To investigate the role and potential mechanisms of oropharyngeal microbiota dysbiosis in the development and progression of post-coronavirus disease 2019 (COVID-19) pulmonary fibrosis (PCPF).

A cross-sectional case-control study was conducted, enrolling recovered patients who had been hospitalized for COVID-19 in Xuanwu Hospital Capital Medical University, from December 2022 to May 2023, and had completed a 2-year follow-up after discharge. According to high-resolution computed tomography findings during follow-up, patients were classified into fibrosis group and non-fibrosis group. The α-diversity of the oropharyngeal microbiota between the two groups were compared by Mann-Whitney U test; β-diversity was assessed by non-metric multidimensional scaling (NMDS) and principal coordinates analysis (PCoA). Differences in taxonomic abundance at the phylum, genus and species levels were analyzed by Benjamini-Hochberg method with false discovery rate (FDR) correction. Spearman’s rank correlation was applied to evaluate the associations between microbial taxa and clinical symptoms as well as exercise capacity.

Total of 83 patients were enrolled, 43 cases in fibrosis group and 40 cases in non-fibrosis group. During the 2-year follow-up, patients in fibrosis group had more respiratory symptoms and anxiety. Patients in fibrosis group showed significantly higher scores than non-fibrosis group in mMRC scale (U=676.0, P=0.008), BCSS score (U=625.0, P=0.029), CAT score (t=2.127, P=0.036), CET score (U=538.5, P=0.002) and Hamilton Anxiety Rating Scale score (U=634.0, P=0.039); The 6-minute walking distance of patients in fibrosis group was shorter (U=598.5, P=0.017), all with significant differences. Microbiome analysis revealed significantly elevated α-diversity of oropharyngeal microbiota in fibrosis group (Chao1 index: U=580.5, P=0.010; Shannon index: U=557.0, P=0.005; Simpson index: U=513.0, P=0.001; Faith’s phylogenetic diversity: U=579.0, P=0.010; Simpson’s evenness index: U=577.0, P=0.010; Heip’s evenness index: U=529.0, P=0.035), with significant differences. β-diversity analysis showed distinct separation of microbial community structure between the two groups. Taxonomic analysis demonstrated that the relative abundances of potential pro-inflammatory taxa, including Prevotella (U=358.0, P<0.001), Veillonella (U=418.0, P<0.001) and Streptococcus (U=538.0, P=0.003), were significantly increased in fibrosis group, whereas Neisseria (U=226.0, P<0.001) was significantly decreased. Correlation analysis indicated that the abundance of Streptococcus parasanguinis was positively associated with mMRC (r=0.24, P=0.04) and CAT (r=0.27, P=0.02). In contrast, Fusobacterium periodonticum abundance was negatively correlated with CAT (r=－0.30, P<0.01) and Warrick score (r=－0.26, P=0.02), but positively correlated with 6MWD (r=0.26, P=0.02). Furthermore, Veillonella rogosae and Streptococcus infantis were both significantly and negatively correlated with Warrick score (r=－0.30, P<0.01; r=－0.28, P=0.01).

Patients with post-COVID-19 pulmonary fibrosis exhibited persistent oropharyngeal microbial dysbiosis, which is closely associated with clinical symptoms and functional impairment. The oropharyngeal microbiome might serve as a potential non-invasive biomarker for risk assessment and a novel therapeutic target for post-COVID-19 pulmonary fibrosis.

To investigate the independent predictive factors for diagnosis of tuberculous meningitis (TBM) based on regional characteristics in Qinghai, China, and to construct and validate a diagnostic prediction model.

The clinical data of 931 patients with infectious meningitis, including 739 cases with TBM and 192 cases with non-tuberculous infectious meningitis (non-TBM) treated at Qinghai Provincial Fourth People’s Hospital from January 2019 to January 2024 were collected, retrospectively. They were divided into a training set (651 cases, including 522 cases of TBM and 129 cases of non-TBM) and a validation set (280 cases, including 217 cases of TBM and 63 cases of non-TBM) with a ratio of 7∶3. The influencing factors of TBM diagnosis were screened by Lasso regression and multivariate Logistic regression, and a nomogram prediction model was constructed. The diagnostic efficiency of five machine learning models (decision tree, Logistic regression, random forest, support vector machine and extreme gradient boosting) were evaluated and compared by the receiver operating characteristic (ROC) curve.

The general demographic data and biochemical parameters between patients in training set and validation set were without significant differences (all P>0.05); the baseline characteristics between patients in TBM group and non-TBM group across both the training set and validation set were also without significant differences (all P>0.05). By Lasso dimensionality reduction screening of predictive variables and multivariate regression analysis, a total of 6 independent predictors for TBM were identified: consciousness disorder (OR=2.988, 95%CI: 1.242-7.555, P=0.017), gamma interferon release assay (IGRA) (OR=4.279, 95%CI: 2.074-9.120, P<0.001), CSF monocyte ratio≥50% (OR=4.061, 95%CI: 1.88-9.174, P<0.001), magnetic resonance imaging (MRI) suggesting tuberculoma (OR=7.080, 95%CI: 2.019-34.77, P=0.006), MRI suggesting cranial base meningeal enhancement (OR=3.022, 95%CI: 1.429-6.519, P=0.004) and computerized tomography (CT) showing pulmonary lesions (blood disseminated tuberculosis: OR=46.140, 95%CI: 8.765-856.9, P<0.001). AUC of the Logistic regression model in training set and validation set were both 0.948 (95%CI: 0.927-0.969, 0.920-0.975), with sensitivities of 87.16% and 85.71%, and specificities of 89.92% and 90.48%. The Extreme Gradient Boosting (XGB) model performed the best in diagnosing TBM (AUC=0.954).

The Logistic regression model based on clinical and imaging features exhibits excellent diagnostic accuracy for TBM and is suitable for clinical application.

To investigate the expression profile of novel immunomodulatory factor interleukin (IL)-41 in pediatric patients with Mycoplasma pneumoniae pneumonia (MPP), and to analyze its correlation with disease severity, diagnostic efficacy and value for predicting severe progression.

Total of 32 children with MPP under 18 years old, admitted to Beijing Friendship Hospital, Capital Medical University and Hebei Yiling Hospital throughout 2024 were enrolled for retrospective cohort study, including 17 cases of mild disease (mild group) and 15 cases of severe disease (severe group), while 8 healthy children undergoing physical examinations were selected as the control group. Serum IL-41 level was detected in enrolled children by enzyme-linked immunosorbent assay (ELISA), and parameters such as gender, age, C-reactive protein (CRP), procalcitoninand (PCT) and IL-6 levels were compared, respectively. The diagnostic efficacy of these markers for severe MPP was evaluated by receiver operating characteristic (ROC) curve, the relationships between serum IL-41 level and clinical indicators were analyzed by correlation heatmaps.

Among the 32 enrolled ediatric patients with MPP, there were 11 males (34.4%) and 21 females (65.6%), with a mean age of (8.60±2.89) years old. There was no statistically significant difference in age between mild group and severe group [(9.06±3.45) years old vs. (8.07±2.09) years old] (t=0.393, P=0.697). IL-41 level of MPP children in mild group was significantly higher than that of healthy control group [(182.191±65.364) pg/ml vs. (137.628±2.914) pg/ml], with significant difference (t=2.805, P=0.013). But there were no significant difference of IL-41 level between severe group and healthy control group, or between mild group and severe group (all P>0.05). The area under the ROC curve (AUC) for diagnostic differentiation between mild group and severe group by individual biomarkers IL-41, CRP and IL-6 were 0.652, 0.590 and 0.522, respectively, all showing suboptimal performance. However, the three idicators combined AUC significantly improved to 0.768 (95%CI: 0.598-0.938, P=0.013), with the sensitivity and specificity of 93.8% and 57.1%, respectively. In mild group, the IL-41/CRP ratio [24.47 (7.4, 41.1)] and IL-41/IL-6 ratio [26.88 (9.1, 34.6)] were significantly higher than those of severe group [10.81 (1.3, 18.9) and 9.85 (1.7, 15.1)], with significant differences (Z=－3.946 and －1.957, both P<0.001). Spearman correlation analysis demonstrated a significant positive correlation between serum IL-41 and IL-6 levels of patients with MPP (r=0.64, P=0.020).

Serum IL-41 level is significantly elevated in children with mild MPP, which was elevated but without significance in severe MPP cases, suggesting that IL-41 may exert a protective effect against severe disease as an anti-inflammatory factor. Combined detection of IL-41, CRP and IL-6 enhances the diagnostic accuracy for severe MPP, and dynamic monitoring of IL-41 level may aid in disease progression assessment of patients with MPP.

To investigate the correlation between the expression levels of CXC chemokine receptor 3 (CXCR3), the ligands (CXCL10, CXCL11) and the clinical characteristics and disease severity of patients with tuberculosis.

Clinical data from 81 tuberculosis patients treated in Hebei Chest Hospital between December 2022 and October 2023 were collected and baseline characteristics among tuberculosis patients with different disease severities were compared; the correlation between the positive expression rates of chemokine CXCR3, CXCL10 and CXCL11 and tuberculosis lesion severity were analyzed by a generalized mixed-effects model; the associations between immune microenvironment indicators and the positive expression rates of chemokine CXCR3, CXCL10 and CXCL11 were analyzed by Pearson correlation analysis; the predictive accuracy of the positive expression rates of chemokine CXCR3, CXCL10 and CXCL11 for tuberculosis lesion severity were evaluated; the predictive performance of these chemokine expression rates were assessed by DeLong test and receiver operating characteristic (ROC) curves.

Among the 81 pulmonary tuberculosis patients, 52 cases were male and 29 cases were female, with a mean age of (42.95±6.83) years old. Tuberculosis patients with a history of smoking, no BCG vaccination and poor ventilation showed significantly higher positive expression rates of CXCR3, CXCL10 and CXCL11 (all P<0.05). The tuberculosis patients with B cells<16%, CD4⁺ T lymphocytes<30%, CD8⁺ T lymphocytes<31%, natural killer (NK) cells<15% and macrophages≥66% showed significantly elevated positive expression rates of CXCR3, CXCL10 and CXCL11 (all P<0.05). Hierarchical regression analysis showed that smoking history had a significantly positive impact on the positive expression rates of CXCR3 (t=1.574, P=0.002), CXCL10 (t=1.638, P=0.015) and CXCL11 (t=3.175, P=0.025) of patients with pulmonary tuberculosis. BCG vaccination history and poor ventilation had significantly negative effects on the positive expression rates of CXCR3, CXCL10 and CXCL11, with significant differences (BCG vaccination history: t=－0.809, P=0.008; t=－1.975, P=0.019; t=－4.546, P=0.022; poor ventilation: t=－1.503, P=0.015; t=－1.335, P=0.007; t=－2.324, P=0.008). As the severity of pulmonary tuberculosis progressed, smoking history (χ²=31.867, P<0.001), ventilation condition (χ²=15.178, P=0.001), macrophage ratio (F=9.921, P<0.001), CXCR3 positivity (χ²=18.277, P<0.001), CXCL10 positivity (χ²=15.178, P=0.001) and CXCL11 positivity (χ²=19.708, P<0.001) increased gradually among patients with pulmonary tuberculosis. BCG vaccination history (χ²=15.178, P=0.001), B cells (F=10.947, P<0.001), CD4⁺ T lymphocytes (F=11.471, P<0.001), CD8⁺ T lymphocytes (F=10.911, P<0.001) and NK cells (F=11.124, P<0.001) levels decreased gradually, with significant differences. The results of the generalized linear mixed-effects model analysis showed that compared with patients who were negative for CXCR3, CXCL10 and CXCL11, the risk of mild lesion severity of patients with positive CXCR3, positive CXCL10 and positive CXCL11 in pulmonary tuberculosis were 2.125, 2.080 and 2.153, respectively; OR for moderate lesion severity were 2.723, 3.294 and 1.934, respectively; and OR for severe lesion severity were 2.832, 2.501 and 2.271, respectively. Pearson correlation analysis results showed that B cells, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes and NK cells were significantly and negatively correlated with the positive expression rates of CXCR3, CXCL10 and CXCL11 (all P<0.001), while macrophages were significantly and positively correlated with the positive expression rates of CXCR3, CXCL10 and CXCL11 (r=0.463, 0.489, 0.677, all P<0.001). The prediction of three combined indicators for the severity of pulmonary tuberculosis lesions (moderate-severe and severe) had a significantly higher accuracy rate than any single indicator alone (all P<0.05). The results of ROC curve analysis showed that the optimal cut-off values for combined prediction on the severity of pulmonary tuberculosis lesions as moderate-severe or severe were 82.75% and 95.71%, respectively. DeLong test indicated that the combined prediction of three factors had a higher efficacy (AUC) than individual factor (all P<0.05).

The positive expression rates of CXCR3, CXCL10 and CXCL11 are closely related to the clinical characteristics and lesion severity of patients with pulmonary tuberculosis, which may be involved in local immune regulation of pulmonary tuberculosis.

To investigate the effect of acupoint application of Xiaoluosan on cytokines and T lymphocyte subsets in children with Mycoplasma pneumoniae pneumonia (MPP).

Clinical data of 102 children with MPP in the Department of Pediatrics, Taihe Traditional Chinese Medicine Hospital affiliated to Anhui University of Traditional Chinese Medicine from October 2023 to October 2024 were collected. Total of 102 random numbers were generated and sorted either in ascending order or according to an odd-even criterion; odd-numbered numbers were assigned to the experimental group (51 cases) and even-numbered numbers to control group (51 cases). Children in control group received treatment with azithromycin, while those in experimental group additionally received Xialuosan patch application. Clinical efficacy, improvement of signs and symptoms, lung function indicators, serum cytokine levels, distribution of T lymphocyte subsets and incidence of adverse reactions of MPP cases between experimental group and control group were compared by Mann-Whitney U test or Pearson χ² test.

Compared with baseline levels before treatment, the forced vital capacity (FVC), peak flow velocity (PEF) and the ratio of forced expiratory volume to forced vital capacity in one second (FEV1/FVC) increased significantly in both groups; but the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) reduced significantly, all with significant differences (all P<0.05). The clinical total effective rate (98.04%, 50/51), FVC (2.70±0.43) L, PEF (6.54±0.82) L/s and FEV1/FVC (76.59±6.88) of cases in experimental group were significantly higher than those of control group [clinical total effective rate: 76.47%, 39/51, FVC: (2.18±0.31) L, PEF: (5.27±0.70), FEV1/FVC: (70.92±6.14)] (χ²=10.667, t=7.005, t=8.412, t=4.391; all P<0.001). The recovery time of routine blood test indices (t=7.223, P<0.001), disappearance time of cough (t=6.631, P<0.001), disappearance time of wheezing and dyspnea (t=4.856, P<0.001), disappearance time of pulmonary rales (t=8.788, P<0.001) and defervescence time (t=12.097, P<0.001) were all significantly shortened in the experimental group. Serum levels of IL-6 [(6.44±0.78) pg/ml vs. (9.55±1.21) pg/ml: t=15.428, P<0.001], TNF-α [(8.24±0.93) pg/ml vs. (10.93±1.32) pg/ml: t=11.897, P<0.001] and CRP [(1.21±0.21) mg/L vs. (2.09±0.34) mg/L: t=15.726, P<0.001] of cases in experimental group were significantly lower than those of control group, all with significant differences. After treatment, the levels of CD3⁺ T and CD4⁺ T lymphocytes of children in both groups were significantly higher than those of pre-treatment levels, while the level of CD8⁺ T lymphocytes was significantly decreased (all P<0.05). After treatment, the levels of CD3⁺ T lymphocytes [(71.02±7.83)%] and CD4⁺ T lymphocytes [(43.28±5.24)%] of cases in experimental group were significantly higher than those of control group [(67.55±6.42)% and (38.99±4.65)%], whereas the CD8⁺ T lymphocyte level [(18.24±1.34)% vs. (21.11±1.99)%] was significantly lower than that of control group (t=2.447, 4.373, 8.543; all P<0.001), with significant differences. The incidence of adverse reactions was 7.84% of cases in control group and 1.96% in experimental group, but without significant difference (χ²=1.950, P=0.161).

Xiaoluosan acupoint application to MPP children can effectively reduce the levels of IL-6, TNF-α and CRP, inhibit inflammatory response, regulate T lymphocyte subsets and enhance the clinical efficacy.

To investigate the clinical characteristics of anti-tuberculosis drug-induced liver injury (AT-DILI) and identify the influencing factors of nonrecovery outcomes, so as to provide evidence for risk identification and follow-up the management during anti-tuberculosis therapy.

Clinical data of 136 patients with AT-DILI admitted to the Fourth People’s Hospital of Qinghai Province from January 2020 to May 2024 were collected, retrospectively, including demographic characteristics, underlying liver disease, time to liver injury onset, clinical pattern of AT-DILI, severity grade, laboratory indicators, treatment and outcomes. Patients were divided into improved group (112 cases) and unresolved group (24 cases) according to the clinical outcomes, and clinical characteristics were compared between the two groups by a unified set of variables. The influencing factors for unrecovery outcomes in patients with AT-DILI were analyzed by Univariate and multivariate Logistic regression analyses. Receiver operating characteristic (ROC) curves were established based on the predicted probabilities from the final Logistic regression model, which contained hepatitis B and gamma-glutamyl transferase (GGT) level, and to evaluate the discriminative performance of this model for nonrecovery outcomes in patients with AT-DILI.

Among the 136 patients, 86 (63.2%) were male and 50 (36.8%) were female; 69 (50.7%) patients were complicated with hepatitis B, and 18 (13.2%) patients received artificial liver support therapy. Overall, 112 patients (82.4%) recovered or improved, whereas 24 (17.6%) patients had nonrecovery outcomes. AT-DILI mainly occurred during 60 days after initiation of anti-tuberculosis therapy (118 cases, 86.8%). Cholestatic pattern was the most common (96 cases, 70.6%), and grade 4 liver injury was the most common severity grade (49 cases, 36.0%). Age distribution, whether complicated with hepatitis B, severity of liver injury, drug resistance status, GGT, serum sodium (Na), procalcitonin (PCT) and hemoglobin (Hb) between the improved group and unresolved group of patients with AT-DILI were significantly different (all P<0.05). Multivariate Logistic regression analysis showed that hepatitis B (OR=7.838, 95%CI: 2.039-30.130, P=0.003) and GGT level (OR=1.012, 95%CI: 1.001-1.024, P=0.046) were both influencing factors of unresolved outcomes for patients with AT-DILI. The combined model based on hepatitis B and GGT level showed certain discriminative performance for nonrecovery (AUC=0.886, 95%CI: 0.819-0.953, P<0.001).

AT-DILI often occurs in early stage of anti-tuberculosis treatment, so liver function monitoring within the first two months after medication administration should be emphasized. Concomitant hepatitis B and elevated GGT level are risk factors for unresolved outcomes in patients with AT-DILI, which can serve as reference indicators for early identification of high-risk patients and the follow-up management.

To investigate the clinical characteristics of pediatric patients with pertussis across different age groups.

Clinical data of 567 pediatric patients with pertussis diagnosed at Chengdu Public Health Clinical Medical Center from January 2022 to December 2024 were analyzed, retrospectively. Patients were grouped into≤3 months group (118 cases), 3-36 months group (180 cases), 36 months-6 years old group (115 cases) and>6 years old group (154 cases). General information, vaccination history, epidemiological characteristics, clinical manifestations, and laboratory test results [white blood cell (WBC) count, absolute lymphocyte count (ALC) and platelet (PLT) count] were collected, respectively. Intergroup comparisons were performed by Chi-square test or Kruskal-Wallis H test.

Among the 567 enrolled children, the incidence rates were higher in 36 month-6 years old [20.3% (115/567)] and>6 years old groups [27.2% (154/567)] , respectively; Cases occurred throughout the year, with a peak incidence in summer (61.2%, 347/567), followed by spring (22.4%, 127/567); while 262 children (46.2%) were unvaccinated or not fully immunized. The main clinical symptoms included paroxysmal spasmodic cough (84.7%, 480/567), vomiting (35.8%, 203/567) and crowing-like stridor (29.6%, 168/567). The incidence of paroxysmal spasmodic cough (χ²=38.36, P<0.001), crowing stridor (χ²=47.44, P<0.001), wet rales or wheezing (χ²=92.22, P<0.001) and pneumonia (χ²=47.49, P<0.001) were significantly different among children with pertussis of all age groups; moreover, the incidence decreases with age increasing in pediatric patients, both≤3 month old group and 3-36 month old group exhibiting significantly higher rates of these clinical manifestations compared with>6 years old group (all P<0.001). White blood cell (WBC) count (H=68.65, P<0.001), absolute lymphocyte count (ALC) (H=163.25, P<0.001) and platelet (PLT) count (H=190.72, P<0.001) were significantly different among children with pertussis of all age groups; the above mentioned indicators were significantly higher in≤3 month old group and 3-36 month-old group compared with 36 month to 6 years old group and>6 years old group, all with significant differences (all P<0.001).

Clinical manifestations of pertussis in young children are typical, particularly evident in infants aged≤3 months. WBC, ALC and PLT levels are generally elevated in young pediatric patients, which provides valuable reference for early diagnosis of pertussis when combined with clinical presentations.

To explore the application effect of comprehensive intervention measures combined with photodynamic therapy on children with condyloma acuminatum (CA).

Clinical data of 30 children with CA who received aminolaevulinic acid-photodynamic therapy (ALA-PDT) at the Department of Dermatology and Venereology, Beijing Ditan Hospital, Capital Medical University from January 2018 to December 2024 were analyzed, retrospectively. Based on conventional PDT, a series of comprehensive intervention measures such as targeted psychological intervention, full-process pain management, postoperative wound skin management, and health knowledge education were implemented for CA children and their families. After the treatment was completed, regular follow-up were conducted for 6 months to collect statistics on the treatment efficacy, treatment compliance, and related adverse reactions of the children.

Among the 30 children with CA, 18 cases were boys and 12 cases were girls, aged from 2 to 14 years old [(6.3±2.4) years old], the disease duration was 1 to 6 months [(4.2±1.2) months], the diameter of the lesions was 0.2 to 1.8 cm [(1.22±0.10) cm], and the number of lesions was 1 to 8 [(4.43±0.8)]; 20 cases (66.67%) had lesions involving the external genitalia, 8 cases (26.67%) involved the perianal, and 2 cases (6.66%) had external genitalia and perianal lesions. After PDT combined with comprehensive interventions, 22 cases (73.33%) were cured, 7 cases (23.33%) were markedly effective, and 1 case (3.33%) was ineffective. The total treatment effective rate was 96.67% (29/30). No case recurred during the follow-up for 6 months. All children completed the full course of treatment, and 25 cases (83.33%) were fully compliant, 5 cases (16.67%) were partially compliant. No serious systemic adverse reactions occurred during the treatment, and local adverse reactions were all mild to moderate, and may occur concomitantly on the same child. A total of 11 children (36.67%) had at least one local adverse reaction, 6 cases (20.00%) had pain, 6 cases (20.00%) had local erythema, 2 cases had blister erosion (6.67%), 1 case had itching with burning sensation (3.33%), and 3 cases had pigmentation (10.00%); All adverse reactions were completely relieved after local symptomatic treatment and did not affect the ALA-PDT treatment process.

After the comprehensive intervention measures combined with ALA-PDT, CA children showed good treatment compliance, and the adverse reactions can be effectively alleviated.