contracture release.Methods:The data of patients with moderate to severe thumb web contracture treated with radial collateral artery perforator flap from September 2018 to September 2022 in Department of Orthopedics-Hand Microsurgery of Xiangya Hospital, Central South University were analyzed retrospectively. A skin flap with the radial collateral artery perforating point as the center and the line connecting the deltoid muscle insertion point and the apex of the humeral lateral condyle as the axis were designed before surgery. During the operation, the skin scar in the thumb web area was first removed, and the contracted tissues such as deep fascia and muscles were loosened. Then, a skin flap was harvested along the design line and transferred to the recipient site. After vascular and nerve anastomosis under a microscope, the incision was intermittently sutured and a drainage tube was placed. The blood flow of the flap and complication were monitored closely. In the last follow-up, the distance and angle of thumb web were observed; the appearance, sensory recovery (excellent, good, moderate, and poor) and the hand function (S0 level to S4 level represented feeling no recovery to complete recovery) were evaluated.Results:A total of 8 patients were included, including 7 males and 1 female, aged 23-56 years (average of 40.3 years old). The distance of thumb web was 20-38 mm (average 26.9 mm), and the angle was 22°-36° (average 27.4°) before surgery. Five hands were classified as severe thumb web contracture, and 3 hands were moderate. The sizes of perforator flap were from 5.5 cm×3.5 cm-13.0 cm×6.5 cm. Seven flaps survived uneventfully and venous congestion occurred in 1 flap. After exploration, the flap survived completely. Primary healing of wounds occurred in the donor and recipient areas. Postoperative follow-up ranged from 6 months to 2.5 years (average 13.6 months). In the last follow-up, the distance of thumb web was 48-63 mm (average 57.1 mm), and the angle was 40°-52° (average 44.8°) post-operation. Thumb web function evaluation: excellent in 5 cases and good in 3 cases. All patients were satisfied with the thumb web. Sensory recovered to S3 in 3 cases, S2 in 4 cases and S1 in 1 case. The donor site healed well, leaving scars. There was no radial nerve damage, and elbow joint movement was normal.Conclusion:The radial collateral artery perforator flap has reliable blood supply, relatively simple operation and the appearance and function of thumb web restored well postoperatively. The application of radial collateral artery perforator flap is an effective procedure to repair the thumb web contracture.

Objectives:To analyze the status and temporal changes of disability-adjusted life year (DALY) for stomach and colorectal cancers among registered permanent residents in Changning District of Shanghai Municipality, and provide scientific basis for the prevention and treatment of stomach and colorectal cancers in this district.Methods:Using the cancer registration data of stomach and colorectal cancers from 2002 to 2019, we estimated the indices such as the DALYs, the DALY crude rates, the age-standardized DALY rates, etc. Then we used the Joinpoint regression model to calculate the average annual percent change (AAPC) and annual percent change (APC) to explore the temporal variations in different periods.Results:The DALYs of stomach and colorectal cancers in Changning District from 2002 to 2019 were 55 931 person years and 65 252 person years, respectively. The crude rates of DALY were 512.16/10 5 and 597.51/10 5, respectively. We observed a higher disease burden in men than in women, and the peak rate of DALY in stomach cancer was in the 75-79 years age group, while in colorectal cancer the rate was in the 85-years-or-older age group. Joinpoint regression analysis showed that from 2002 to 2019, the age-standardized DALY rate of stomach cancer showed a downward trend (AAPC=-3.86%, P＜0.05), while the trend of colorectal cancer was not statistically significant(AAPC=-0.08%, P＞0.05). However, the trends in the age-standardized DALY rates of colorectal cancer were different between males and females, with males showing an upward trend (AAPC=1.24%, P＜0.05) and females showing a downward trend (AAPC=-1.67%, P＜0.05). Conclusions:The DALY of stomach and colorectal cancers in Changning District of Shanghai showed a decreasing trend. Males and the middle-aged and elderly populations are still the key targets for disease prevention and control in this district.

Objective:To explore the efficiency of radial collateral artery perforator flap to reconstruct defects of thumb web contracture release.Methods:The data of patients with moderate to severe thumb web contracture treated with radial collateral artery perforator flap from September 2018 to September 2022 in Department of Orthopedics-Hand Microsurgery of Xiangya Hospital, Central South University were analyzed retrospectively. A skin flap with the radial collateral artery perforating point as the center and the line connecting the deltoid muscle insertion point and the apex of the humeral lateral condyle as the axis were designed before surgery. During the operation, the skin scar in the thumb web area was first removed, and the contracted tissues such as deep fascia and muscles were loosened. Then, a skin flap was harvested along the design line and transferred to the recipient site. After vascular and nerve anastomosis under a microscope, the incision was intermittently sutured and a drainage tube was placed. The blood flow of the flap and complication were monitored closely. In the last follow-up, the distance and angle of thumb web were observed; the appearance, sensory recovery (excellent, good, moderate, and poor) and the hand function (S0 level to S4 level represented feeling no recovery to complete recovery) were evaluated.Results:A total of 8 patients were included, including 7 males and 1 female, aged 23-56 years (average of 40.3 years old). The distance of thumb web was 20-38 mm (average 26.9 mm), and the angle was 22°-36° (average 27.4°) before surgery. Five hands were classified as severe thumb web contracture, and 3 hands were moderate. The sizes of perforator flap were from 5.5 cm×3.5 cm-13.0 cm×6.5 cm. Seven flaps survived uneventfully and venous congestion occurred in 1 flap. After exploration, the flap survived completely. Primary healing of wounds occurred in the donor and recipient areas. Postoperative follow-up ranged from 6 months to 2.5 years (average 13.6 months). In the last follow-up, the distance of thumb web was 48-63 mm (average 57.1 mm), and the angle was 40°-52° (average 44.8°) post-operation. Thumb web function evaluation: excellent in 5 cases and good in 3 cases. All patients were satisfied with the thumb web. Sensory recovered to S3 in 3 cases, S2 in 4 cases and S1 in 1 case. The donor site healed well, leaving scars. There was no radial nerve damage, and elbow joint movement was normal.Conclusion:The radial collateral artery perforator flap has reliable blood supply, relatively simple operation and the appearance and function of thumb web restored well postoperatively. The application of radial collateral artery perforator flap is an effective procedure to repair the thumb web contracture.