OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

In the clinical stage, suspected hemolytic plasma may cause hemolysis illness, manifesting as symptoms such as heart failure, severe anemia, etc. Applying a deep learning method to plasma images significantly improves recognition accuracy, so that this paper proposes a plasma quality detection model based on improved "You Only Look Once" 5th version (YOLOv5). Then the model presented in this paper and the evaluation system ‌were introduced‌ into the plasma datasets, and ‌the average accuracy of the final classification reached 98.7%‌. The results of this paper's experiment were obtained through the combination of several key algorithm modules including‌ omni-dimensional dynamic convolution, pooling with separable kernel attention, residual bi-fusion feature pyramid network, ‌and‌ re-parameterization convolution. The method of this paper‌ obtains the feature information of spatial mapping efficiently, and enhances the average recognition accuracy of plasma quality detection. This paper presents a high-efficiency detection method for plasma images, aiming to provide a practical approach to prevent hemolysis illnesses caused by external factors.
Algorithms ; Humans ; Hemolysis ; Plasma ; Deep Learning ; Image Processing, Computer-Assisted/methods*

Objective:To analyze the genetic characteristics and evolutionary origin of hepatitis B virus (HBV) subgenotype D3 in China in 2020.Methods:Serum samples and demographic details from patients infected with HBV D3 subgenotype were collected. HBV genomic sequences were obtained by nested PCR amplification and subsequent sequencing. Phylogenetic analysis, nucleotide homology, amino acid mutation and evolution rate of the S protein were conducted by comparing with reference sequence using bioinformatics tools.Results:The complete HBV gene sequences of 14 samples of D3 subtype HBV were obtained. Compared with 97 reference sequences, it was found that the sequences with the highest homology were from India, Mongolia, Iran and China, with the homology ranging from 96.0% to 97.9%. Mutations of 24 amino acids were found in 14 strains of D3 subtype. Among them, T131A, Y134F and T140I were associated with immune escape-related mutations. The genetic diversity of HBV D3 subtype increased slowly before 1975, remained relatively constant from 1975 to 2000, and began to decline after 2000. Evolutionary rate analysis showed that samples QGLD D3-02 and 03 originated from a common ancestor with the Iranian reference strain in 1872, and the other 12 samples QGLD D3-04-17 originated from a common ancestor with the Mongolian reference strain in 1843.Conclusions:The gene sequence of HBV D3 subtype in China had the highest homology with reference sequences from India, Iran, Mongolia and China. Evolutionary rate analysis revealed that 14 cases of HBV D3 subtype originated from a common ancestor with reference strains from Mongolia and Iran, which enriched the sequence and evolution information of HBV D3 subtype and provided a reference basis for the molecular epidemiological study of HBV.

Objective:To evaluate the mediating effect of electrocardiographic (ECG) indicators in the association between short-term exposure to fine particulate matter (PM 2.5) and blood pressure and to explore the key PM 2.5 element constituents that produce the mediating effect. Methods:Based on a cross-sectional survey across 10 cities in the Beijing-Tianjin-Hebei region and surrounding areas, PM 2.5 and its element constituents were collected from the nearest air monitoring superstation. Blood pressure and ECG indicators of participants were obtained through physical examinations. A multivariate linear regression was used to evaluate the effect of short-term exposures to PM 2.5 on blood pressure. A mediation analysis was used to identify the mediating effect of ECG indicators in the association between exposure to PM 2.5 and its element constituents and blood pressure. Results:The age of the 1 793 participants was (65.1±13.3) years, and 885 (49.4%) were males. During the study period, the daily mean concentration of PM 2.5 was (70±45) μg/m 3, and the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) were (139±20), (82±11), (101±13), and (57±17) mmHg (1 mmHg=0.133 kPa), respectively. The results of the multivariate linear regression showed that for every 10 μg/m 3 increase in PM 2.5 on the same day (lag 0), DBP increased by 0.15 (95% CI: 0.02-0.28) mmHg, and PP decreased 0.18 (95% CI: 0.36-0.01) mmHg. The exposure to 14 elemental constituents, such as Ga, Co and Se, was associated with an increase in DBP, while the exposure to 17 elemental constituents, such as Cs, Se and Ag, was associated with a decrease in PP. At lag 0, the PM 2.5-induced increase in DBP was mediated by the QRS interval (mediation percentage of 18.98%), and the PM 2.5-induced decrease in PP was mediated by the QT interval (mediation percentage of -6.31%). The exposure to K, Br, Pb, Zn, Ca, Co, Pd, Cu, and As constituents was associated with increases in DBP mediated by prolonged QRS interval. The exposure to Pb, Zn, K, and As constituents was associated with decreases in PP mediated by prolonged QRS interval. Conclusion:ECG indicators such as QRS interval may mediate the association between short-term exposure to PM 2.5 and its element constituents and blood pressure.

Objective To analyze the law of acupoint selection and compatibility of acupuncture and moxibustion and the application law of acupuncture and moxibustion in the treatment of lactational mastitis using complex network technology.Methods The clinical research literature about acupuncture and moxibustion treatment of lactational mastitis was retrieved from CNKI,CBM,Wanfang Data,VIP and PubMed from the establishment of the databases to March 15,2025.The literature was screened according to the standards to build a prescription database of acupuncture and moxibustion treatment of lactational mastitis.SPSS Modeler 18.0 software was used to analyze association rules,and Gephi 0.9 software was used for complex network analysis.Results A total of 108 articles were included.141 acupuncture and moxibustion prescriptions were extracted,involving 74 acupoints,with a total use frequency of 677 times.The high-frequency acupoints were Jianjing,Danzhong,Rugen,Zusanli,Neiguan,etc.Specific acupoints were mainly composed of Wushu acupoints(169 times,21.10%);the acupoints were mainly distributed in the limbs(36);the most frequently used meridian was stomach meridian(168 times,24.82%).The combination of acupoints with the highest correlation was Jianjing-Neiguan-Rugen.Complex network analysis identified 22 core acupoints,with the most commonly used acupuncture method being filiform needle acupuncture(79 times).Conclusion Acupuncture and moxibustion treatment of lactational mastitis pays special attention to the selection of stomach meridian.The compatibility mode is mainly from top to bottom,and the corresponding acupoints are selected according to syndrome differentiation.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

ObjectiveTo investigate the mechanism by which 2，3，5，4'-tetrahydroxyldiphenylethylene-2-O-glucoside （THSG） mitigates cerebral ischemia/reperfusion （CI/R） injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham， model， SAS （40 mg·kg^-1）， and low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） THSG groups， with 10 rats in each group. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring， and cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 （CCK-8） assay， and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 （PINK1） and leucine zipper/EF-hand-containing transmembrane protein 1 （LETM1） in neurons. Transmission electron microscopy （TEM） was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 （TOMM20）， autophagy-associated protein p62， microtubule-associated protein light chain 3 （LC3）， cysteinyl aspartate-specific proteinase-9 （Caspase-9）， B-cell lymphoma 2-associated protein X （Bax）， and cytochrome C （Cyt C）. ResultsCompared with the sham group， the model group exhibited increased infarct volume （P<0.01） and neurological deficit scores （P<0.01）， neuronal structure was disrupted with reduced Nissl bodies. （P<0.01）， mitochondrial swelling/fragmentation， decreased PINK1/LETM1 co-localization （P<0.01）， upregulated protein levels of LC3Ⅱ/LC3Ⅰ， TOMM20， Caspase-9， Bax， and Cyt C （P<0.01）， downregulated protein level of p62 （P<0.05）， weakened PC12 viability （P<0.01）， and elevated mitochondrial calcium level （P<0.01）. Compared with the model group， THSG and SAS groups showed reduced infarct volumes （P<0.05，P<0.01） and neurological deficit scores （P<0.05，P<0.01）， mitigated mitochondrial damage， and increased PINK1/LETM1 co-localization （P<0.01）. Medium/high-dose THSG and SAS alleviated the neurological damage， increased Nissl bodies （P<0.05，P<0.01）， downregulated the protein levels of p62， TOMM20， Caspase-9， Bax， and Cyt C （P<0.05，P<0.01）， and elevated the LC3Ⅱ/LC3Ⅰ level （P<0.05，P<0.01）. High-dose THSG enhanced PC12 cell viability （P<0.01）， increased PINK1/LETM1 co-localization （P<0.01）， and reduced mitochondrial calcium （P<0.01）. ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway， reducing the mitochondrial calcium overload， and promoting mitophagy.

ObjectiveTo investigate the mechanism by which 2，3，5，4'-tetrahydroxyldiphenylethylene-2-O-glucoside （THSG） mitigates cerebral ischemia/reperfusion （CI/R） injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham， model， SAS （40 mg·kg^-1）， and low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） THSG groups， with 10 rats in each group. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring， and cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 （CCK-8） assay， and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 （PINK1） and leucine zipper/EF-hand-containing transmembrane protein 1 （LETM1） in neurons. Transmission electron microscopy （TEM） was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 （TOMM20）， autophagy-associated protein p62， microtubule-associated protein light chain 3 （LC3）， cysteinyl aspartate-specific proteinase-9 （Caspase-9）， B-cell lymphoma 2-associated protein X （Bax）， and cytochrome C （Cyt C）. ResultsCompared with the sham group， the model group exhibited increased infarct volume （P<0.01） and neurological deficit scores （P<0.01）， neuronal structure was disrupted with reduced Nissl bodies. （P<0.01）， mitochondrial swelling/fragmentation， decreased PINK1/LETM1 co-localization （P<0.01）， upregulated protein levels of LC3Ⅱ/LC3Ⅰ， TOMM20， Caspase-9， Bax， and Cyt C （P<0.01）， downregulated protein level of p62 （P<0.05）， weakened PC12 viability （P<0.01）， and elevated mitochondrial calcium level （P<0.01）. Compared with the model group， THSG and SAS groups showed reduced infarct volumes （P<0.05，P<0.01） and neurological deficit scores （P<0.05，P<0.01）， mitigated mitochondrial damage， and increased PINK1/LETM1 co-localization （P<0.01）. Medium/high-dose THSG and SAS alleviated the neurological damage， increased Nissl bodies （P<0.05，P<0.01）， downregulated the protein levels of p62， TOMM20， Caspase-9， Bax， and Cyt C （P<0.05，P<0.01）， and elevated the LC3Ⅱ/LC3Ⅰ level （P<0.05，P<0.01）. High-dose THSG enhanced PC12 cell viability （P<0.01）， increased PINK1/LETM1 co-localization （P<0.01）， and reduced mitochondrial calcium （P<0.01）. ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway， reducing the mitochondrial calcium overload， and promoting mitophagy.

The study aimed to construct the second and third generation chimeric antigen receptor T cells (CAR-T) targeting the c-mesenchymal-epithelial transition factor (c-Met) protein, and observe their killing effect on human serous ovarian cancer cell SKOV-3. The expression of MET gene in ovarian serous cystadenocarcinoma, the correlation between MET gene expression and the abundance of immune cell infiltration, and the effect of MET gene expression on the tissue function of ovarian serous cystadenocarcinoma were analyzed by bioinformatics. The expression of c-Met in ovarian cancer tissues and adjacent tissues was detected by immunohistochemical staining. The second and third generation c-Met CAR-T cells, namely c-Met CAR-T(2G/3G), were prepared by lentivirus infection, and the cell subsets and infection efficiency were detected by flow cytometry. Using CD19 CAR-T and activated T cells as control groups and A2780 cells with c-Met negative expression as Non target groups, the kill efficiency on SKOV-3 cells with c-Met positive expression, cytokine release and cell proliferation of c-Met CAR-T(2G/3G) were explored by lactate dehydrogenase (LDH) release, ELISA and CCK-8 respectively. The results showed that MET gene expression was significantly up-regulated in ovarian cancer tissues compared with normal tissues, which was consistent with the immunohistochemistry results. However, in all pathological stages, there was no obvious difference in MET expression and no correlation between MET gene expression and the race and age of ovarian cancer patients. The second generation and third generation c-Met CAR-T cells were successfully constructed. After lentivirus infection, the proportion of CD8⁺ T cells in c-Met CAR-T(2G) was upregulated, while there was no significant change in the cell subsets of c-Met CAR-T(3G). The LDH release experiment showed that the kill efficiency of c-Met CAR-T(2G/3G) on SKOV-3 increased with the increase of effect-target ratio. When the effect-target ratio was 20:1, the kill efficiency of c-Met CAR-T(2G) reached (42.02 ± 5.17)% (P < 0.05), and the kill efficiency of c-Met CAR-T(3G) reached (51.40 ± 2.71)% (P < 0.05). ELISA results showed that c-Met CAR-T released more cytokine compared to CD19 CAR-T and activated T cells (P < 0.05). Moreover, the cytokine release of c-Met CAR-T(3G) was higher than c-Met CAR-T(2G) (P < 0.01). The CCK-8 results showed that after 48 h, the cell number of c-Met CAR-T(2G) was higher than that of c-Met CAR-T(3G) (P < 0.01). In conclusion, both the second and third generation c-Met CAR-T can target and kill c-Met-positive SKOV-3 cells, with no significant difference. c-Met CAR-T(2G) has stronger proliferative ability, and c-Met CAR-T(3G) releases more cytokines.
Humans ; Female ; Ovarian Neoplasms/immunology* ; Proto-Oncogene Proteins c-met/metabolism* ; Receptors, Chimeric Antigen/immunology* ; Cell Line, Tumor ; Cystadenocarcinoma, Serous/immunology* ; T-Lymphocytes/immunology*

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome