Severe pneumonia is one of the most common and critical respiratory diseases in clinical practice. It is characterized by rapid progression， difficult treatment， high mortality， and many complications， posing a significant threat to the life and health of patients. The pathogenesis of severe pneumonia is highly complex， and studies have shown that its occurrence and development are closely related to multiple signaling pathways. Currently， the treatment of severe pneumonia mainly focuses on anti-infection， mechanical ventilation， and glucocorticoids， but clinical outcomes are often not ideal. Therefore， finding safe and effective alternative therapies is particularly important. In recent years， with the deepening of research into traditional Chinese medicine （TCM）， it has gained widespread attention in the treatment of severe pneumonia. This paper reviewed the relationship between severe pneumonia and relevant signaling pathways in recent years and how TCM regulated these pathways in the treatment of severe pneumonia. It was found that TCM could regulate the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， NOD-like receptor protein 3 （NLRP3）， and nuclear factor E₂-related factor 2 （Nrf2） signaling pathways， playing a role in reducing the inflammatory response， inhibiting cell apoptosis and pyroptosis， improving oxidative stress， and other effects in the treatment of severe pneumonia. Among these pathways， it was found that all of them regulated inflammation to treat severe pneumonia. Therefore， reducing inflammation is the core mechanism by which Chinese medicine treats severe pneumonia. This review provides direction for the clinical treatment of severe pneumonia and offers a scientific basis for the research and development of new drugs.

Objective To develop and validate a scoring system to predict the possibility of laparoscopic cholecystectomy (LC) conversion to laparotomy based on preoperative clinical data, and to establish a grading management model of surgery. Methods A retrospective analysis was conducted on the clinical data of 9 414 patients who underwent LC at Renhe Hospital and Huashan Hospital from June 2013 to June 2018. The patients were divided into two groups: the LC group (9 246 patients who successfully underwent LC) and the conversion to laparotomy group (168 patients who required conversion to open surgery). The data of two groups were compared, and the risk factors affecting conversion to laparotomy were screened out by single factor analysis of Chi-square test. Then, the risk factors were analyzed by multiple Logistic regression, and the pre-coefficient of each variable of the risk factors was assigned according to the established conversion to laparotomy possibility function. After calculating the score of each case, the difference in the actual conversion rate of each group was compared. The area under receiver operating characteristic (ROC) curve was calculated to evaluate the performance of the scoring system. According to the scoring system, LC surgical grading management model was created and verified. Results The following factors were identified as significant risk factors for conversion to laparotomy (P < 0.001): body temperature ≥ 38.5℃, frequency of acute cholecystitis ≥3 times, maximum thickness of gallbladder wall ≥ 5 mm, gallbladder neck stone incarceration, diameter of common bile duct ≥8 mm, and surgical experience ≤50 cases were the risk factors for conversion to laparotomy (P < 0.001). A score >3 points was associated with a high risk of conversion to laparotomy. Conclusions The LC scoring system and surgical grading management are reliable and effective tools for predicting and reducing the conversion rate of LC to laparotomy.

Objective: To explore the association between physical activity, anxiety symptoms and academic performance among junior high school students, so as to provide data support for optimizing school physical education and health work and formulating physical activity guidelines. Methods: From September to December 2022, a convenience cluster sampling method was used to survey 2 800 junior high school students in a middle school from Anqing City, Anhui Province. Data were collected on the students anxiety symptoms, academic performance, 24 hour physical activity [moderate to vigorous intensity physical activity(MVPA), light intensity physical activity(LPA), sedentary behavior(SB), and sleep(SLP) duration] as well as demographic characteristics. Compositional data analysis was used to explore the associations between 24 hour physical activity, anxiety symptoms and academic performance among junior high school students, and to predict the optimal time use combination pattern. Results: Among the junior high school students, 16.0% (447 students) reported anxiety symptoms, and 42.0% (1 175 students) achieved excellent or good academic performance. Compositional data analysis showed that increased SLP duration was associated with both reduced anxiety symptoms ( β =-0.18) and decreased academic performance ( β =-0.03) among junior high school students; increased MVPA duration was correlated with fewer anxiety symptoms ( β =-0.02) and lower academic performance ( β =-0.13); in contrast, increased SB duration was linked to more anxiety symptoms ( β =0.09) and higher academic performance ( β =0.09) (all P <0.01). LPA duration exhibited a non linear relationship with anxiety symptoms and academic performance in junior high school students (all P >0.05). The time use combination pattern corresponding to the lowest anxiety symptoms and highest academic performance (top 5%) in adolescents was 611 (520-640) minutes of SLP, 258 (230-320) minutes of SB, 454 (280-610) minutes of LPA, and 117 (20-200) minutes of MVPA per day. Conclusions The 24 hour physical activity of junior high school students is associated with anxiety symptoms and academic performance. Therefore, it is recommended to increase the time spent on SB, MVPA, and LPA for junior high school students, while reducing SB.

Objective:To prepare novel dental composite resins using zinc(Zn)-and nitrogen(N)-modified titanium dioxide(TiO?)nanoparticles(NPs)and mesoporous alumina(Al?O?,r type,20 mm)NPs as reinforcing fillers,systematically evaluating their antibacterial activity,mechanical strength,basic performance,and biosafety to obtain the dental composite resins with excellent antibacterial activity and mechanical strength.Methods:Zn-N-TiO? NPs and mesoporous Al?O? NPs were added into a resin matrix at varying mass ratios to prepare five composite resins:control group(no filler),group 0(Zn-N-TiO?∶Al?O?=1∶0),group 1(Zn-N-TiO?∶Al?O?=1∶1),group 2(Zn-N-TiO?∶Al?O?=1∶2),and group 3(Zn-N-TiO?∶Al?O?=1∶3).Plate colony counting method was used to detect the number of adhered bacteria on composite resin surfaces in various groups and calculate the antibacterial rate;scanning electron microscope(SEM)was used to observe the morphology of adhered bacteria in various groups;universal testing machine was used to measure flexural strength(FS)and elastic modulus(EM)of composite resins in various groups;SEM was used to observe fracture surface morphology of composite resins in various groups;microhardness tester was used to determine Vickers microhardness of the composite resins in various groups;Fourier transform infrared spectroscope was used to detect double bond conversion rate(DC)after 20 s photocuring and calculate curing depth;water contact angle meter was used to measure water contact angle(WCA),water sorption property(WSP),and water solubility level(WSL)of composite resins in various groups;cell counting kit-8(CCK-8)method was used to evaluate relative growth rate(RGR)of the mouse fibroblast L-929 cells cultured in composite resin extracts on days 1,3,and 5 and determine in vitro cytotoxicity grade.Results:The plate colony counting results showed that compared with control group,the colony counts on agar plates in the other groups were significantly reduced,with group 1 showing the lowest count.The SEM images results showed densely distributed and morphologically intact Streptococcus mutans in control group;small clusters of bacteria with depressed cell membranes in group 0 and group 3;sparsely distributed bacteria with obvious membrane shrinkage and cytoplasmic leakage in group 1 and group 2.No statistically significant difference in colony counts was found between group 1 and group 2(P>0.05),but both were lower than the other groups(P<0.05).All the composite resins in experimental groups exhibited>85%antibacterial rates,with group 1 and group 2 exceeding 99%.The composite resins in group 0 showed the lowest FS.With addition of mesoporous Al?O?,the FS of the composite resin in group 1 and group 2 were significantly increased,with the composite resin in group 2 showing the highest FS among all groups.Although the FS of the composite resin in group 3 was lower than that in group 2,but it remained higher than other groups(P<0.05).The SEM images results showed that in control group,the smooth-surfaced sillicon dioxide(SiO?)particles exhibited clear fracture interfaces with resin matrix,with>50%particle exposure;the composite resin in group 0 showed similar morphology and large Zn-N-TiO? agglomerates with tight filler-matrix bonding;the composite resin in group 1,2,and 3 showed resin adhesion to SiO? surfaces(<50%particle exposure)and uneven fracture surfaces.Fractured SiO? spheres were observed in group 2.Filler distribution was uniform in group 1 and group 2,while the minor NP agglomeration occurred in group 3.The composite resin in control group showed the lowest EM.The EM was significantly improved in experimental groups,with group 3 having the highest value.Group 0 exhibited the lowest Vickers microhardness,showing statistically significant differences among other groups(P<0.05).The Vickers microhardness of the composite resion was gradually increased with the rising of Al?O? content.The resins in group 2 and group 3 achieved>45 HV hardness,representing increases of 29.73%and 33.82%compared with control group,and 51.34%and 56.28%compared with group 0.No significant differences in DC of the composite resin were found among groups(P>0.05).The depth of cure for all composite resin groups exceeded 4 mm,with no significance differences observed between various groups(P>0.05).The composite resin in group 0 showed the smallest WCA.The hydrophobicity of the composite resion was increased with the rising of Al?O? content,but all the WCA values remained<80°.The composite resin in group 3 had the largest WCA without statistical significance compared with group 2(P>0.05).Filler incorporation reduced the water sorption/solubility.The composite resin in the CCK-8 assay results showed the composite resins in all groups had RGR>75%,meeting in vitro safety standards.Conclusion:Reinforcing fillers impart superior antibacterial activity and mechanical properties to composite resins.Under experimental conditions,group 2 composite resin achieves optimal comprehensive performance in antibacterial efficacy and mechanical strength,demonstrating promising clinical application potential.

Objective:To establish a rapid quantitative PCR (qPCR) technique for Mycobacterium marinum skin infections, and to analyze its clinical diagnostic efficiency. Methods:DNA was extracted from Mycobacterium marinum colonies and serially diluted (10 -1 to 10 -8). Twelve pairs of previously reported primers and probes, as well as 6 pairs of newly designed primers and probes in this study, were used for qPCR amplification to identify the most sensitive primers and probes for the detection of Mycobacterium marinum. Skin lesion tissues were collected from 72 patients with confirmed Mycobacterium marinum infections (experimental group) and 68 with other mycobacterial infections (control group) at Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences in 2021. These skin tissues were subjected to qPCR amplification, interferon-gamma release assay (IGRA), acid-fast staining, and tissue culture to evaluate the diagnostic efficacy. Results:The newly designed primers and probes targeting the mycobacterial enhanced infection locus 2 (Mel2) demonstrated the highest sensitivity, with a detection limit of 0.86 copies/μl (cycle threshold value = 37) ; the qPCR amplification with the Mel2 primers/probes did not yield positive results when used for the detection of other mycobacteria (including Mycobacterium leprae and Staphylococcus spp) . Among the 72 patients in the experimental group, 44 were positive for qPCR with a sensitivity of 61.1% (95% CI: 49.6% - 71.5%), and 47 were positive for culture with a sensitivity of 65.2% (95% CI: 53.8% - 75.3%) ; all the 68 controls were negative for both qPCR and culture, with their specificities both being 100%. Among 65 patients subjected to IGRA, 31 were positive with a sensitivity of 47.7% (95% CI: 36.0% - 59.6%), while 16 out of 25 controls were negative for IGRA with a specificity of 64.0% (95% CI: 44.5% - 79.8%). Among 58 patients subjected to acid-fast staining, 37 were positive with a sensitivity of 63.8% (95% CI: 50.9% - 74.9%), and 52 out of 66 controls were negative for acid-fast staining with a specificity of 78.8% (95% CI: 67.5% - 86.9%). The combination of qPCR and culture resulted in a sensitivity of 93% and a specificity of 100% for the detection of Mycobacterium marinum. Conclusion:In this study, a highly sensitive qPCR assay was developed for the detection of Mycobacterium marinum, and its combination with culture could further improve the detection sensitivity.

Objective To explore the causal relationship among 731 types of immune cells and breast cancer.Methods Genome-wide association data for immune cells and breast cancer were used.Mendelian randomization analysis was performed using the inverse variance weighting(IVW)and weighted median(WM)methods,and sensitivity analysis was conducted to assess heterogeneity and pleiotropy.Results A total of 19 immune cell phenotypes were identified to potentially have a causal association with breast cancer,using IVW as the main analysis method(P>0.05)and correcting P values using the false discovery rate method at a significance level of 0.05,excluding reverse causality.Of these,eight and 11 immune phenotypes may increase and decrease the risk of breast cancer,respectively.Conclusion This study explored the causal relationship between immune cells and breast cancer.Results show that certain immune cell phenotypes could serve as predictive markers for the early diagnosis of breast cancer and the development of new immun-otherapeutic strategies.

Immune factors play an important role in recurrent spontaneous abortion(RSA),and immune imbalance affects embryo implantation,growth,and development.There is currently no consensus on the etiology and pathogenesis of RSA caused by immune factors.Based on the theory of latent toxic in TCM and combined with the pathological mechanism of the dynamic changes of immune abnormal substances in the body,this article proposed that latent toxic is the key cause of RSA caused by immune factors.Furthermore,it expounded the pathogenic characteristics of latent toxic:combination of heat and blood stasis hidden in the womb,and latent toxic plays a role in embryo formation under qi deficiency conditions.It is established that latent toxin stagnation in the membrane is the pathogenic mechanism.Moreover,this article revealed the variable pathological changes such as the blockage of the inner membrane system and the outer membrane system.Treatment should be based on the basic methods of tonifying qi and nourishing blood,tonifying kidney to secure the Thoroughfare Vessel,clearing heat and cooling blood,promoting blood circulation and removing blood stasis.This article could provide a theoretical basis for TCM syndrome differentiation and treatment of RSA caused by immune factors.

Objective:To identify factors influencing orthostatic intolerance (OI) in patients during initial ambulation following minimally invasive lung surgery and develop and validate a risk prediction model to assist clinical practitioners in screening high-risk patients.Methods:Totally 1 000 patients who underwent minimally invasive lung surgery at the Department of Thoracic Surgery of Peking University Third Hospital from March 2022 to November 2023 were recruited by convenience sampling. Patients were randomly divided into a modeling group ( n=800) and an internal validation group ( n=200) in an 8∶2 ratio. Univariate analysis and logistic regression were applied to determine risk factors for OI in the modeling group. R software was utilized to construct a nomogram model. The model's predictive performance was assessed using the area under the ROC curve ( AUC) for both the modeling and validation groups. Calibration curves were plotted to evaluate consistency, and the Hosmer-Lemeshow test was conducted to confirm model fit. Results:The incidence of OI during initial ambulation was 37.2% (372/1 000). Logistic regression identified BMI, postoperative day 1 drainage volume, postoperative use of nonsteroidal anti-inflammatory drugs (NSAIDs), and initial ambulation pain score as independent risk factors for OI ( P<0.05). The AUC for the nomogram model in the modeling group was 0.645, and 0.694 in the validation group, indicating good predictive accuracy. Calibration curves showed strong agreement between predicted and observed outcomes ( P>0.05) . Conclusions:The constructed risk prediction model demonstrates good predictive ability for OI risk during initial ambulation following minimally invasive lung surgery, which can support clinical identification of high-risk patients. This tool may provide valuable guidance for implementing early, targeted preventive measures.

Objective:To identify factors influencing orthostatic intolerance (OI) in patients during initial ambulation following minimally invasive lung surgery and develop and validate a risk prediction model to assist clinical practitioners in screening high-risk patients.Methods:Totally 1 000 patients who underwent minimally invasive lung surgery at the Department of Thoracic Surgery of Peking University Third Hospital from March 2022 to November 2023 were recruited by convenience sampling. Patients were randomly divided into a modeling group ( n=800) and an internal validation group ( n=200) in an 8∶2 ratio. Univariate analysis and logistic regression were applied to determine risk factors for OI in the modeling group. R software was utilized to construct a nomogram model. The model's predictive performance was assessed using the area under the ROC curve ( AUC) for both the modeling and validation groups. Calibration curves were plotted to evaluate consistency, and the Hosmer-Lemeshow test was conducted to confirm model fit. Results:The incidence of OI during initial ambulation was 37.2% (372/1 000). Logistic regression identified BMI, postoperative day 1 drainage volume, postoperative use of nonsteroidal anti-inflammatory drugs (NSAIDs), and initial ambulation pain score as independent risk factors for OI ( P<0.05). The AUC for the nomogram model in the modeling group was 0.645, and 0.694 in the validation group, indicating good predictive accuracy. Calibration curves showed strong agreement between predicted and observed outcomes ( P>0.05) . Conclusions:The constructed risk prediction model demonstrates good predictive ability for OI risk during initial ambulation following minimally invasive lung surgery, which can support clinical identification of high-risk patients. This tool may provide valuable guidance for implementing early, targeted preventive measures.

Neuroendocrine neoplasm (NEN) is a type of heterogeneous tumor that originates from peptidergic neurons and neuroendocrine cells. The presence of over-expressed somatostatin receptors (SSTR) on the surface of NEN tumor cells has led to the administration of radiolabeled somatostatin analogs (SSA) in combination with over-expressed SSTR, which is called peptide receptor radionuclide therapy (PRRT). The 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacceticacid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE)-based α/β radionuclide therapy is one of the representative therapeutic methods of PRRT. This article reviews the progress of research on α/β radionuclide therapy based on DOTATATE and its related combination therapy, drug toxicity and safety, as well as expectation for modalities with clinical value for NEN treatment.