Background and purpose:Human epidermal growth factor receptor 2(HER2)is closely associated with drug efficacy and prognosis in urothelial carcinoma(UC).HER2 is a significant biomarker and therapeutic target in various tumors.In recent years,anti-HER2 antibody-drug conjugates have shown significant clinical efficacy in UC patients with HER2 overexpression.Therefore,an in-depth understanding of HER2 expression and its characteristics in Chinese UC patients is crucial to guide treatment decision-making,optimize treatment strategies and achieve personalized therapy.This study aimed to thoroughly investigate correlation of HER2 expression and clinicopathological characteristics in Chinese patients with UC.Methods:This study was a multicenter study that retrospectively included UC patients from urology departments of 8 tertiary hospitals in 5 geographical regions of China(North China,East China,South China,Central China and Northwest)whose tissue samples were collected from January 2023 to March 2024.Inclusion criteria:① age above 18 years;② UC diagnosed by histopathological or cytological examination;③ complete results of HER2 expression detection using immunohistochemistry(IHC)in the primary tumor site were required.Exclusion criteria:① diagnosed patients with tumors in other parts of the body;② physicians evaluated other situations that were not suitable for inclusion in this study.IHC results for HER2 expression and clinicopathological data were collected.HER2 expression was determined according to the criteria outlined in"Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China",with HER2 2+and 3+defined as HER2 overexpression.The HER2 expression and clinicopathological features were analyzed.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical number:2301268-12)and was registered at China Clinical Trial Registry(registration number:ChiCTR2300069746).Results:A total of 1054 patients with UC were included.Most of the tumors were bladder UC(n=807,76.6%).The mean age of patients was(66.8±10.5)years,and the majority were male(78.5%).The HER2 overexpression rate was 58.4%(n=616),with an additional 23%of patients having HER2 1+expression(n=242),and a small proportion exhibiting negative HER2 expression(n=196,18.6%).HER2 expression was significantly associated with various clinical and pathological characteristics such as Eastern Cooperative Oncology Group(ECOG)performance status,history of cardiovascular disease,history of metabolic disorders,smoking,UC disease location,differentiation grade,pathological type,and tumor stage.Conclusion:Retrospective analysis of multi-center data shows that HER2 expression is frequently observed in Chinese UC patients,with an overexpression rate of up to 58.4%.Furthermore,HER2 expression is closely associated with various clinical and pathological features of UC patients.This study underscores the critical importance of accurately assessing HER2 expression in UC patient to guide personalized therapies.

Objective:To discusses the variations of 7Be, 137Cs and 210Pb activity concentrations in the air in Beijing from March 16, 2021 to March 31, 2023, and their correlation with temperature, precipitation, relative humidity, barometric pressure, PM10 (only limited to 137Cs) and other meteorological parameters. Methods:A total of 60 aerosol samples were collected using the HRHA01-SFS1000/A ultra-large flowair sampler in the automatic radiation monitoring station. The activity concentrations of 7Be, 137Cs and 210Pb in the aerosol samples were measured by GMX-60 low background anti-Compton high purity germanium gamma spectrometer. Pearson correlation coefficient was used to show the correlation of the relevant parameters. Results:The seasonal mean values of 7Be activity concentration were spring 4.31 mBq/m 3, summer 3.53 mBq/m 3, autumn 3.09 mBq/m 3 and winter 2.45 mBq/m 3, respectively, ranging from 1.17 to 7.79 mBq/m 3, with the overall mean of (3.36±1.33) mBq/m 3. The activity concentration of 137Cs ranged from 0.39 to 8.49 μBq/m 3, with an average of (0.59±1.47) μBq/m 3. The average activity concentrations of 210Pb were spring 0.53 mBq/m 3, summer 0.44 mBq/m 3, autumn 0.72 mBq/m 3 and winter 0.75 mBq/m 3, respectively, ranging from 0.21 to 1.36 mBq/m 3, with an average of (0.56±0.26) mBq/m 3. The activity concentration of 7Be was correlated with temperature and pressure ( r=0.38, -0.40), the activity concentration of 137Cs was correlated with precipitation ( r=-0.41), and the activity concentration of 210Pb was correlated with temperature and pressure ( r=-0.31, 0.37). The variation of 137Cs activity concentration in the air showed an obvious seasonal pattern, and the peak value generally appears in spring of each year (March to May), which was related to the frequent spring dust in Beijing. The activity concentration of 210Pb in the air was affected by coal combustion heating in winter, and has a peak value during November to March. Conclusions:The activity concentrations of 7Be, 137Cs and 210Pb in the air in Beijing are within the normal range, showing a seasonal trend.

Objective:To investigate the clinical and electrophysiological characteristics of facial onset sensory motor neuronopathy (FOSMN) syndrome.Methods:Ten patients diagnosed with FOSMN syndrome in Peking Union Medical College Hospital from January 2012 to December 2022 were included. The clinical and electrophysiological characteristics of patients were analyzed and summarized, and the genetic testing was also performed in these patients.Results:The age of onset was (56.6±6.5) years, and the longest survival duration of disease was 10 years. All patients had numbness around the face and mouth as the first symptom and abnormal blink reflex. A total of 52 sensory nerve conduction nerves were detected, among which 2 median nerves and 2 μlnar nerves showed decreased amplitude of sensory nerve action potential. Needle electromyography showed neurogenic lesions, with both progressive and chronic denervation. Whole exome sequencing identified the heterozygous variant c.272A>C in the exon 4 of the SOD1 gene resulting in the amino acid change p.Asp90Ala in 1 patient. In all patients, the disease progressed relentlessly and eventually led to involvement of respiratory muscle. Conclusion:FOSMN syndrome is characterized by abnormal blink reflex and sometimes abnormal sensory nerve conduction may be shown on electrophysiologic testing.

[Objective]To investigate the relationship between platelet activation and traditional Chinese medicine(TCM)syndrome distribution in patients with diabetic peripheral neuropathy(DPN).[Methods]A total of 188 DPN patients admitted to our hospital from February 2020 to December 2022 were collected.The TCM syndrome type usesd the index cluster analysis to draw the cluster diagram.The correspondence between TCM syndrome type and lesion degree was analyzed by simple correspondence analysis,and shown on the two-dimensional plan.It compared the general clinical data,platelet parameters and platelet activation of different TCM syndrome types,so as to explore the relationship between platelet activation and the distribution of TCM syndrome types.[Results]The syndrome types summarized in different positions of the cluster map were different.Among them,D-point interception could be divided into five syndrome types:Qi deficiency syndrome,Yin deficiency syndrome,Yang deficiency syndrome,stagnation of blood stasis syndrome and phlegm-dampness blocking collaterals syndrome.Among the 188 DPN patients,phlegm-dampness blocking collaterals syndrome was found in 18 cases(9.57％),stagnation of blood stasis syndrome in 53 cases(28.19％),Yang deficiency syndrome in 28 cases(14.89％),Yin deficiency syndrome in 39 cases(20.74％),and Qi deficiency syndrome in 50 cases(26.60％).The grade of DPN lesion was grade Ⅰ in 56 cases(29.79％),grade Ⅱ in 76 cases(40.43％),and grade Ⅲ in 56 cases(29.79％).The syndrome of phlegm-dampness blocking collaterals and stagnation of blood stasis in the middle of the two-dimensional projection map did not deviate to a certain grade of DPN lesion degree;Yang deficiency syndrome inclined to grade Ⅲ,Yin deficiency syndrome to grade Ⅱ,and Qi deficiency syndrome to grade Ⅰ.Compared with Qi deficiency syndrome,platelets(PLT),mean platelet volume(MPV),platelet distribution width(PDW),granular membrane protein-140(GMP-140),platelet activating factor(PAF)and E26 transformation specific-l(ETS-l)in patients with Yin deficiency syndrome and Yang deficiency syndrome were significantly higher(P＜0.05),and PLT,MPV,PDW,GMP-140,PAF and ETS-1 in patients with Yang deficiency syndrome were higher than those of Yin deficiency syndrome(P＜0.05).[Conclusion]DPN can be routinely divided into five basic syndrome types:Qi deficiency,Yin deficiency,Yang deficiency,stagnation of blood stasis and phlegm-dampness blocking collaterals.With the development of DPN,TCM syndromes are transformed from Qi deficiency to Yin deficiency to Yang deficiency,while blood stasis and phlegm-dampness blocking collaterals are accompanied by various stages of DPN patients.In the progress of DPN,platelet activation may be involved in the transformation of TCM syndrome types.

Bacillus spp. are probiotics and can secrete a variety of natural antimicrobiol active substances, of which lipopeptides are an important class. Up to now, about 90 lipopeptides have been identified, and most of them are cyclic lipopeptides. surfactin, iturin, fengycin, bacillomycin and polymyxins are widely studied, and the first three have huge potential for application due to their properties of surfactants and anti-fungal, anti-bacterial, anti-viral, anti-tumor and anti-inflammatory functions. In this paper, the research progress in the structure, function, synthesis regulation, separation, purification and production of surfactin, iturin and fengycin was reviewed. Synthetic biology is a vital means to increase the yield of lipopeptides, and in the future, lipopeptides can be used in crop cultivation, animal farming, food, medicine and petroleum industries as well as environmental protection. Future research should be strengthened on the discovery of new lipopeptides, synthesis of high-activity lipopeptides, economical production of lipopeptides on a large scale and their safety evaluation.
Anti-Bacterial Agents ; Anti-Infective Agents/pharmacology* ; Bacillus ; Bacillus subtilis ; Lipopeptides/pharmacology* ; Peptides, Cyclic/pharmacology*

OBJECTIVE：To study the effects of Mahuang xixin fuzi decoction on Toll-like receptors （TLRs）response and cytochrome C oxidase （Cyt-CO）-mediated apoptosis regulation in mice with influenza disease of kidney-yang deficiency. METHODS：Totally 48 male Balb/c mice were randomly divided into normal group （n＝12）and modeling group （n＝36）. The modeling group was intraperitoneally injected with estradiol benzoate solution （8 mg/kg）and intranasally injected with influenza virus H 1N1（20 μL/mice）to establish the influenza disease compound model of kidney-yang deficiency. After modeling ，the mice were randomly divided into model group ，positive drug group （Oseltamivir phosphate capsules ，0.195 g/kg），Mahuang xixin fuzi decoction group （1.802 g/kg，by crude dru g），with 12 mice in each group. Each group was given relevant medicine intragastrically，normal group and model group were given， corresponding volume of normal saline intragastrically 20 mL/kg，once a day ，for consecutive 6 days. During admi-nistration，body weight and anal temperature of mice were mail：xsy407861520@163.com measured daily ；the percentage of initial body weight was calculated. After last medication ，the organ （spleen，thymus and lung ）indexes were calculated ；the pathological changes of lung tissue were observed. The viral load of influenza A virus H 1N1 in lung tissue was detected （reflected by M gene mRNA expression）；mRNA expressions of TLR3，TLR7，myeloid differentiation factor （MyD88）and Caspase- 3 in cardiac tissue as well as the activity of Cyt-CO and the content of cytochrome C （Cyt-C）were also determined. RESULTS ：Compared with normal group，initial body weight percentage and anal temperature of the model group continued to decrease （P＜0.05）；the spleen and thymus indexes were decreased significantly （P＜0.05），while lung index was increased significantly （P＜0.05）；the lung tissue lesions were serious. Viral load in lung tissue ，mRNA expressions of TLR 3，TLR7，MyD88 and Caspase- 3 in cardiac tissue as well as the content of Cyt-C were increased significantly （P＜0.05 or P＜0.01），while the activity of Cyt-CO in cardiac tissue was significantly decreased （P＜0.01）. Compared with model group ，initial body weight percentage and anal temperature of mice in Mahuang xixin fuzi decoction group showed an increasing trend from the fourth day of administration （P＜0.05 or P＜0.01）. The spleen and thymus indexes were increased significantly （P＜0.05），while the lung index was significantly decreased （P＜0.05）；the pathological injury of lung tissue was significantly improved ；viral load in lung tissue ，mRNA expressions of TLR 3 and Caspase- 3 as well as the content of Cyt-C in cardiac tissue were decreased significantly （P＜0.05 or P＜0.01），while the activity of Cyt-CO was increased significantly in cardiac tissue （P＜0.01）. CONCLUSIONS ：Mahuang xixin fuzi decoction can improve influenza disease of kidney-yang deficiency in mice ，the effect may related to inhibit TLRs response and apoptosis regulation pathway mediated by Cyt-CO.

Objective:To analyze the correlation between 1H-MRS in hippocampus and peripheral blood cytokines and T lymphocyte subsets in patients with temporal lobe epilepsy, and to explore the relationship between immune dysfunction and the degree of neuronal injury. Methods:Fifty patients with temporal lobe epilepsy were selected from Affiliated Hospital of Xuzhou Medical University from October 2020 to July 2021.Clinical data of all patients were collected and they were divided into two groups according to MRI results of epileptic sequence: abnormal hippocampal MRI group ( n=20) and normal hippocampal MRI group ( n=30). Bilateral 1H-MRS scanning of hippocampal and detection of T lymphocyte subsets and cytokines in peripheral blood during interictal period were performed in both groups. The levels of hippocampal metabolites NAA, NAA/(Cr+ Cho), T lymphocyte subsets and cytokines in peripheral blood of the two groups were compared.At the same time, the levels of NAA and NAA/ (Cr+ Cho) in the hippocampus on the abnormal side and the normal side in the abnormal hippocampal MRI group were compared within the group. Finally, the correlation between the levels of metabolites NAA, NAA/ (Cr+ Cho) in the hippocampus on the abnormal side obtained by 1H-MRS scanning and T lymphocyte subsets and cytokines in the abnormal group of MRI was analyzed. The data were statistically analyzed by SPSS 26.0 software. Independent sample t-test or Mann-Whitney U test was used for comparison between the two groups. Paired sample t-test was used for intra group comparison of different sides. Spearman correlation analysis was used to analyze the correlation between each index. Results:The NAA and NAA/(Cr+ Cho) values of the abnormal MRI group(normal side NAA: (1.22±0.37), NAA/(Cr+ Cho): (0.56±0.15). abnormal side NAA: (1.02±0.34), NAA/(Cr+ Cho): (0.48±0.13)) were significantly lower than those of the normal MRI group (NAA: (1.51±0.36), NAA/(Cr+ Cho): (0.73±0.19))(NAA: t=2.705, 4.800, both P<0 05; NAA/(Cr+ Cho): t=3.394, 4.914, both P<0 05). The values of NAA and NAA/(Cr+ Cho) in the abnormal side in the MRI abnormal group were significantly lower than those in the normal side( t=6.467, P<0 05). The levels of IL-1β(11.19(3.56, 20.98)pg/ml), IL-5 (3.12(1.86, 6.41)pg/ml), TNF-α(2.55(1.19, 8.28)pg/ml), CD4+ T lymphocytes((43.13±6.82)%) and Th/Ts((1.96±0.66)) in the hippocampal MRI abnormal group were significantly higher than those in normal MRI group (IL-1β: 3.27(1.63, 6.17)pg/ml, IL-5: 1.15(0.96, 2.96)pg/ml, TNF-α: 1.34(1.02, 2.36)pg/ml, CD4+ T: (38.01±7.21)%, Th/Ts: (1.48±0.53))( Z=-3.041, -2.516, -2.496, all P<0.05; t=2.511, 2.810, both P<0 05). The level of CD8+ T ((23.48±5.33)%) in peripheral blood of abnormal MRI group was significantly lower than that of normal group CD8+ T((27.18±6.08)%)( t=2.210, P<0.05). In the abnormal MRI group, the levels of NAA and NAA/ (Cr+ Cho) in the abnormal hippocampus were negatively correlated with the levels of IL-1β, IL-5 and TNF- α ( r=-0.612--0.463, all P<0.05), and positively correlated with CD8+ T lymphocytes ( r=0.537, 0.478, P<0.05). Conclusion:There is neuronal damage and dysfunction in the abnormal hippocampal region of patients with temporal lobe epilepsy with abnormal hippocampal formation, and the degree of neuronal damage is highly correlated with CD8+ T lymphocytes, IL-5, IL-1β and TNF-α in peripheral blood. The imbalance of interictal lymphocyte subsets and chronic inflammatory response may play an important role in the pathogenesis of epilepsy and neuronal injury .

Objective: To investigate the anatomical features of the safe zone for sacral lateral mass screw placement and find the safe trajectory, so as to provide reference for clinical application. Methods: The three-dimensional computed tomography scan materials of sacrococcygeal vertebrae in 60 patients admitted to the Liaocheng People's Hospital of Shandong Province were analyzed by Mimics software to establish three-dimensional models. There were 33 males and 27 females, aged 25-78 years, with an average age of 45.7 years. After the safe zone was separated from sacral lateral mass model, a maximum cylinder was placed into the safe zone according to its anatomical feature. The cylinder was established as safe trajectory. Anatomical data were measured, including the length and diameter of screw trajectory, the distance between the entry point and the middle jaw, and adjacent upper and lower foramen, as well as the intersection angle between the screw direction and sagittal plane, between the screw direction and the adjacent upper end plate. Results: The restriction factor of screw size on S₁, S₂ lateral mass was transverse diameter, while the restriction factor on S₃, S₄ was the distance between adjacent intervertebral foramen. The maximal length of screw from S₁ to S₄ was 30 mm, 35 mm, 30 mm, 14 mm respectively, while the maximal diameter was 12 mm, 9 mm, 5 mm, 5 mm respectively. The best entry point of S₁ mass screw was lateral to the zygopophysis. The best entry point of S₂-S₄ mass screw was located at the midpoint of a line connecting the lateral edge of adjacent posterior sacral foramen approximately about 2 cm from median sacral crest. The leaning angles of screw was increased successively, and the sagittal plane was slightly inclined. There were significant differences between male and female groups in the leaning angle in S₂ [male: (35.8±1.2)°, female: (37.9±3.7)°] and the distance between entry point and median sacral crest [male: (20.5±1.0)mm, female: (19.1±1.4)mm](P<0.05), while there was no significant difference in other parameters (P>0.05). Conclusions Cylindrical bony channel which is feasible for screw placement can be found in the lateral mass of sacrum. Individualized measurement can provide reference for application of lateral mass screw.

Objective To investigate the predictive value of baseline neutrophil-to-lymphocyte ratio (NLR) in the curative effect and prognosis of breast cancer patients treated with neoadjuvant chemotherapy.Methods The clinical data of 304 breast cancer patients received neoadjuvant chemotherapy in Beijing Cancer Hospital during 2010 were retrospectively analyzed.The correlations of baseline NLR with clinicopathological parameters of breast cancer patients were analyzed by Wilcox or Kruskal-Wallis tests,and the correlation of NLR with pathologic complete response (pCR) after neoadjuvant chemotherapy was analyzed by the binary logistic regression.The effect of clinic pathological parameters on the disease-free survival(DFS) of the patients was evaluated by the univariable and muhivariable Cox regression models.Results The medians of NLR in pCR + patients (n =62) and pCR-patients (n =242) were 1.76 and 1.72,respectively,and there was no significant difference between themn (P ＞ 0.05).Multivariate analysis indicated that the TNM stage (P ＜ 0.05) and pCR (P ＜ 0.05) were the independent risk factors influencing the prognosis of breast cancer patients.There was no significant correlation between NLR and 5-year DFS (HR=0.842,95％CI=0.566-1.255,P＞0.05).Condusion NLR lacks the predictive value in the curative effect and prognosis of breast cancer patients treated with neoadjuvant chemotherapy,while TNM stage and pCR are the independent risk factors influencing the prognosis of breast cancer patients.