Objective:To investigate the expression of KCTD8 gene in breast ductal carcinoma and its correlation with clinical factors and prognosis.Methods:Immunohistochemistry technology(IHC)were employed to detect protein expression levels of KCTD8 in 27 pairs of breast ductal carci-noma and its paired adjacent tissues.Analyzing the correlation between changes in KCTD8 expres-sion of protein and clinical factors using statistical techniques.RNA expression and methylation data of breast cancer(including intraductal cancer)were analysed from TCGA database.Result:The pro-tein expression of KCTD8 gene in 27 pairs of breast ductal carcinoma tissues showed a decreasing trend compared to adjacent tissues(P＜0.05),and the decreased expression level of protein was cor-related with the tumor size of patients(P＜0.05).The analysis results of the TCGA database indicate that the expression and hypemethylation of KCTD 8 gene in breast cancer(including intraductal can-cer)tissues affected the prognosis of patients.Conclusion:The reduced protein expression level of KCTD8 gene in breast ductal carcinoma may be involved in the development and affect the prog-nosis of patients.

Objective: To examine the efficacy and safety of laparoscopic surgery for gallbladder carcinoma. Methods: The data of 197 gallbladder carcinoma patients admitted at Peking Union Medical College Hospital between January 2012 and September 2022 were analyzed retrospectively. There were 86 males and 111 females,with age of (64.4±9.8)years(range:35 to 89 years). Patients were divided into laparoscopic group(n=53) and open group(n=144) according to different surgical methods. The general information of the two groups were matched by propensity score matching,and the clinical data and prognosis were compared between the two groups. Categorical variables were analyzed using χ² test or Fisher's exact test,as appropriate. Continuous variables with and without normal distribution were analyzed using t-test and Mann-Whitney U test,respectively. Kaplan-Meier curves with Log-rank test were used to analyze the cumulative survival rates. Results: Forty-eight pairs of patients were matched successfully. There was no difference in general information,cholecystolithiasis,partial hepatectomy,and tumor stage between two groups(all P>0.05). The laparoscopic group had shorter operation time(t=-3.987,P<0.01),less bleeding(Z=-4.862,P<0.01),shorter total(Z=-5.009,P<0.01) and postoperative(Z=-5.412,P<0.01) hospital stay. Seventeen patients had postoperative complications. According to the Clavien-Dindo system,there were 4,11,1,and 1 patient with grade Ⅰ,Ⅱ,Ⅲa,and Ⅲb,respectively. All complications were improved after active treatment. After a median follow-up of 24(36) months(range:3 to 130 months),56 patients(58.3%) survived without tumor,7 patients(7.3%) survived with tumor,and 33 patients(34.4%) died. According to the Kaplan-Meier curves,there was no significant difference between laparoscopic and open groups in disease free(χ²=0.399,P=0.528) and overall(χ²=0.672,P=0.412) survival rates. Conclusions: The laparoscopic surgery is safe and effective in selected patients with gallbladder carcinoma. It can reduce surgical trauma and enhance patient recovery without increasing complication. Its prognosis is similar to that of open surgery.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*

Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β₂AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp₈)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.
Adrenergic Agents/pharmacology* ; Apoptosis Regulatory Proteins/pharmacology* ; Bone Diseases, Metabolic/metabolism* ; Humans ; Liposomes ; MicroRNAs/genetics* ; Nanoparticles ; Osteoclasts ; Osteogenesis/physiology* ; RNA-Binding Proteins/pharmacology*

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

OBJECTIVE: To evaluate the efficacy of plasma exchange therapy on crescentic IgA nephropathy (IgAN). METHODS: A retrospective analysis was performed in a cohort of patients with crescentic IgAN from January 2012 to September 2020 at 9 sites across China. Clinical and pathological data, as well as therapeutic regimens, were collected. In order to minimize the effect of potential confounders in baseline characteristics, propensity score matching using a 1 ∶1 ratio nearest neighbor algorithm was performed between the adjunctive plasma exchange therapy group and the intensive immunosuppressive therapy group. The primary outcome was end-stage of kidney disease (ESKD). Kaplan-Meier method was used to compare the difference in renal survival between the two groups. RESULTS: A total of 95 crescentic IgAN patients with acute kidney disease were included in this study, including 37 (38.9%) patients receiving adjunctive plasma exchange therapy, and 58 (61.1%) patients receiving intensive immunosuppressive therapy. In the whole cohort, the baseline eGFR was 12.77 (7.28, 21.29) mL/(min·1.73 m²), 24-hour urinary protein quantification was 5.9 (4.0, 8.9) g, and crescent percentage was 64.71% (54.55%, 73.68%). In the study, 23 patients in each group were matched after propensity score matching The median follow-up time was 7 (1, 26) months. As a whole, 29 patients (63.0%) reached ESKD, including 16 patients (69.6%) in the adjunctive plasma exchange therapy group and 13 (56.5%) patients in the intensive immunosuppressive therapy group.. There were no stastical difference between the two groups in terms of baseline eGFR [14.30 (9.31, 17.58) mL/(min·1.73 m²) vs. 11.45 (5.59, 20.79) mL/(min·1.73 m²)], 24-hour urinary protein (7.4±3.4) g vs. (6.6±3.8) g, crescent percentage 64.49%±13.23% vs. 66.41%±12.65% and the proportion of patients received steroid therapy[23 (100.0%) vs. 21 (91.3%)] (All P>0.05). Kaplan-Meier survival analysis demonstrated that there was no significant difference in renal survival rate between the two groups (Log-rank test, P=0.933). CONCLUSION The adjunctive plasma exchange therapy in addition to conventional intense immunosuppressive therapy did not additionally improve the prognosis of crescentic IgA nephropathy.
Cohort Studies ; Glomerulonephritis, IGA/pathology* ; Humans ; Kidney Failure, Chronic/therapy* ; Plasma Exchange ; Prognosis ; Retrospective Studies ; Steroids/therapeutic use*

Objective:To analyze the clinical characteristics and short-term prognosis of patients with acute asthmatic attack and comorbid bronchiectasis.Methods:The data of patients hospitalized for acute asthmatic attack in the Department of Respiratory and Critical Care Medicine of Peking University Third Hospital from January 1, 2012 to December 31, 2021 were retrospectively collected and analyzed. According to whether or not co-existing with bronchiectasis, all the patients were divided into asthmatic with bronchiectasis group and asthmatic without bronchiectasis group. Then the general conditions, comorbidities, pulmonary function test, grades of asthma severity, laboratory examination and in-hospital short-term prognosis of two groups were analyzed.Results:A total of 580 hospitalized patients with acute asthma attack were included, of which 132 cases (22.76%) were classified into asthmatic with bronchiectasis group and 448 cases (77.24%) were classified into asthmatic without bronchiectasis group. Co-existing with obsolete pulmonary tuberculosis and anxiety/depression in asthmatic with bronchiectasis group were more common than that in asthmatic without bronchiectasis group (13.64% vs 5.36%; 7.58% vs 2.68%) (both P<0.05). The pre-bronchodilator forced vital capacity (FVC) and its percentage to the predicted value (FVC%pred), forced expiratory volume in 1 second (FEV 1) and its percentage to the predicted value (FEV 1%pred), FEV 1/FVC and post-bronchodilator FEV 1 in asthmatic with bronchiectasis group were lower than those in the asthmatic without bronchiectasis group [2.44 (1.90, 3.01) vs 2.69 (2.10, 3.68) L, 1.55 (1.13, 2.00) vs 1.78 (1.25, 2.52) L, 70.14% (67.39%, 85.92%) vs 79.63% (70.00%, 89.52%), 70.00% (54.38%, 78.11%) vs 70.00% (61.47%, 85.00%), 61.57% (56.29%, 73.03%) vs 66.67% (60.00%, 75.00%), 1.72 (1.21, 2.18) vs 1.89 (1.37, 2.55) L] (all P<0.05). In previous year, the proportion of patients receiving hospitalization due to acute asthmatic attack in asthmatic with bronchiectasis group was higher than that in asthmatic without bronchiectasis group (15.15% vs 8.93%) ( P<0.05). The peak months of hospitalization due to acute asthmatic attack in asthmatic with bronchiectasis group were April, July and October, and the peak months in asthmatic without bronchiectasis group were April and September. The length of hospital stay was longer and the proportion of patients receiving invasive ventilation was higher in asthmatic with bronchiectasis group than those in asthmatic without bronchiectasis group [10.06 (7.62, 13.94) vs 9.95 (7.15, 13.76) d; 5.30% vs 2.01%] (both P<0.05). The risk factors for invasive mechanical ventilation in asthmatic patients with acute attack during hospitalization were co-existing with bronchiectasis, smoking, high level of partial pressure of carbon dioxide in arterial blood, serum creatinine and creatine kinase. Conclusion:Asthma patients with comorbid bronchiectasis have more frequent acute attack, a longer hospitalization due to acute asthmatic attack and a higher probability of invasive ventilation during hospitalization.

OBJECTIVE: To observe the effect of intradermal needling combined with heat-sensitive moxibustion for moderate to severe cancer pain. METHODS: A total of 60 patients with moderate to severe cancer pain were randomly divided into an observation group and a control group，30 cases in each one. In the control group，opioids were taken to relief pain according to the three-step analgesic method of World Health Organization. On the base of the treatment as the control group, intradermal needling combined with heat-sensitive moxibustion were applied at Neiguan (PC 6), Hegu (LI 4), Zusanli (ST 36), Taichong (LR 3), etc. in the observation group, 14 days of treatment were required. The equivalent morphine consumption at the first day and whole course, the scores of cancer quality of life questionnaire-C30 (QLQ-C30) and Hamilton anxiety scale before and after treatment, and the adverse reaction rate were compared in the two groups. The total analgesic effective rate was evaluated. RESULTS: The total analgesic effective rate was 93.3% (28/30) in the observation group, higher than 73.3% (22/30) in the control group ( CONCLUSION Intradermal needling combined with heat-sensitive moxibustion can reduce the dose of opioids, improve the quality of life, relief the anxiety in patients with moderate to severe cancer pain, and reduce the incidence of common adverse reaction of opioids.
Acupuncture Points ; Cancer Pain/therapy* ; Hot Temperature ; Humans ; Moxibustion ; Neoplasms/therapy* ; Pain ; Quality of Life ; Treatment Outcome