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

Objective To assess the efficacy of a novel inguinal tourniquet in healthy individuals and to investigate the relationship between localized inguinal compression and femoral artery blood flow occlusion.Methods A self-controlled study was conducted.From November 9 to November 30,2024,11 volunteers were recruited at the Third Medical Center of Chinese PLA General Hospital.Three compression methods--finger pressure,a novel groin tourniquet,and a SAM junction tourniquet(SJT)—were applied bilaterally to the inguinal region until distal blood flow signals disappeared.Each compression method was tested in 22 trials with a 5-minute interval between operations.Differences in hemostatic efficacy between bilateral inguinal regions and across compression methods were compared.Subsequently,the novel tourniquet was incrementally pressurized in 120 mmHg multiples using an integrated pressure device to analyze trends in popliteal artery blood flow velocity.Observational indicators included the internal pressure of the tourniquet pressurization device,peak systolic velocity(PSV)of popliteal artery,inguinal surface pressure magnitude,inguinal surface pressure distribution,and pain scores(assessed using a single-dimensional numerical rating scale).Results No statistically significant difference was observed in the minimum pressure required to occlude femoral artery blood flow bilaterally(P>0.05).The success rates of femoral artery blood flow occlusion at the inguinal region were 100%for the novel inguinal tourniquet,SJT,and finger pressure.The novel inguinal tourniquet induced the highest pain scores,ranging from 5 to 8.A significant reduction in PSV of popliteal artery was noted when the intra-tourniquet pressure reached 360 mmHg and 480 mmHg(P<0.05),with a 95%hemostasis efficacy observed within the range of 360-600 mmHg.No significant association was observed between the recovery of popliteal artery blood flow after limb movement and inguinal pressure distribution(P>0.05).The PSV of popliteal artery exhibited the strongest negative correlation with the average pressure within the inguinal compression area(r=-0.79,P<0.001),with a linear regression fitting line of y=69.69-0.13x(P<0.001,R2=0.58).Conclusions The novel inguinal tourniquet effectively occludes femoral artery blood flow within a pressure range of 360-600 mmHg,accompanied by moderate-to-severe pain.Its hemostatic mechanism mainly relies on increasing the mean pressure within the inguinal compression area.

Grounded in the theory of "all marrows dominated by brain", this study explored the therapeutic mechanism of Zuogui Pills in modulating the oxytocin(OXT)/oxytocin receptor(OXTR) feed-forward loop in the treatment of postmenopausal osteoporosis(PMOP). A PMOP rat model was established using ovariectomy, and 70 Sprague-Dawley female rats were randomly divided into the following groups: sham operation group, model group, estradiol group(17β-estradiol, 0.05 mg·kg~(-1)·d~(-1)), Zuogui Pills low, medium, and high dose groups(0.2, 0.4, 0.8 g·kg~(-1)·d~(-1), respectively), and an antagonist group(atosiban 0.9 mg·kg~(-1)·d~(-1) + 17β-estradiol 0.05 mg·kg~(-1)·d~(-1) + Zuogui Pills 0.4 g·kg~(-1)·d~(-1)). After 12 weeks of model establishment, treatment was administered by gavage once daily for another 12 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of estrogen(E_2), OXT, tartrate-resistant acid phosphatase(TRACP-5b), and bone alkaline phosphatase(BALP). Histopathological changes in the left distal femur were observed through hematoxylin and eosin(HE) staining. Micro-computed tomography(micro-CT) was used to analyze the microstructure of the right distal femur. Western blot was employed to detect the expression levels of OXTR, small GTP-binding protein Ras, Raf1 proto-oncogene(Raf1), mitogen-activated protein kinase kinase 1/2(MEK1/2), and extracellular signal-regulated kinase 1/2(ERK1/2), and their phosphorylated forms in tibial tissues. Compared with the model group, the Zuogui Pills medium and high dose groups showed significantly increased levels of E_2, OXT, and BALP, with a notable decrease in TRACP-5b levels. Morphologically, the trabeculae in the left distal femur were more tightly arranged. The fibrous structure in the right distal femur was significantly improved in the Zuogui Pills high dose group. Additionally, the expression of OXTR, Ras, p-Raf1, p-MEK1/2, and p-ERK1/2 proteins in tibial tissues was significantly increased. The therapeutic effect of the Zuogui Pills high dose group was partially inhibited when an OXTR antagonist was administered. These findings suggest that Zuogui Pills can regulate the OXT/OXTR feed-forward loop, activate the phosphorylation of the downstream Ras/Raf1/MEK/ERK signaling pathway, and ultimately improve bone mineral density, thereby exerting therapeutic effects in PMOP.
Animals ; Rats, Sprague-Dawley ; Rats ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Oxytocin/genetics* ; Receptors, Oxytocin/genetics* ; Humans ; Osteoporosis, Postmenopausal/genetics* ; Bone and Bones/drug effects* ; Brain/drug effects* ; Bone Marrow/drug effects*

OBJECTIVE: To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion. METHODS: Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively. RESULTS: The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984). CONCLUSION The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans ; Lymphoma, T-Cell, Peripheral/pathology* ; Prognosis ; Retrospective Studies ; Central Nervous System Neoplasms/pathology* ; Neoplasm Invasiveness ; Male ; Female ; Central Nervous System/pathology* ; Middle Aged ; Adult

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Objective To investigate the effect of varying ureteral wall thickness(UWT)at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy(URL).Methods The clinical data of 164 patients with ureteral stones in our hospital were retrospectively analyzed.According to different UWT,the patients were divided into the mild thickening group(84 cases,UWT<3.16 mm),the moderate thickening group(31 cases,UWT 3.16 to 3.49 mm),and the severe thickening group(49 cases,UWT>3.49 mm),and the differences of clinical related indicators among the three groups were compared.Results The incidence of postoperative renal colic and leukocyte disorder in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,and the differences were statistically significant(P<0.05).The postoperative catheterization time in the mild thickening group and the moderate thickening group were shorter than that in the severe thickening group,and the incidences of secondary lithotripsy,residual stones and stone return to kidney in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,with statistically significant differences(P<0.05).The length of hospital stay and hospitalization cost in the mild thickening group and the moderate thickening group were shorter/less than those in the severe thickening group,with statistically significant differences(P<0.05).Conclusion With the increase of UWT(especially when UWT>3.49 mm),the incidence of postoperative complications and hospitalization cost of URL increase to varying degrees,and the surgical efficacy decreases.In clinical work,UWT measurement holds potential value in predicting the surgical efficacy and complications of URL.

Objective To establish a method to identify an unknown substance based on the combined use of gas chromatography-quadrupole time-of-flight mass spectrometry(GC-QTOF-MS),ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q/Orbitrap HRMS)and nuclear magnetic resonance(NMR)techniques.Methods The unknown substance was dissolved in methanol and was detected by GC-QTOF-MS and UPLC-Q/Orbitrap HRMS,and was dissolved in methanol-d4 to be detected by NMR.Results The main characteristics ion peaks of components with retention time of 9.67 min in GC-QTOF-MS measured were 84.080 8,110.999 7,128.107 0(base peak),138.994 7,etc.The protonated molecular ion peak m/z in UPLC-Q/Orbitrap HRMS was 268.109 3.It was inferred that the unknown substance was an analog of the syn-thetic cathinone substance 2-methyl-1-[4-(methylthio)phenyl]-2-morpholinopropan-1-one(MTMP)by comparing the mass spectrum information and molecular structure of MTMP.NMR analysis confirmed it as a novel N-morpholine substituted synthetic cathinone substance 1-(4-chlorophenyl)-2-methyl-2-morpholinopropan-1-one(CMMP).Conclusion The method established in this study can be used for structural confirmation of CMMP.

Humans ; Floods ; Paraffin ; Paraffin Embedding

Objective: To explore the characteristics, patterns of multimorbidity and the impact on quality of life and the prognosis of middle-aged and elderly patients with chronic obstructive pulmonary disease (COPD). Methods: This is a cross-sectional study. From January 2012 to December 2021, 939 middle-aged and elderly COPD patients hospitalized in Beijing Hospital were selected by the convenient sampling method. The basic data of patients and the date of 16 common chronic diseases were collected. Patterns of multimorbidity were depicted by cluster analysis. Generalized linear regression model and logistic regression were used to evaluate the multimorbidity patterns and their prognosis. Results: At least one multimorbidity existed among 93.40% of COPD patients, and the median number of multimorbidity was 3. The top five multimorbidity among the patients were hypertension (57.93%, 544/939), coronary heart disease (33.76%,317/939), heart failure (31.95%,300/939), hyperlipidemia (31.63%,297/939) and arrhythmia (27.37%,257/939). Four multimorbidity patterns were identified, cardiometabolic and metabolic multimorbidity, kidney disease multimorbidity, respiratory-digestive-tumor multimorbidity and other multimorbidity. Cardiometabolic and metabolic multimorbidity was most common (590/939, 62.83%). Compared with non-cardiometabolic and metabolic multimorbidity, the incharge ADL score of patients with this multimorbidity decreased by 7 points (95%CI:-11.22- -3.34), Correspondingly, patients with kidney disease multimorbidity decreased by 14 points (95%CI:-24.12- -3.30) on the incharge score. The presence or absence of kidney disease multimorbidity had the greatest impact on discharge score, which was reduced by 12 points in comparison with patients without this multimorbidity (95%CI:-22.43- -2.40). ICU admission is mostly affected by the presence of cardiometabolic and metabolic multimorbidity (OR=2.44, 95%CI: 1.51-3.92) and kidney disease multimorbidity (OR=2.58, 95%CI: 1.01-6.60). The risk of death is the highest for cardiometabolic and metabolic multimorbidity (OR=2.24, 95%CI: 1.19-4.21). Conclusion: Multimorbidity is common in COPD patients. The most common pattern is cardiometabolic and metabolic multimorbidity. Cardiometabolic and metabolic multimorbidity and kidney disease multimorbidity significantly affect the quality of life and often associate with a poor prognosis.
Aged ; Middle Aged ; Humans ; Multimorbidity ; Inpatients ; Prevalence ; Cross-Sectional Studies ; Quality of Life ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Chronic Disease

Objective: To exploring the clinical features of SF3B1-mutated myelodysplastic syndrome with excess blasts (MDS-EB) and analyzing the association between SF3B1 mutation, and efficacy and prognostic significance for patients with MDS-EB. Methods: This was a retrospective case series study. The clinical data of 266 patients with MDS-EB diagnosed in the First Affiliated Hospital of Zhengzhou University between April 2016 and November 2021 were analyzed. The observed indicators included blood routine counts, mutated genes, overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and leukemia-free survival (LFS). The Kaplan-Meier method was used to depict the survival curves. The Log-rank test method was equally used to compare survival across groups and performed the Cox proportional hazard regression model for prognostic analysis. Results: In 266 patients with MDS-EB, 166 (62.4%) were men, and the median age was 57 (17-81) years. Moreover, there were included 26 and 240 patients in the SF3B1-mutated and SF3B1 wild-type groups. Patients in the SF3B1-mutated group were older [median age 65 (51, 69) years vs. 56 (46, 66) years, P=0.033], had higher white blood cell (WBC) counts [3.08 (2.35, 4.78) × 10⁹/L vs. 2.13 (1.40, 3.77) × 10⁹/L], platelet (PLT) counts [122.5 (50.5, 215.0) ×10⁹/L vs. 49.0 (24.3, 100.8) × 10⁹/L], absolute neutrophil counts (ANC) [1.83 (1.01, 2.88) × 10⁹/L vs. 0.80 (0.41, 1.99) × 10⁹/L]and occurrence of DNMT3A mutation [23.1% (6/26) vs. 6.7% (16/240)] (all P<0.05). The ORR were similar in both groups after 2 and 4 cycles of therapy (P=0.348, P=1.000). Moreover, the LFS (P=0.218), PFS (P=0.179) and OS (P=0.188) were similar across the groups. Univariate Cox analysis revealed that SF3B1 mutation did not affect the prognosis of patients with MDS-EB (OS: P=0.193; PFS: P=0.184). Conclusions: Patients with SF3B1 mutation were older, with greater WBC, PLT, and ANC, and SF3B1 mutation easily co-occurred with DNMT3A mutation. From this model, there were no significant differences in efficacy and survival of MDS-EB with or without SF3B1 mutation.
Aged ; Female ; Humans ; Male ; Middle Aged ; Leukocytes ; Mutation ; Myelodysplastic Syndromes/diagnosis* ; Phosphoproteins/genetics* ; Prognosis ; Retrospective Studies ; RNA Splicing Factors/genetics* ; Adolescent ; Young Adult ; Adult ; Aged, 80 and over