Objective:To investigate the characteristics of pathogen spectrum and the clinical significance of bronchoalveolar lavage fluid(BALF)metagenomic next-generation sequencing(mNGS)in malignant tumor patients with pulmonary infections.Methods:A retrospective analysis was performed for the patients with malignant tumor who were admitted to department of oncology,the Second affiliated hospital of army medical university,from January 2021 to December 2024.All patients developed respiratory symptoms dur-ing treatment and were diagnosed with pulmonary inflammation based on lung imaging findings,and BALF mNGS and sputum cul-ture were used for pathogen detection.A descriptive analysis was used to summarize the clinical data of patients and the distribution of pathogens,which was compared between patients with different cancer types and metastatic statuses.BALF mNGS and sputum cul-ture were compared in terms of diagnostic performance.Results:A total of 127 patients were enrolled,among whom 70.9%had non-small cell lung cancer,15.0%had small cell lung cancer,and 14.1%had other malignancies.The patients with distant metastasis ac-counted for 48.0%.A total of 145 BALF mNGS tests were performed,among which 84 tests(57.9%)yielded positive results for patho-gens,and 13 tests detected polymicrobial infections,accounting for 15.5%(13/84).A total of 121 pathogenic strains were identified,with fungi(41.3%)and Gram-negative bacteria(39.7%)as the main pathogens,and common pathogens for infection included Pneumo-cystis jirovecii(16.5%),Candida albicans(11.6%),Haemophilus influenzae(11.6%),Klebsiella pneumoniae(10.7%),Pseudomonas ae-ruginosa(10.7%),and Staphylococcus aureus(8.3%).There was a significant difference in the distribution of pathogens between the pa-tients with different types of cancer and statuses of distant metastasis,but Pneumocystis jirovecii remained the most common pathogen for opportunistic infection across all subgroups.A total of 70 patients underwent both sputum culture and BALF mNGS,and the posi-tive rate of sputum culture was only 16.0%,which was significantly lower than that of BALF mNGS(χ2=35.52,P<0.001).The concor-dance rate between sputum culture and BALF mNGS was 48.1%.Conclusion:BALF mNGS can accurately reveal the complex patho-gen spectrum in malignant tumor patients with pulmonary infections,especially the high-risk opportunistic pathogens such as Pneumo-cystis jirovecii.For patients with negative results of sputum culture,BALF mNGS can significantly improve the detection rates of patho-gens and polymicrobial infections.

The incidence and mortality rates of lung cancer remain high, making it the leading cause of cancer-related deaths. In women, the predominant histological subtype is lung adenocarcinoma, commonly associated with epidermal growth factor receptor (EGFR) mutations, and EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can significantly improve patient prognosis. Metastasis of primary lung cancer to the endometrium is extremely rare and is often misdiagnosed as a primary reproductive system tumor, and its occurrence indicates poor prognosis. This article reports a case of an advanced lung adenocarcinoma patient with EGFR mutation, who developed abnormal vaginal bleeding after EGFR-TKIs treatment failure, and biopsy confirmed endometrial metastasis. A review of similar cases is also presented.
.
Humans ; Female ; ErbB Receptors/metabolism* ; Endometrial Neoplasms/genetics* ; Lung Neoplasms/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Adenocarcinoma of Lung/drug therapy* ; Treatment Failure ; Middle Aged ; Adenocarcinoma/genetics*

OBJECTIVES: To investigate the effect of hypaphorine (HYP) on Crohn's disease (CD)‑like colitis in mice and its molecular mechanism. METHODS: Thirty male C57BL/6J mice were equally randomized into WT, TNBS, and HYP groups, and in the latter two groups, mouse models of CD-like colitis were established using TNBS with daily gavage of 15 mg/kg HYP or an equivalent volume of saline. The treatment efficacy was evaluated by assessing the disease activity index (DAI), body weight changes, colon length and histopathology. The effect of HYP was also tested in a LPS-stimulated Caco-2 cell model mimicking intestinal inflammation by evaluating inflammatory responses and barrier function of the cells using qRT-PCR and immunofluorescence staining. GO and KEGG analyses were conducted to explore the therapeutic mechanism of HYP, which was validated in both the cell and mouse models using Western blotting. RESULTS: In the mouse models of CD-like colitis, HYP intervention obviously alleviated colitis as shown by significantly reduced body weight loss, colon shortening, DAI and inflammation scores, and expressions of pro-inflammatory factors in the colon tissues. HYP treatment also significantly increased the TEER values, reduced bacterial translocation to the mesenteric lymph nodes, liver, and spleen, lowered serum levels of I-FABP and FITC-dextran, increased the number of colonic tissue cup cells, and upregulated colonic expressions of MUC2 and tight junction proteins (claudin-1 and ZO-1) in the mouse models. In LPS-stimulated Caco-2 cells, HYP treatment significantly inhibited the expressions of pro-inflammatory factors and increased the expressions of tight junction proteins. Western blotting showed that HYP downregulated the expressions of the key proteins in the TLR4/MyD88 signaling pathway in both the in vitro and in vivo models. CONCLUSIONS HYP alleviates CD-like colitis in mice possibly by suppressing intestinal epithelial inflammation and improving gut barrier function.
Animals ; Male ; Mice, Inbred C57BL ; Crohn Disease/drug therapy* ; Mice ; Humans ; Caco-2 Cells ; Intestinal Mucosa/metabolism* ; Colitis/drug therapy* ; Disease Models, Animal ; Inflammation ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Intestinal Barrier Function

Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

Adolescent idiopathic scoliosis(AIS)is a complex three-dimensional deformity involving coronal,sagittal,and axial planes,with a prevalence that should not be overlooked.With advancements in technology and in-depth research,an increasing number of hospitals and physicians are exploring standardized diagnostic and treatment approaches for AIS.Comprehensive and in-depth understanding is required for AIS,including its etiology,screening and diagnosis,classification,assessment and examination,treatment options,exploration of current focus,and evaluation of quality of life.Such understanding ensures that the diagnostic and treatment are scientific,standardized,and timely.Based on the principles of evidence-based medicine,a consensus on the diagnosis and treatment of AIS is reached after multiple discussions among spinal surgery experts,aiming to provide reference and guidance for clinical practice.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To gain a understanding of the occurrence of cognitive impairment among residents in drinking water-borne endemic fluorosis (drinking water-borne fluorosis) areas, and to study its influencing factors.Methods:In March 2023, a cluster sampling method was used to select local residents aged 18 and above from the drinking water-borne fluorosis areas in Jishan County, Shanxi Province as survey subjects. General demographic data were collected through face-to-face surveys, and a random urine sample was collected once to determine urinary fluoride level. Cognitive function was assessed using the mini-mental state examination (MMSE), and the survey subjects were divided into a cognitive impairment group ( < 27 points) and a control group (27 - 30 points) based on the MMSE scores. A multiple logistic regression model and a decision tree model based on chi-squared automatic interaction detector were constructed to analyze the factors affecting cognitive impairment, and the model fitting effect was evaluated using receiver operating characteristic (ROC) curve.Results:A total of 3 301 subjects were included in the survey, including 2 081 females and 1 220 males. There were 1 515 subjects < 60 years old and 1 786 subjects ≥60 years old, with urinary fluoride level [ M ( Q1, Q3)] of 2.92 (1.78, 4.54) mg/L. There were 1 939 cases in the cognitive impairment group and 1 362 cases in the control group, with a detection rate of 58.74% (1 939/3 301) for cognitive impairment; and the differences in gender, age, education level, marital status, annual household income, alcohol consumption, smoking distribution, and urinary fluoride level between the two groups were statistically significant ( P < 0.05). The results of multiple logistic regression analysis showed that female, ≥60 years, and urinary fluoride > 4.54 mg/L were risk factors for cognitive impairment [ OR (95% CI): 1.25 (1.01, 1.54), 2.66 (2.26, 3.14), 1.32 (1.06, 1.65), P < 0.05]. Education level of primary school or above, annual household income≥12 000 yuan, and mild alcohol consumption were protective factors for cognitive impairment [ OR (95% CI): 0.15 (0.09, 0.25), 0.58 (0.48, 0.68), 0.67 (0.51, 0.87), P < 0.05]. The analysis results of the decision tree model showed that age had the greatest impact on the occurrence of cognitive impairment, followed by annual household income, education level, and urinary fluoride. The areas under the ROC curves of the multiple logistic regression and decision tree model were 0.72 and 0.70 ( P < 0.001), respectively, indicating good model fitting performance. Conclusion:The detection rate of cognitive impairment in residents of drinking water-borne fluorosis areas is relatively high, and age, annual household income, education level, and urinary fluoride are all influencing factors for occurrence of cognitive impairment.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To analyze the clinical efficacy of the Schroth therapy in the treatment of adolescent idiopathic scoliosis.Methods:Relevant clinical studies on Schroth therapy for adolescent idiopathic scoliosis were retrieved from CNKI, Wanfang Data, SinoMed, Chinese Medical Journal Full-text Database, PubMed, Embase, Cochrane Library, and Web of Science. The search time was from the establishment of the database to November 2024. Two authors independently conducted the literature search and imported all potentially eligible studies into EndNote X9 to determine whether the studies met the inclusion criteria. If there was any disagreement, the two parties would discuss and solve it or add a third author for judgment. The scoliosis Cobb angle and the Scoliosis Research Society question-naires-22 (SRS-22) or SRS-23 were extracted from the scoliosis after treatment. The Schroth therapy was compared with other conservative treatment methods (functional exercise or no intervention). The modified Jadad scale was used to evaluate the quality of the included randomized controlled trials. When the heterogeneity between groups was small, the fixed-effect model was used for analysis, and when the heterogeneity between groups was large, the random-effect model was used for analysis. Sensitivity analysis was used to evaluate the stability of the meta-analysis results.Results:A total of 189 patients from 8 literatures were included in the meta-analysis, including 2 Chinese literatures and 6 English literatures, all of which were randomized controlled trials, with a modified Jadad score of 4-6 points. The results of meta-analysis showed that the Cobb angle of Schroth therapy in the treatment of adolescent idiopathic scoliosis was smaller than that of functional exercise or no intervention [ WMD=-3.63, 95% CI (-4.76, -2.51), P<0.001]. SRS-22 or SRS-23 was superior to functional exercise or no intervention [ WMD=0.23, 95% CI(0.14, 0.32), P<0.001], and the difference was statistically significant. The results of subgroup analysis showed that the Cobb angle of Schroth treatment was smaller than that of other conservative treatment methods such as functional exercise [ WMD=-3.48, 95% CI(-4.76, -2.20), P<0.001]. Conclusion:Compared with other conservative treatment methods and no intervention, Schroth therapy can effectively improve the Cobb angle and quality of life in the treatment of adolescent idiopathic scoliosis.