Pulmonary fibrosis(PF)is a chronic progressive lung disease caused by a variety of etiologies and is also a common outcome of various chronic inflammatory lung diseases.The incidence of pulmonary fibrosis is increasing year by year,with a high mortality rate that seriously threatens the life and health of patients.Although two drugs,pirfenidone and nintedanib,are already on the market for the treatment of pulmonary fibrosis,they can only slow down the progression of the disease but cannot reverse or stop the process of pulmonary fibrosis,and long-term use can produce a variety of adverse reactions.Therefore,it is highly necessary to develop new drugs for pulmonary fibrosis that are more targeted,effective,and well-tolerated by patients.The phosphatidylinositol-3-kinase(PI3K)signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis.Targeted inhibition of the PI3K signaling pathway may be an important direction for the development of new drugs for pulmonary fibrosis.At present,some PI3K signaling pathway inhibitors have shown good effects in preventing and treating pulmonary fibrosis,but most of them are still in the research stage.This article reviews the role of the PI3K signaling pathway in PF,further summarizes promising PI3K pathway inhibitors with PF therapeutic effects,including inhibitors in clinical trials and preclinical studies,and discusses their mechanisms of action and development prospects.

The synergistic antibacterial strategy of peroxidase mediated chemodynamic therapy(CDT)and photothermal therapy(PTT)has been proven to effectively resist bacteria.However,the antibacterial effect against Pseudomonas aeruginosa is severely limited due to the factors such as short lifespan of reactive oxygen species(ROS)(<200 ns)and limited diffusion distance(about 20?200 nm).In this study,glucopyranose functionalized MoO3-x(P-MoO3-x)nanoenzyme was successfully synthesized using a one-pot hydrothermal method.This nanoenzyme exhibited both peroxidase-like activity and a photothermal effect.The combined antibacterial performance and biological safety of P-MoO3-x was analyzed and verified.By utilizing specific interactions with glucopyranose and lectin,P-MoO3-x nanoenzyme could target the surface of Pseudomonas aeruginosa.This targeted approach effectively shortened the range of hydroxyl radicals,significantly enhancing the antibacterial effect against Pseudomonas aeruginosa.Under photothermal action,P-MoO3-x could reach the optimal reaction effect at 70℃.Even at low concentrations of hydrogen peroxide(50 μmol/L),it released more hydroxyl radicals.In vitro antibacterial analysis experiments demonstrated that the inactivation efficiency of the P-MoO3-x antibacterial system against Pseudomonas aeruginosa(106 CFU/mL)exceeded 99%.Furthermore,in vivo experiments confirmed the significant therapeutic effects of P-MoO3-x in treating methicillin-resistant Staphylococcus aureus(MRSA)infected wounds and promoting wound healing,without producing toxicity to cells.In conclusion,P-MoO3-x exhibited excellent antibacterial ability and good biocompatibility,making it a promising anti-infective nanoenzyme with broad application prospects.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Aim To investigate the regulatory mecha-nism of arrhythmia of sodium channel ubiquitination af-ter MI and to study the electrophysiological remodeling mechanism of lncRNA-CCRR after MI for the preven-tion and treatment of arrhythmia after MI.Methods LncRNA-CCRR transgenic mice and C57BL/6 mice injected with lncRNA-CCRR overexpressed adeno-asso-ciated virus were used.Four weeks after infection,the left anterior descending branch of the coronary artery was ligated for 12 h to establish a mouse acute myocar-dial infarction model,and the incidence of arrhythmia was detected by programmed electrical stimulation.Ln-cRNA-CCRR overexpression/knockdown adeno-associ-ated virus and negative control were transfected into neonatal mouse cardiomyocytes(NMCMs),and the model was prepared by hypoxia for 12 h.LncRNA-CCRR expression was detected by FISH,Nav1.5 and UBA6 protein and Nav.1.5 mRNA expression were de-tected by Western blot and real-time quantitative poly-merase chain reaction(qRT-PCR),Nav1.5 and UBA6 expressions were detected by immunofluores-cence,and the relationship between lncRNA-CCRR and UBA6 was detected by RIP.INa current density af-ter CCRR overexpression and knockdown was detected by Whole-cell clamp patch.Results In MI mice,the expression of lncRNA-CCRR decreased,the incidence of arrhythmia increased,the expression of CCRR and Nav1.5 mRNA was down-regulated,the protein ex-pression of Nav1.5 was down-regulated,and the pro-tein expression of UBA6 was up-regulated compared with sham group.Overexpression of CCRR could re-verse the above changes.AAV-CCRR could reverse the down-regulated CCRR and Nav1.5 mRNA levels af-ter hypoxia,and improve the expression of Nav1.5 and UBA6 protein.The direct relationship between ln-cRNA-CCRR and UBA6 was identified by RIP analy-sis.The INa density increased after transfection with AAV-CCRR.The INa density decreased after transfec-tion with AAV-si-CCRR.Conclusions The expres-sion of lncRNA-CCRR decreases after MI,and ln-cRNA-CCRR can improve arrhythmia induced by MI by inhibiting UBA6 to increase the protein expression level of Nav1.5 and the density of INa.

Analyzing the distribution characteristics of allergen sIgE in the serum of patients with respiratory and skin mucosal diseases in Shanghai City, and to provide epidemiological characteristics and diagnostic basis for the prevention and treatment of allergic respiratory and dermo-mucous diseases in Shanghai City. Adopting cross-sectional research, a total of 3 822 patients who received treatment in Tongren Hospital, Shanghai Jiao Tong University School of Medicine from July 2022 to July 2023 due to respiratory diseases or skin and dermo-mucous symptoms were included. Among them, there were 1 456 males and 2 366 females, with an age range of 1-97 years old. The median age (interquartile range) was 33 (27, 44) years old. The sIgE was detected by using immunoblotting. Statistical analysis was conducted using SPSS 22.0 software, and the comparison of count data (rates) between groups was conducted using χ 2 test. The results showed that a total of 3 377 (88.4%) cases among 3 822 patients were at least one allergen sIgE positive, and 72.9% (2 788/3 822) of them were multiple allergies sIgE positive. The top five allergen sIgE positive rates were Dermatophagoides pteronyssinus (37.9%, 1 447/3 822), Dermatophagoides farinae (32.1%, 1 225/3 822), milk (31.7%, 1 211/3 822), fungi (28.3%, 1 080/3 822), and Blomia tropicdis (23.8%, 909/3 822), with only milk was a kind of food allergen. The highest positive rates within the respiratory system disease group or dermo-mucous disease group were also these five allergens, without any difference in disease categories. The positive rates of cat dandruff, Humulusscandens, and juniper/birch in the respiratory system disease group were significantly higher than those in the skin and mucous membrane disease group, while the positive rates of shrimp/crab were relatively low (11.3% vs 14.9%, χ 2=9.616, P=0.002). Whether in the respiratory system disease group or the dermo-mucous disease group, the positive rates of Dermatophagoides pteronyssinus in male patients were significantly higher than those of females(42.6% vs 35.7%,41.0% vs 34.4%), with statistical significance ( χ 2=12.515, P<0.001; χ 2=5.143, P=0.023), And the three allergens, Dermatophagoides farinae, cat dander, and egg white allergens are also characterized by this feature.In addition, the positive rates of milk(33.8% vs 30.1%, χ 2=3.911, P=0.048), shrimp/crab(13.2% vs 10.0%, χ 2=6.423, P=0.014) in the respiratory system disease group were higher in males than in females, while in the dermo-mucous disease group, dog dander(20.5% vs 14.6%, χ 2=6.726, P=0.010) and peanuts/soybeans(10.5% vs 6.9%, χ 2=4.698, P=0.030) showed this phenomenon. In both the respiratory system disease group and the dermo-mucous disease group, there were 6 types of inhaled allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicdis, cat dandruff, dog dander, fungi) and 4 types of food allergens (egg yolks, egg white allergens, milk, shrimp/crab). However, the positivity rate of Aspergillus fumigatus (7.2% vs 9.3% vs 10.5% vs 15.7%, χ 2=10.996, P=0.012)in the respiratory disease group and cockroaches(4.2% vs 11.3% vs 9.6% vs 16.4%, χ 2=10.237, P=0.017) in the skin and mucosal disease group was the lowest in the underage group. There are seasonal differences in the positivity rates of allergens, with most allergens having significantly higher positivity rates in summer and autumn. In conclusion, the most common allergens sIgE positive in patients with respiratory and dermo-mucous diseases in Shanghai City are Dermatophagoides pteronyssinus, Dermatophagoides farinae, milk, fungi, and Blomia tropicdis. The trend of allergen sIgE prevalence in the two major categories of diseases is basically consistent. Allergen sIgE distribution varies among patient populations of different gender, age or season, and clinical prevention and treatment can be based on the results of serum allergen testing.

Analyzing the distribution characteristics of allergen sIgE in the serum of patients with respiratory and skin mucosal diseases in Shanghai City, and to provide epidemiological characteristics and diagnostic basis for the prevention and treatment of allergic respiratory and dermo-mucous diseases in Shanghai City. Adopting cross-sectional research, a total of 3 822 patients who received treatment in Tongren Hospital, Shanghai Jiao Tong University School of Medicine from July 2022 to July 2023 due to respiratory diseases or skin and dermo-mucous symptoms were included. Among them, there were 1 456 males and 2 366 females, with an age range of 1-97 years old. The median age (interquartile range) was 33 (27, 44) years old. The sIgE was detected by using immunoblotting. Statistical analysis was conducted using SPSS 22.0 software, and the comparison of count data (rates) between groups was conducted using χ 2 test. The results showed that a total of 3 377 (88.4%) cases among 3 822 patients were at least one allergen sIgE positive, and 72.9% (2 788/3 822) of them were multiple allergies sIgE positive. The top five allergen sIgE positive rates were Dermatophagoides pteronyssinus (37.9%, 1 447/3 822), Dermatophagoides farinae (32.1%, 1 225/3 822), milk (31.7%, 1 211/3 822), fungi (28.3%, 1 080/3 822), and Blomia tropicdis (23.8%, 909/3 822), with only milk was a kind of food allergen. The highest positive rates within the respiratory system disease group or dermo-mucous disease group were also these five allergens, without any difference in disease categories. The positive rates of cat dandruff, Humulusscandens, and juniper/birch in the respiratory system disease group were significantly higher than those in the skin and mucous membrane disease group, while the positive rates of shrimp/crab were relatively low (11.3% vs 14.9%, χ 2=9.616, P=0.002). Whether in the respiratory system disease group or the dermo-mucous disease group, the positive rates of Dermatophagoides pteronyssinus in male patients were significantly higher than those of females(42.6% vs 35.7%,41.0% vs 34.4%), with statistical significance ( χ 2=12.515, P<0.001; χ 2=5.143, P=0.023), And the three allergens, Dermatophagoides farinae, cat dander, and egg white allergens are also characterized by this feature.In addition, the positive rates of milk(33.8% vs 30.1%, χ 2=3.911, P=0.048), shrimp/crab(13.2% vs 10.0%, χ 2=6.423, P=0.014) in the respiratory system disease group were higher in males than in females, while in the dermo-mucous disease group, dog dander(20.5% vs 14.6%, χ 2=6.726, P=0.010) and peanuts/soybeans(10.5% vs 6.9%, χ 2=4.698, P=0.030) showed this phenomenon. In both the respiratory system disease group and the dermo-mucous disease group, there were 6 types of inhaled allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicdis, cat dandruff, dog dander, fungi) and 4 types of food allergens (egg yolks, egg white allergens, milk, shrimp/crab). However, the positivity rate of Aspergillus fumigatus (7.2% vs 9.3% vs 10.5% vs 15.7%, χ 2=10.996, P=0.012)in the respiratory disease group and cockroaches(4.2% vs 11.3% vs 9.6% vs 16.4%, χ 2=10.237, P=0.017) in the skin and mucosal disease group was the lowest in the underage group. There are seasonal differences in the positivity rates of allergens, with most allergens having significantly higher positivity rates in summer and autumn. In conclusion, the most common allergens sIgE positive in patients with respiratory and dermo-mucous diseases in Shanghai City are Dermatophagoides pteronyssinus, Dermatophagoides farinae, milk, fungi, and Blomia tropicdis. The trend of allergen sIgE prevalence in the two major categories of diseases is basically consistent. Allergen sIgE distribution varies among patient populations of different gender, age or season, and clinical prevention and treatment can be based on the results of serum allergen testing.

The taste of drugs has an important impact on the compliance of patients, but most of the active drug ingredients have an uncomfortable taste, especially traditional Chinese medicine. Through a variety of pharmaceutical excipients with taste masking properties combined with corresponding technologies can improve the taste of drugs and the characteristics of other dosage forms, so as to improve patient compliance. Here, we mainly summarize the auxiliary materials used for taste masking, explain the mechanism of taste masking from the point of view of excipients and introduces related uses, so as to provide reference for further research on taste masking of pediatric preparations.

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.
Humans ; Bacteremia/epidemiology* ; Cefoperazone ; Sulbactam ; Retrospective Studies ; Drug Resistance, Bacterial ; Microbial Sensitivity Tests ; Hematologic Neoplasms ; Sepsis ; Anti-Bacterial Agents/pharmacology* ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Piperacillin, Tazobactam Drug Combination ; Escherichia coli

ObjectivePeriprosthetic joint infections （PJI） are currently the most calamitous complication after arthroplasty. Although achievements have been made in many markers for the diagnosis of PJI， the lack of a gold standard remains a great obstacle for early diagnosis. This study aimed to investigate the association between coagulation markers and the development of PJI in patients undergoing revision total joint arthroplasty （TJA）. MethodsWe conducted a retrospective cohort study with a total of 2 517 patients who underwent hip or knee arthroplasties from January 2011 to January 2022 （2 394 with primary TJA， 87 with aseptic revision and 36 with PJI）. We applied univariate analysis and multivariate logistic regression to analyze differences of coagulation factors between primary TJA and aseptic revision or PJI group. Receiver operating characteristic （ROC） curve and area under the curve （AUC） were used to measure the diagnostic value of coagulation factors in predicting PJI. ResultsCoagulation factors and their ratios including plasma fibrinogen （FBG）， prothrombin time （PT）， thrombin time （TT）， activated partial thromboplastin time （APTT）， platelet （PLT）， mean platelet volume （MPV）， platelet distribution width （PDW）， plateletcrit （PCT）， PLT / MPV， PLT / PDW and PLT / PCT were included in this study. High FGB level was strongly correlated with the risk of PJI compared to other coagulation factors. The optimal threshold value of FBG was 4.53 g/L with a sensitivity of 47.22%， a specificity of 93.07% （Primary TJA group vs. PJI group）. Similarly， the optimal threshold value of FBG was 4.44 g/L with a sensitivity of 47.22%， a specificity of 95.40% between the other two groups （Aseptic revision group vs. PJI group）. ROC curve analysis demonstrated moderate diagnostic performance of FBG （AUC value）， indicating a potential to be a diagnostic marker for PJI. ConclusionsFBG is significantly correlated with PJI and it can be used as a potential non-invasive marker for early detection. It may serve as a safe and cost-effective tool for assessing PJI in clinical work.

OBJECTIVE: To analyze and compare the characteristics and causes of F wave changes in patients with Charcot-Marie-Tooth1A (CMT1A) and chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Thirty patients with CMT1A and 30 patients with CIDP were enrolled in Peking University Third Hospital from January 2012 to December 2018. Their clinical data, electrophysiological data(nerve conduction velocity, F wave and H reflex) and neurological function scores were recorded. Some patients underwent magnetic resonance imaging of brachial plexus and lumbar plexus, and the results were analyzed and compared. RESULTS: The average motor conduction velocity (MCV) of median nerve was (21.10±10.60) m/s in CMT1A and (31.52±12.46) m/s in CIDP. There was a significant difference between the two groups (t=-6.75, P < 0.001). About 43.3% (13/30) of the patients with CMT1A did not elicit F wave in ulnar nerve, which was significantly higher than that of the patients with CIDP (4/30, 13.3%), χ²=6.65, P=0.010. Among the patients who could elicit F wave, the latency of F wave in CMT1A group was (52.40±17.56) ms and that in CIDP group was (42.20±12.73) ms. There was a significant difference between the two groups (t=2.96, P=0.006). The occurrence rate of F wave in CMT1A group was 34.6%±39%, and that in CIDP group was 70.7%±15.2%. There was a significant difference between the two groups (t=-5.13, P < 0.001). The MCV of median nerve in a patient with anti neurofascin 155 (NF155) was 23.22 m/s, the latency of F wave was 62.9-70.7 ms, and the occurrence rate was 85%-95%. The proportion of brachial plexus and lumbar plexus thickening in CMT1A was 83.3% (5/6) and 85.7% (6/7), respectively. The proportion of brachial plexus and lumbar plexus thickening in the CIDP patients was only 25.0% (1/4, 2/8). The nerve roots of brachial plexus and lumbar plexus were significantly thickened in a patient with anti NF155 antibody. CONCLUSION The prolonged latency of F wave in patients with CMT1A reflects the homogenous changes in both proximal and distal peripheral nerves, which can be used as a method to differentiate the CIDP patients characterized by focal demyelinating pathology. Moreover, attention should be paid to differentiate it from the peripheral neuropathy caused by anti NF155 CIDP. Although F wave is often used as an indicator of proximal nerve injury, motor neuron excitability, anterior horn cells, and motor nerve myelin sheath lesions can affect its latency and occurrence rate. F wave abnormalities need to be comprehensively analyzed in combination with the etiology, other electrophysiological results, and MRI imaging.
Humans ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/pathology* ; Median Nerve/pathology* ; Ulnar Nerve/pathology* ; Brachial Plexus/pathology* ; Magnetic Resonance Imaging/methods*