GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

Gastric cancer is a high-incidence malignancy that poses a serious threat to public health in China, ranking among the top three cancers in both incidence and mortality. The majority of patients are diagnosed at an advanced stage, resulting in limited treatment options and poor prognosis. To address key challenges in gastric cancer diagnosis and treatment, a research team led by Professor Jiafu Ji at Peking University Cancer Hospital has focused on the project "Development and Dissemination of Precision Medicine Approaches in Gastric Cancer Management". Through a series of high-quality multicenter clinical studies, the team established a set of new international standards in perioperative treatment, individua-lized drug selection, intelligent noninvasive diagnostics, and novel immunotherapy strategies. These advances have significantly improved treatment efficacy and reduced surgical trauma, achieving key technological breakthroughs in diagnosis, therapy, and mechanistic understanding, and systematically enhancing outcomes for gastric cancer patients. The project ' s findings had a broad international impact, including hosting China ' s first International Gastric Cancer Congress. Through nationwide dissemination, they have promoted the development of precision diagnosis and treatment of gastric cancer as a discipline, and led the formulation of the National Health Commission's guidelines for gastric cancer diagnosis and treatment. In recognition of its achievements, the project was awarded the First Prize of the 2024 Chinese Medical Science and Technology Award.
Stomach Neoplasms/genetics* ; Humans ; Precision Medicine/methods* ; China ; Immunotherapy/methods*

In recent years,the market share of food and medicine homology substances has continued to grow,and various types of contamination issues have become the focus of attention both inside and outside the industry.The contamination not only affects the original medicinal quality,but also leads to the accumulation of toxic substances in the human body,causing acute and chronic severe hazards such as vomiting,poisoning and cancer.Therefore,the development of biosensors that can conveniently,accurately and sensitively detect various pollutants in food and medicine homology substances has become a research hotspot.Aptasensors based on metal-organic frameworks(MOFs)with advantages such as strong specificity,rapid response and simple operation,have been widely used in detection of various pollutants.This review focused on the research progress of aptasensors based on MOFs for detection of food and medicine homology contamination in the past few years,and provided a detailed comparison and analysis for detection of chemical pollutants(such as pesticide residues,heavy metal residues,mycotoxins,etc.)and microbial contamination in food and medicine homology substances.Besides,the development trend and possible challenges of MOFs aptasensors in detection of food and medicine homology substances in the future were discussed,which was anticipated to provide a reference for the development of new MOFs aptasensors.

Objective:To investigate the short-term efficacy and safety of cardiac contractility modulation (CCM) in patients with heart failure.Methods:This was a cross-sectional study of patients with heart failure who underwent CCM placement at the First Affiliated Hospital of Xinjiang Medical University from February to June 2022. With a follow-up of 3 months, CCM sensation, impedance, percent output, and work time were monitored, and patients were compared with pre-and 3-month postoperative left ventricular ejection fraction (LVEF) values, and 6-minute walk test distance and New York Heart Association (NYHA) cardiac function classification, and the occurrence of complications was recorded.Results:CCM was successfully implanted in all 9 patients. Seven(7/9) of them were male, aged (56±14) years, 3 patients had ischaemic cardiomyopathy and 6 patients had dilated cardiomyopathy. At 3-month postoperative follow-up, threshold was stable, sense was significantly lower at follow-up than before (right ventricle: (16.3±7.0) mV vs. (8.2±1.1) mV, P<0.05; local sense: (15.7±4.9) mV vs. (6.7±2.5) mV, P<0.05), and impedance was significantly lower at follow-up than before (right ventricle (846±179) Ω vs. (470±65) Ω, P<0.05, local sense: (832±246) Ω vs. (464±63) Ω, P<0.05). The CCM output percentage was (86.9±10.7) %, the output amplitude was (6.7±0.4) V, and the daily operating time was (8.6±1.0) h. LVEF was elevated compared to preoperative ((29.4±5.2) % vs. (38.3±4.3) %, P<0.05), the 6-minute walk test was significantly longer than before ((96.8±66.7)m vs. (289.3±121.7)m, P<0.05). No significant increase in the number of NYHA Class Ⅲ-Ⅳ patients was seen (7/9 vs. 2/9, P>0.05). The patient was not re-hospitalised for worsening heart failure symptoms, had no malignant arrhythmic events and experienced significant relief of symptoms such as chest tightness and shortness of breath. No postoperative complications related to pocket hematoma, pocket infection and rupture, electrode detachment, valve function impairment, pericardial effusion, or cardiac perforation were found. Conclusions:CCM has better short-term safety and efficacy in patients with heart failure.

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.

Objective To understand the change in distribution and antimicrobial resistance of bacteria isolated from blood specimens of Hunan Province,and provide for the initial diagnosis and treatment of clinical bloodstream infection(BSI).Methods Data reported from member units of Hunan Province Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacterial antimicrobial resistance surveillance method was imple-mented according to the technical scheme of China Antimicrobial Resistance Surveillance System(CARSS).Bacteria from blood specimens and bacterial antimicrobial susceptibility testing results were analyzed by WHONET 5.6 soft-ware and SPSS 27.0 software.Results A total of 207 054 bacterial strains were isolated from blood specimens from member units in Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021,including 107 135(51.7％)Gram-positive bacteria and 99 919(48.3％)Gram-negative bacteria.There was no change in the top 6 pathogenic bacteria from 2012 to 2021,with Escherichia coli(n=51 537,24.9％)ranking first,followed by Staphylococcus epidermidis(n=29 115,14.1％),Staphylococcus aureus(n=17 402,8.4％),Klebsiella pneu-moniae(17 325,8.4％),Pseudomonas aeruginosa(n=4 010,1.9％)and Acinetobacter baumannii(n=3 598,1.7％).The detection rate of methicillin-resistant Staphylococcus aureus(MRSA)decreased from 30.3％in 2015 to 20.7％in 2021,while the detection rate of methicillin-resistant coagulase-negative Staphylococcus(MRCNS)showed an upward trend year by year(57.9％-66.8％).No Staphylococcus was found to be resistant to vancomy-cin,linezolid,and teicoplanin.Among Gram-negative bacteria,constituent ratios of Escherichia coli and Klebsiella pneumoniae were 43.9％-53.9％and 14.2％-19.5％,respectively,both showing an upward trend(both P＜0.001).Constituent ratios of Pseudomonas aeruginosa and Acinetobacter baumannii were 3.6％-5.1％and 3.0％-4.5％,respectively,both showing a downward trend year by year(both P＜0.001).From 2012 to 2021,resistance rates of Escherichia coli to imipenem and ertapenem were 1.0％-2.0％and 0.6％-1.1％,respectively;presenting a downward trend(P＜0.001).The resistant rates of Klebsiella pneumoniae to meropenem and ertapenem were 7.4％-13.7％and 4.8％-6.4％,respectively,presenting a downward trend(both P＜0.001).The resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenem antibiotics were 7.1％-15.6％and 34.7％-45.7％,respectively.The trend of resistance to carbapenem antibiotics was relatively stable,but has de-creased compared with 2012-2016.The resistance rates of Escherichia coli to the third-generation cephalosporins from 2012 to 2021 were 41.0％-65.4％,showing a downward trend year by year.Conclusion The constituent ra-tio of Gram-negative bacillus from blood specimens in Hunan Province has been increasing year by year,while the detection rate of carbapenem-resistant Gram-negative bacillus remained relatively stable in the past 5 years,and the detection rate of coagulase-negative Staphylococcus has shown a downward trend.

Objective To investigate changes in the distribution and antimicrobial resistance of bacteria isolated from cerebrospinal fluid(CSF)specimens in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021 were collected according to China Antimicrobial Resistance Surveillance Sys-tem(CARSS)technical scheme.Data of bacteria isolated from CSF specimens and antimicrobial susceptibility tes-ting results were analyzed with WHONET 5.6 and SPSS 20.0 software.Results A total of 11 837 bacterial strains were isolated from CSF specimens from member units of Hunan Province Antimicrobial Resistance Surveillance Sys-tem from 2012 to 2021.The top 5 strains were coagulase-negative Staphylococcus(n=6 397,54.0％),Acineto-bacter baumannii(n=764,6.5％),Staphylococcus aureus(n=606,5.1％),Enterococcus faecium(n=465,3.9％),and Escherichia coli(n=447,3.8％).The detection rates of methicillin-resistant coagulase-negative Staphyloco-ccus(MRCNS)and methicillin-resistant Staphylococcus aureus(MRSA)were 58.9％-66.3％and 34.4％-62.1％,respectively.No Staphylococcus spp.were found to be resistant to vancomycin,linezolid,and teicoplanin.The de-tection rate of Enterococcus faecium was higher than that of Enterococcus faecalis,and the resistance rates of En-terococcus f aecium to penicillin,ampicillin,high concentration streptomycin and levofloxacin were all higher than those of Enterococcus faecalis(all P=0.001).Resistance rate of Streptococcus pneumoniae to penicillin was 85.0％,at a high level.Resistance rate of Escherichia coli to ceftriaxone was＞60％,while resistance rates to enzyme inhibitors and carbapenem antibiotics were low.Resistance rate of Klebsiella pneumoniae to ceftriaxone was＞60％,to en-zyme inhibitors piperacillin/tazobactam and cefoperazone/sulbactam was＞30％,to carbapenem imipenem and me-ropenem was about 30％.Resistance rates of Acinetobacter baumannii to most tested antimicrobial agents were＞60％,to imipenem and meropenem were 59.0％-79.4％,to polymyxin B was low.Conclusion Among the bac-teria isolated from CSF specimens,coagulase-negative Staphylococcus accounts for the largest proportion,and the overall resistance of pathogenic bacteria is relatively serious.Bacterial antimicrobial resistance surveillance is very important for the effective treatment of central nerve system infection.

Objective To investigate the microstructural changes of temporal lobe epilepsy(TLE)in patients with sleep disorders based on diffusion kurtosis imaging(DKI).Methods This research prospectively included 38 TLE patients(case group)and 20 healthy controls(HC)(HC group).Participants used sleep questionnaires to evaluate their sleep status.All TLE patients were divided into groups with and without sleep disorders according to the diagnostic criteria and scale scores of sleep disorders.The mean kurtosis(MK),mean diffusivity(MD),and fractional anisotropy(FA)of the relevant region of interest(ROI)were measured by DKI sequence.The differences of sleep quality scores and DKI parameters between groups were further compared via independent samples t-test and one-way analysis of variance.Results The Epworth sleepiness scale(ESS),Athens insomnia scale(AIS),and Pittsburgh sleep qual-ity index(PSQI)scores of TLE patients with sleep disorders were significantly higher than those of HC group(P＜0.05).The FA and MK values in TLE patients were significantly lower than those in HC group,while the MD value of TLE patients were substan-tially higher than that of HC group(P＜0.05).The values of MK and FA in left TLE patients with sleep disorders were significantly lower than those of without sleep disorders(P＜0.05),while there was no significant difference in MD value between the two groups(P＞0.05).MK value of right TLE patients with sleep disor-ders was significantly lower than that of without sleep disorders(P＜0.05),however,there were no significant differences in MD and FA values between the two groups(P＞0.05).Conclusion Quantitative DKI analysis revealed differences in DKI parameters in TLE patients combined with sleep disorders,inferring a specific white matter fiber damage in this group and providing imaging data to support the personalized treatment and prognostic assessment of these patients.

Objective:To evaluate the efficacy of perioperative analgesia with esketamine in the patients undergoing thoracoscopic surgery.Methods:A total of 90 patients of either sex, aged 18-64 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for elective thoracoscopic lobectomy under general anesthesia, were divided into 3 groups ( n=30 each) by a random number table method: control group (C group) and different doses of esketamine groups (S 1 group, S 2 group). Before induction of anesthesia, esketamine 0.1 and 0.2 mg/kg were intravenously injected in S 1 group and S 2 group, respectively, while esketamine was not given in group C. Anesthesia was routinely induced in all the three groups. During anesthesia maintenance, esketamine 0.1 and 0.2 mg·kg -1·h -1 were intravenously infused in group S 1 and group S 2, respectively, and the remaining drugs used for anesthesia maintenance were the same in the three groups. Patient-controlled intravenous analgesia (PCIA) was used after operation, and PCIA solution contained sufentanil 2 μg/kg in group C, and esketamine 1 mg/kg was mixed on the basis as previously described in S 1 and S 2 groups. Aminotriol ketorolac was given as rescue analgesia to maintain numeric rating scale score at rest ≤3. The total amount of propofol and remifentanil during operation, effective pressing times of PCIA in postoperative 0-24 h and >24-48 h periods, and requirement for rescue analgesia were recorded. The occurrence of adverse reactions such as respiratory depression, nausea and vomiting, dizziness and salivation, and emergence time were recorded after surgery. The serum interleukin-6 (IL-6) concentration was measured by enzyme-linked immunosorbent assay at 30 min before and after surgery, and the malondialdehyde (MDA) concentration in serum was measured by thiobarbituric acid colorimetric analysis. The postoperative recovery was assessed using the 50-item quality of recovery scale at 1 and 2 days after surgery. The development of chronic pain was followed up by telephone within 1-3 months after surgery. Results:Compared with group C, the intraoperative consumption of remifentanil, effective pressing times of PCIA in postoperative 0-24 h and >24-48 h periods, rate of rescue analgesia, and postoperative serum IL-6 concentration were significantly decreased, and the 50-item quality of recovery scale score was increased in S 1 and S 2 groups, and the postoperative serum MDA concentration was significantly decreased in group S 2 ( P<0.05). Compared with group S 1, the consumption of intraoperative remifentanil was significantly decreased ( P<0.05), and no significant change was found in postoperative serum IL-6 and MDA concentrations in group S 2 ( P>0.05). Compared with group S 2, the postoperative emergence time was significantly shortened in S 1 and C groups ( P<0.05). There was no statistically significant difference in the intraoperative consumption of propofol, incidence of adverse effects and incidence of chronic pain among the three groups ( P>0.05). Conclusions:Esketamine for perioperative analgesia (dose before anesthesia induction 0.1 mg/kg, dose for maintenance of anesthesia 0.1 mg·kg -1·h -1, dose for postoperative PCIA 1 mg/kg) can raise the quality of analgesia and improve the quality of early postoperative recovery in the patients undergoing thoracoscopic lobectomy.

Rare diseases have a significant and profound impact on society, the economy, and the healthcare system. The path to developing drugs for rare diseases is particularly arduous. Due to the small number of patients and limited market demand, pharmaceutical companies don′t have enough incentives and resources to invest in drug research and development. Additionally, the long development cycles, high costs, and high risks have led to a number of potential therapeutic drug failures at the early stages of development. This article summarizes a series of encouraging policies adopted by the National Medical Products Administration for rare diseases, which is an important public health issue, as well as the achievements in the review and approval of rare disease drugs in recent years. These policies have accelerated the approval process. Meanwhile, the policies ensure the safety and effectiveness of drugs and offer more treatment options and hopes to patients with rare diseases. With the continuous effort at optimizing the policy environment and the advancement of research and development technologies, China′s drug regulatory authorities will continue to focus on the clinical needs of rare diseases, to implement " patient-centered " approach to drug development, inject new vitality into the research and development of drugs of rare diseases, and offer more precise and effective treatment choices for patients with rare diseases.