BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVE: To explore the possible effects and mechanism of Zhizhu Decoction (ZZD) on the pathophysiology of slow transit constipation (STC). METHODS: A total of 54 C57BL/6 mice was randomly divided into the following 6 groups by a random number table, including control, STC model (model), positive control, and low-, medium- and high-doses ZZD treatment groups (5, 10, 20 g/kg, namely L, M-, and H-ZZD, respectively), 9 mice in each group. Following 2-week treatment, intestinal transport rate (ITR) and fecal water content were determined, and blood and colon tissue samples were collected. Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate the morphology of colon tissues and calculate the number of goblet cells. To determine intestinal permeability, serum levels of lipopolysaccharide (LPS), low-density lipoprotein (LDL) and mannose were measured using enzyme-linked immunosorbent assay (ELISA). Western blot analysis was carried out to detect the expression levels of intestinal tight junction proteins zona-occludens-1 (ZO-1), claudin-1, occludin and recombinant mucin 2 (MUC2). The mRNA expression levels of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4, IL-10 and IL-22 were determined using reverse transcription-quantitative reverse transcription reaction. Colon indexes of oxidative stress were measured by ELISA, and protein expression levels of colon silent information regulator 1/forkhead box O transcription factor 1 (SIRT1/FoxO1) antioxidant signaling pathway were detected by Western blot. RESULTS: Compared with the model group, ITR and fecal moisture were significantly enhanced in STC mice in the M-ZZD and H-ZZD groups (P<0.01). Additionally, ZZD treatment notably increased the thickness of mucosal and muscular tissue, elevated the number of goblet cells in the colon of STC mice, reduced the secretion levels of LPS, LDL and mannose, and upregulated ZO-1, claudin-1, occludin and MUC2 expressions in the colon in a dose-dependent manner, compared with the model group (P<0.05 or P<0.01). In addition, ZZD significantly attenuated intestinal inflammation and oxidative stress and activated the SIRT1/FoxO1 signaling pathway (P<0.05 or P<0.01). CONCLUSION ZZD exhibited beneficial effects on the intestinal system of STC mice and alleviated intestinal inflammation and oxidative stress via activating SIRT1/FoxO1 antioxidant signaling pathway in the colon.
Mice ; Animals ; Sirtuin 1/genetics* ; Antioxidants ; Occludin ; Lipopolysaccharides ; Claudin-1 ; Mannose ; Mice, Inbred C57BL ; Constipation/drug therapy* ; Inflammation ; Signal Transduction

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ²=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ²<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ²<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ²=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ²=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.
Male ; Humans ; Female ; Young Adult ; Adult ; Helicobacter Infections ; Helicobacter pylori ; Bismuth ; Anti-Bacterial Agents/therapeutic use* ; Amoxicillin/adverse effects* ; Drug Therapy, Combination ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Humans ; Floods ; Paraffin ; Paraffin Embedding

BACKGROUND: The efficiency of the target versus sub-target dose of renin-angiotensin system inhibitors (RASIs) in elderly patients with heart failure (HF) with reduced ejection fraction (HErEF) remains unclear. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from database inception through March 2022 for randomized controlled trials (RCTs) and observational studies considering the effect of the target versus sub-target dose of RASIs on survival in elderly patients (≥ 60 years) with HErEF. The primary outcome was all-cause mortality. The secondary outcomes were cardiac mortality, HF hospitalization, and the composite endpoint of mortality or HF hospitalization. A meta-analysis was conducted to generate combined hazard ratio (HR) and 95% CI. RESULTS: Seven studies (two RCTs and five observational studies) enrolling 16,634 patients were included. A pooled analysis suggested that the target versus sub-target dose of RASIs led to lower rates of all-cause mortality (HR = 0.92, 95% CI: 0.87-0.98, I² = 21%) and cardiac mortality (HR = 0.93, 95% CI: 0.85-1.00, I² = 15%) but not reduced rates of HF hospitalization (HR = 0.94, 95% CI: 0.88-1.01, I² = 0) and the composite endpoint (HR = 1.03, 95% CI: 0.91-1.15, I² = 51%). However, the target dose of RASIs was associated with a similar primary outcome (HR = 0.85, 95% CI: 0.64-1.14, I² = 0) in a subgroup of very elderly patients > 75 years of age. CONCLUSIONS Our analysis suggests that the target dose of RASIs has a better survival benefit in elderly patients with HFrEF compared to the sub-target dose of RASIs. However, the sub-target dose of RASIs is associated with a similar mortality rate in very elderly patients > 75 years of age. Future high-quality and adequately powered RCTs are warranted.

Clinical practice using associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) or its modified procedures in treatment of primary hepatocellular carcinoma(HCC) with insufficient future liver remnant(FLR) in the past 10 years has failed to meet our expectations both in achieving decreased perioperative complications and mortality.The efficacy of ALPPS in improving long-term survival outcome of HCC still remains poor.Due to the trauma of two surgery within a short period,and patients with inadequate FLR are all diagnosed at advanced disease stages,ALPPS can only achieve surgical rather than biological tumor-curability.Previous studies have demonstrated comparable 5-year survival rates between early and advanced stages of HCC who underwent regional treatments.Therefore,tumor biological conversion is the key strategy prior to liver remnant volume conversion in improving treatment outcomes for HCC patients with insufficient FLR.Target therapy,immunotherapy together with locally treatment were expected to improve the conversion efficacy.Looking back at the development of ALPPS for the last decade,the rapid proliferation of FLR should be passed on,while the technology costs high risks and result in poor long-term outcome must be cautiously selected.
Carcinoma, Hepatocellular/surgery* ; Hepatectomy ; Humans ; Ligation ; Liver ; Liver Neoplasms/surgery* ; Portal Vein/surgery* ; Technology ; Treatment Outcome

Objective: To observe the intervention effect of auricular point sticking on dry eye in myopia patients after small-incision lenticule extraction (SMILE) surgery.Methods: This was a prospective randomized controlled study conducted among the myopia patients who received SMILE surgery at Eye and ENT Hospital of Fudan University. The post-SMILE operation patients who screened by the inclusion and exclusion criteria were randomized into a control group and a treatment group. Patients in the control group were given 0.1％ fluorometholone and 0.5％ carboxymethylcellulose sodium eye drops, while the treatment group was given additional unilateral auricular point sticking for 1 month. The patients were estimated using ocular surface disease index (OSDI), Schirmer tear test-1 (STT-1), tear film break-up time (TF-BUT), corneal fluorescein staining (CFS) score, corneal sensitivity (CS) and visual quality (VQ) at 1 d, 1 week and 1 month after surgery; the changes in anxiety and depression were also observed in the patients. Results: Compared with the first day after operation, CS in the nasal region was improved in the treatment group, and the VQ score increased in the control group patients at 1 week after operation (both P<0.05); at 1 month after operation, the TF-BUT increased, CFS score decreased, CS in the central and nasal regions increased (all P<0.05), and VQ score increased (P<0.01) in the treatment group, and the CS in the central, upper, lower and nasal regions were improved (all P<0.05), and VQ score increased (P<0.01) in the control group. The between-group comparison showed that the differences in the change of TF-BUT were statistically significant at 1 week and 1 month after surgery, respectively (both P<0.05). Conclusion: Auricular point sticking therapy can increase the TF-BUT and accelerate the repair of ocular surface function in post-SMILE patients.

Objective::To observe effect of addition and subtraction therapy of Huaihuasan combined with Taohuatang to ulcerative colitis with cold-heat complicated syndrome at active stage, and to study regulation effect to immune function and inflammatory response. Method::One hundred and twelve patients were randomly divided into control group and observation group by random number table. Patients with light and middle symptoms in control group got mesalazine slow release tablets, 1.0 g/time, 3 times/days, patients with severe symptoms or whose symptoms were not changed after getting for 4 weeks in control group got prednisone acetate tablets, 0.75 mg·kg^-1·d^-1 for 3 times. Based on the treatment in control group, patients in observation group added Huaihuasan combined with Taohuatang, 1 dose/day. The course of treatment was 4 weeks. At remission period, mesalazine slow release tablets were used for maintain long-term maintenance therapy, 0.5 g/times, 3 times/days. Scores of disease activities were graded by improvement mayo, and clinical remission and clinical efficacy were recorded, scores of cold-heat complicated syndrome, mucous membrane under enteroscopy and histology of mucosa belongs to Geboes were graded. And levels of tumor necrosis factor-α(TNF-α) in peripheral blood, interleukin-8 (IL-8), IL-10, T lymphocyte subsets (CD4⁺, CD8⁺), and adverse reactions, 6 months' follow-up and recurrence were also be recorded. Result::Therapeutic effect of traditional Chinese medicine syndromes were analyzed by rank sum test, which in observation group was better than that in control group (Z=1.915, P<0.05). Clinical effect in observation group was 98.04%(50/51) higher than 84.00%(42/50) in control group, clinical remission rate was 94.12%(48/51) higher than 78.00%(39/50) in control group, and mucosal healing rate was 96.08%(49/51) higher than 82.00%(41/50) in control group (P<0.05). Scores of mayo, cold-heat complicated syndrome, colonic mucosa and index scores of Geboes were all lower than those in control group (P<0.01). And levels of TNF-α, IL-8 and CD8⁺ were lower than those in control group (P<0.01), and levels of IL-10, CD4⁺ and CD4⁺ /CD8⁺ were higher than those in control group (P<0.01). Recurrence rate during 6 months in observation group was 10.42%(5/48) lower than 30.77%(12/39) in control group (χ²=5.669, P<0.05), as for adverse reactions, there was no significant difference between two groups. Conclusion::Huaihuasan combined with Taohuatang can induce UC to remission period, inhibit the activity of disease, alleviate clinical symptoms, regulate immune function and expression of inflammatory factors, alleviate inflammatory reaction, promote intestinal mucosal healing, and can maintain clinical remission and reduce recurrence. The clinical efficacy is superior to that of 5-ASA/glucocorticoid in Western medicine.