The mutual learning between Chinese and Western civilizations today provides a broad perspective and new opportunity for the development of traditional Chinese medicine （TCM）， fostering the interdisciplinary integration， fusion， and innovation of the discipline. The premise of mutual understanding of civilizations is uphold the principles of Chinese traditional scholarship and original thinking， overcome academic barriers and cognitive differences， and achieve the organic integration of knowledge systems and research methods. The development of TCM as a discipline should first be based on literature as a carrier to convey ideas and ensure the continuity of the academic tradition. Secondly， the discipline development should be guided by the unique， original thinking of TCM， accurately identifying the bottlenecks in its development， focusing on the key links for improvement， continuously exploring innovative academic paths， and striving to build a leading research platform. Finally， the cultivation of talents in the field of TCM discipline should focus on leading ones with international academic discourse power and influence， and establish an academic team with clinical thinking and interdisciplinary knowledge structure.

Objective To investigate the preventive effects of lidocaine administered through different routes on cardiovascular stress responses during anesthesia tracheal intubation. Methods Total 120 patients scheduled for elective surgery under general anesthesia were randomly divided into three groups: intravenous injection group （group IV）, throat spray group （group LJ）, and control group （group CT）, with 40 patients in each. Group IV received 50 mg of lidocaine via intravenous injection 1 minute before tracheal intubation. Group LJ received 50 mg of lidocaine sprayed into the pharyngeal cavity, glottis, and subglottic area. Group CT did not receive any treatment, and the remaining procedures were performed following the routine general anesthesia induction protocol. Heart rate （HR）, systolic blood pressure （SBP）, diastolic blood pressure （DBP）, and mean arterial pressure （MAP） were recorded at four time points: T₀ （before tracheal intubation）, T₁ （immediately after tracheal intubation）, T₂ （3 minutes after intubation）, and T₃ （5 minutes after intubation）. Statistical analysis of the data was performed using SPSS 22.0. Results There were no significant differences in HR at various time points within the group LJ. The changes in HR in the group IV and group CT were different statistically from those in the throat spray group. The blood pressure of patients in all three groups increased to varying degrees immediately after tracheal intubation, with the group CT showing particularly significant changes that differed significantly from both the group IV and the group LJ. The group LJ rapidly returned to levels close to those before intubation. Conclusion The preventive effects of lidocaine on stress responses during tracheal intubation were different depending on the route of administration. The inhibitory preventive effect of the throat spray method was superior to that of intravenous lidocaine, especially in preventing changes in heart rate.

Objective The aim of this study was to characterize the basic molecular and biochemical parameters for a cyclophilin protein in Cryptosporidium parvum called CpCyP1.Methods CpCyP1 expression patterns during the parasite life cycle were evaluated using qRT-PCR with total RNA isolated from different developmental stages of C.parvum.Native CpCyP1 protein in sporozoites was detected using western blot.The localization of CpCyP1 was performed using the immunofluorescence assay,with an affinity-purified rabbit polyclonal antibody against a synthetic peptide.The peptidyl-prolyl cis-trans isomerase(PPIase)activity of His-tagged recombinant CpCyP1 was evaluated using absorbance colorimetry,and the effect of cyclosporin A(CsA)on the activity of CpCyP1 was determined.Results CpCyP1 was expressed in all parasite developmental stages,whereas CpCyP1 was present mainly in the cytosol of sporozoites,meronts,and gamonts.CpCyP1 displayed Michaelis-Menten kinetics towards N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide for its PPIase activity(Km=456.4 μmol/L;Vmax=1.981 U).CsA inhibited PPIase activity,showing lower micromolar inhibitory activity and binding affinity(Kd=5.122 μmol/L;IC50=1.004 μmol/L).Conclusions These results imply that CpCyP1 in the parasite may be the target for the previously reported anti-cryptosporidial efficacy of CsA and suggest that C.parvum cyclophilins could be evaluated as candidate drug targets.

Objective:To investigate the differences of the glymphatic system (GS) function between patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and healthy controls and between different seizure types by using diffusion tensor imaging along perivascular space (DTI-ALPS), and to analyze the correlation between GS function and the course of disease, as well as the efficacy of predicting the surgical outcome.Methods:This study was a cross-sectional study. A total of 171 patients with mTLE-HS (mTLE-HS group) and 75 healthy volunteers (HC group) were retrospectively enrolled from July 2009 to July 2021 at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University. The general information of all subjects, such as seizure type (partial seizure, secondary generalized seizure), surgical outcome, etc., was analyzed. The 3D magnetization prepared rapid gradient echo T 1WI and DTI sequence images were collected. The VBM analysis method was used to segment cerebrospinal fluid and calculate the volume. The ALPS index of the bilateral brain was calculated using the Atlas-based DTI-ALPS method. Independent sample t-test or paired t test were used to compare the ALPS index between the mTLE-HS group and HC group, and between patients with different seizure types. Pearson correlation analysis was used to analyze the correlation between bilateral ALPS index and disease duration in mTLE-HS group. The predictive value of the ALPS index for surgical outcomes was evaluated by receiver operating characteristics curve and area under the curve. Results:Among the 171 mTLE-HS patients, 98 patients were mTLE with left-side HS (mTLE-LHS) and 73 patients were mTLE with right-side HS (mTLE-RHS); 37 patients underwent surgical treatment, including 27 with good prognosis and 10 with poor prognosis. Compared with the HC group, the left-side ALPS index of mTLE-LHS and mTLE-RHS were both decreased ( P<0.05). The right-side ALPS index in mTLE-RHS was lower than that in the HC group ( P<0.001). There was no significant difference in the right-side ALPS index between mTLE-LHS and HC group ( P=0.080). The ALPS index on the affected side of patients with secondary generalized seizures was significantly lower than that of patients with only partial seizures (all P<0.05), but the difference in ALPS index on the healthy side was not statistically significant( P>0.05). The left-side and right-side ALPS index in mTLE-LHS were negatively correlated with disease duration ( r=-0.272, P=0.007; r=-0.307, P=0.002), but no significant correlation was found between the left-side or right-side ALPS index in mTLE-RHS (all P>0.05). The DTI-ALPS index on the affected side in mTLE-HS patients exhibited good diagnostic accuracy for surgical outcome classification, with an area under the curve of 0.778. Conclusions:The patients with mTLE-HS exhibit dysfunction of the GS, and the degree of impairment is related to the type of seizure and the course of epilepsy. The ALPS index, which characterizes the function of GS, demonstrates good diagnostic accuracy for classifying surgical outcomes.

Objective:To evaluate the clinical efficacy of botulinum toxin type A (BTX-A) combined with sodium hyaluronate solution for facial microdroplet injection in improving facial skin photoaging.Methods:A prospective randomized controlled trial was conducted. From January to July 2024, patients with facial photoaging problems were recruited from the Plastic Surgery Department of the Affiliated Hospital of Xuzhou Medical University and randomly divided into a monotherapy group (sodium hyaluronate solution droplet injection) and a combination therapy group (BTX-A + sodium hyaluronate solution droplet injection) by hierarchical block randomization method. The treatment regimen was 3 months, with one treatment for each month, with a total of 3 treatment. The combination therapy group only used a combination therapy of two drugs (BTX-A 25 U+ 5 ml sodium hyaluronate solution) during the first injection. During the three treatments of the monotherapy group and the second and third treatments of the combination therapy group, 5 ml of sodium hyaluronate solution was injected as the solo ingredient. Follow up was conducted at 1, 2, and 4 months after the last treatment. Serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were detected by test kit. Five skin texture indicators (moisture content, transepidermal water loss rate, elasticity, glossiness, and pH) were evaluated using the German CK skin tester. VISIA skin detector was used for facial two-dimensional photography and skin condition analysis. Clinical efficacy (significant improvement, obvious improvement, improvement, no improvement) and global aesthetic improvement scale (GAIS) scores on a 5-point scale were recorded. Patient satisfaction levels (very satisfied, satisfied, and dissatisfied) were investigated. The data were analyzed using SPSS 27.0 software. Count data was presented as examples and(or) percentages, and analyzed using a chi-square test. Normal distribution measurement data was represented by Mean±SD and analyzed using t-test. Results:A total of 100 patients were included, with 50 cases in each group. There were 17 males and 33 females in the monotherapy group, with an age of (31.3±7.1) years, and there were 5, 14, 29 and 2 patients in the Ⅰ to Ⅳ types of Glogau skin photoaging classification, respectively. There were 15 males and 35 females in the combination therapy group, with an age of (32.1±8.4) years old, and there were 4, 15, 27 and 4 patients in the Ⅰ to Ⅳ types of Glogau skin photoaging classification, respectively. There was no statistically significant difference in gender composition, age, and Glogau skin photoaging classification between the two groups (all P>0.05). One month after the first treatment, both groups showed an increase in SOD activity and a decrease in MDA levels, with more significant changes observed in the combination therapy group ( P<0.01 for both). At the follow-up of 1, 2, and 4 months after the last treatment, the combination therapy group outperformed the monotherapy group in all 5 skin texture indicators (all P<0.05). One month after the last treatment, the total effective rate of the combination therapy group was 76.0% (38/50), which were significantly higher than that of the monotherapy group’s 50.0% (25/50) ( P<0.05); in addition, the combination therapy group showed significant advantages in facial aesthetic GAIS scores, as well as patient satisfaction, with a satisfaction rate of up to 98.0% (49/50), which was higher than the 88.0% (44/50) of the monotherapy group ( P<0.01). Throughout the entire treatment process, neither group experienced serious adverse reactions. Conclusion:Facial microdroplet injection of BTX-A combined with sodium hyaluronate solution effectively improves symptoms of facial skin photoaging, enhancing skin hydration and elasticity, reducing transepidermal water loss, improving skin gloss, regulating skin pH, and enhancing skin antioxidant capacity, ultimately achieving facial skin rejuvenation. This method is safe, effective and holds high clinical relevence and patient satisfaction.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in eukaryotes, with nearly 800 genes coding for these proteins. They are involved in many physiological processes, such as light perception, taste and smell, neurotransmitter, metabolism, endocrine and exocrine, cell growth and migration. Importantly, GPCRs and their ligands are the targets of approximately one third of all marketed drugs. GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane. However, emerging evidence suggests that GPCRs are also localized on mitochondria, where they play critical roles in modulating mitochondrial functions. These mitochondrial GPCRs (mGPCRs) can influence processes such as mitochondrial respiration, apoptosis, and reactive oxygen species (ROS) production. By interacting with mitochondrial signaling pathways, mGPCRs contribute to the regulation of energy metabolism and cell survival. Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling, highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction. This expanding understanding of mGPCR function on mitochondria opens new avenues for research, particularly in the context of diseases where mitochondrial dysfunction plays a key role. Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease, diabetes, obesity and Alzheimer's disease. In this review, we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases. We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease, and to underscore their potential as therapeutic targets in the treatment of these conditions.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy. METHODS: To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated. RESULTS: OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression. CONCLUSION Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans ; ErbB Receptors/metabolism* ; Mouth Neoplasms/metabolism* ; Cell Line, Tumor ; Animals ; Drug Resistance, Neoplasm/genetics* ; Cadherins/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Mutation/genetics* ; Mice, Nude ; Protein Kinase Inhibitors/therapeutic use* ; Cetuximab/pharmacology* ; Afatinib/therapeutic use* ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects*