AIM: To investigate the implication of respiratory microbiology on the efficacy of PD-1 inhibitors monotherapy for patients with NSCLC. METHODS: This study was designed as a retrospective study, fifty-eight patients with previously-treated advanced NSCLC who were received PD-1 monotherapy from October 2018 to October 2021 were included. The PD-1 inhibitors were consisted of camrelizumab, sintilimab and pembrolizumab. Additionally, the basic demographic data, therapeutic efficacy data, survival prognosis and adverse reactions during the PD-1 inhibitors treatment were collected and analyzed through the patients' medical records of the department and the electronic medical record system of the hospital. Furthermore, deep induced sputum specimens of the patients before treatment with PD-1 inhibitor were collected. And the respiratory microbiology of 58 samples were detected using 16S rRNA gene sequencing method. The index of respiratory microbiology α diversity was analyzed, and the correlation analysis was performed with the efficacy and prognosis of patients. RESULTS: A total of 58 patients with advanced NSCLC met the study's screening criteria and were evaluable for efficacy and safety profile. Efficacy data suggested that the objective response rate (ORR) and disease control rate (DCR) of the patients who received PD-1 inhibitors was 19.0%(95% CI: 9.9%-31.4%) and 55.2% (95% CI: 41.5%-68.3%). Furthermore, prognostic data obtained from follow-up indicated that the median PFS of the 58 patients with advanced NSCLC was 3.2 months (95% CI: 2.29-4.11) and the median OS was 10.5 months (95% CI: 5.58-15.43). Regarding the exploratory analysis between efficacy and respiratory microbiology, the 58 patients with NSCLC were divided into high α diversity group (group H) and low α diversity group (group L) according to Shannon diversity index of respiratory microecology detection. And the association analysis suggested that the ORR of patients with group H and group L was 23.3% and 17.9%(P c 0.380), respectively. Furthermore, prognostic analysis indicated that the median PFS of patients with group H and group L was 3.8 and 2.8 months, respectively, which was statistically significant (P c 0.034). CONCLUSION: PD-1 inhibitors monotherapy demonstrated preliminary efficacy and prognosis as subsequent line treatment for patients with advanced NSCLC. Patients with higher α -diversity of respiratory microbiology might confer a superior prognosis. And the conclusion should be validated in large sample prospective clinical trials subsequently.

In recent years, immunotherapy with immune checkpoint as the target has made revolutionary breakthroughs in the treatment of a variety of advanced solid tumors. Notwithstanding the impressive long-term therapeutic benefits, their efficacy is limited to a small subset of cancer patients. Some patients experienced drug resistance and immune-related adverse events (irAEs). Immune checkpoint inhibitors (ICIs) primarily include antibodies targeting CTLA-4 and antibodies targeting PD-1 and its ligands. Thus, it is of utmost importance to screen potential biomarkers in populations that may benefit from immunotherapy, to maximize therapeutic benefits. This review summarizes the mechanism of ICIs and its related efficacy biomarker, to better guide the application of immunotherapy in clinical practice.

Objective To investigate the incidence of enteric pathogens causing acute gastroenteritis (AGE) among children to measure the incidence of coinfections,and to compare the clinical characteristics of those infected with one versus multiple agents.Methods A retrospective study was conducted from January 2014 to December 2014.All patients between 1 month and 14 years of age admitted to the Pediatric department with a diagnosis of AGE were eligible for enrollment.Two stool samples for each patient were tested for gastrointestinal pathogens.We summarized the clinical severity of episodes,describing the duration of diarrhea,duration and frequency of vomiting,fever.All patients underwent medical evaluation with estimation of dehydration.Results One or more etiological agents were detected in 3595 out of 4728 patients(76.0％),while we did not detect any etiological agent in 1133 (24.0％).Rotavirus was detected in 1889 (40.0％),adenovirus in 412 (8.7 ％),norovirus in 309 (6.5 ％),verotoxigenic Escherichia coli (VTEC) in 274 (5.8 ％),Salmonella spp.in 276(5.8％),Klebsiella pneumoniae in 123 (2.6％),Shigella spp.in 78 (1.6％),Staphylococcus aureus in 70 (1.5％),C.perfringens in 126(2.7％).In 1370 children out of 4728(29.0％),we found evidence of coinfection.with rotavirus and norovirus was the most common 150 (3.2％),rotavirus and C.perfringens was also common 127(2.7％).Children with coinfection had a more severe clinical presentation.The difference has statistical significance.Conclusion Rotavirus is still the most common pathogen in children with acute diarrhea,followed by NV,adenovirus,Salmonella spp.and VTEC.Rotavirus with norovirus infection was the most common.VTEC combined with three kinds of virus infection had the highest incidence.Children with multiple viral infections were more severe than those of single virus infection in the duration of vomiting and dehydration.There was no significant difference in the duration of fever and diarrhea and the frequency of diarrhea.Children infected by viruses and bacteria had a more severe clinical presentation such as fever,vomiting and diarrhea lasting for a long time,more serious diarrhea and dehydration than those with single bacteria and single virus infection.The difference has no significant difference in degree and duration of diarrhea.

OBJECTIVETo explore the etiology and clinical characteristics of hypoxic hepatitis (HH) in children.

METHODClinical data of 7 patients with HH in Shenzhen Children's Hospital from January 2011 to March 2014 were retrospectively reviewed.

RESULTSeven cases diagnosed as HH, age from 4 months to 11 years, were admitted to pediatric intensive care unit (PICU), and accounted for 0.32% of patients in PICU during the same period. The primary causes of HH were respiratory failure and cardiac shock caused by severe hand-foot-and-mouth disease, fulminant myocarditis, infant muggy syndrome . Serologic tests for hepatitis B virus, hepatitis C virus, as well as serum antibody and DNA for Epstein-Barr virus and cytomegalovirus were all negative. There was an increase of alanine aminotransferase (ALT) (≥20 time supper limit of normal (ULN), the highest ALT was more than 130 times ULN in all the patients, which was decreased to 2 times ULN from peak within 10 days. There was a significant relationship between ALT and aspartate aminotransferase(AST)in 3 cases(r=1.000, 1.000, and 0.833, respectively, P<0.05), ALT and lactate dehydrogenase (LDH)in 2 cases(r=1.000 and 0.886, respectively, P<0.05), ALT and blood urea nitrogen(BUN)in 1 case(r=1.000, P<0.05), and ALT and creatine kinase(CK)in 1 case(r=0.964, P<0.05). The ALT, AST and LDH returned to normal soon after the primary diseases were controlled.

CONCLUSIONSevere heart failure, hypoxemia, shock, etc. are the leading primary diseases causing HH. The sharp increase in ALT, AST and LDH is the typical laboratory manifestion in HH after the onset, which may decline to normal shortly after the treatment, sometimes complicated with reversible change in BUN or CK.

Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Child ; Child, Preschool ; Creatine Kinase ; Heart Failure ; Hepatitis ; Herpesvirus 4, Human ; Humans ; Hypoxia ; Infant ; L-Lactate Dehydrogenase ; Respiratory Insufficiency ; Retrospective Studies

Objective To investigate the clinicopathologic features and prognostic analysis of intrahepatic mucinous cholangiocarcinoma (IMCC) and intrahepatic cholangiocarcinoma (ICC).Methods The retrospective cohort study was adopted.The clinicopathological data of 20 patients with IMCC and 51 patients with ICC who were admitted to the Fujian Provincial Hospital from March 2003 to March 2014 were collected.The observation indicators included (1) clinicopathologic features:gender,age,clinical symptoms (fever,jaundice,abdominal pain and peritoneal effusion),preoperative laboratory examination [alanine transaminase (ALT),aspartate transaminase (AST),direct bilirubin (DBil),carcinoembryonic antigen (CEA),CA19-9 and alphafetoprotein (AFP)],operation methods (radical resection,palliative resection) and pathological features (tumor location,lymph node metastasis,vascular invasion and pathological stage).(2) The follow-up of outpatient examination and telephone interview was performed to detect the survival of patients up to March 2015.Measurement data with normal distribution were represented as x-± s and comparison between groups was analyzed using t test.Count data were analyzed using the chi-square test.The survival curve was drawn by Kaplan-Meier method,and the survival rate was analyzed using the Log-rank test.Result The numbers of patients with fever,jaundice,elevated level of AST and DBil,lymph node metastasis,vascular invasion and numbers of patients with stage 0,Ⅰ,Ⅱ,Ⅲ,Ⅳ were 13,11,10,11,3,1 and4,6,2,6,2 with IMCC,12,10,9,2,22,36 and 0,14,5,3,29 with ICC,respectively,showing statistically significant differences in the above indicators (x2=10.830,8.639,7.672,25.059,8.036,24.765,26.601,P ＜ 0.05).All the patients were followed up for a median time of 14 months (range,1-118 months).The survival time and 1-,3-,5-year survival rates were (55 ± 8)months,94.4％,44.0％,16.7％ in 20 patients with IMCC and (30 ±6) months,36.5％,12.5％,4.0％ in 51 patients with ICC,respectively,showing a statistically significant difference (x2 =8.126,P ＜ 0.05).Conclusion The patients with MICC are more easily complicated with fever,jaundice and liver dysfunction,while they have less lymph node metastasis and vascular invasion,earlier pathological stage and better prognosis compared with patients with ICC.

Objective To compare the differences of hospital stays,hospitalization costs and effectiveness via keyhole hematoma debridement (KHED) and internal medicine conservative treatment (IMCT) in treating 30-40 mL hypertensive intracerebral hemorrhage.Methods Fifty-eight patients with hypertensive intracerebral hemorrhage whose bleeding was 30-40 mL,admitted to our hospital from January 2014 to September 2015,were chosen in our study;according to the will of the patients and their family members,the patients were divided into KHED group (n=31) and IMCT group (n=27).The differences of hospital stays,hospitalization costs,neurological dysfunction rate at hospital and three months after discharge,and recovery results were compared between the two groups.Results The average hospital stays of KHED group were (7.4±2.3) d and those of IMCT group were (14.5±5.1) d,with significant difference (P=0.012);the hospitalization costs for the two groups were (36 296.28±5292.12)yuan,and (41 769.48±6342.83) yuan,with significant difference (P=0.027).Glasgow outcome scale of KHED group at discharge indicated 29 patients with good recovery and 2 with poor recovery;that of IMCT group indicated 20 with good recovery and 7 with poor recovery,including two with cerebral edema accepted craniotomy operation in second time.Follow-up for three months showed that the KHED group had basic activities of daily living in 16 patients,mild hemiplegia in 11 and severe hemiplegia in 4,and IMCT group had basic activities of daily living in 9 patietns,mild hemiplegia in 13 and severe hemiplegia in 5;significant differences were noted between the two groups (Z=2.499,P=0.001).Conclusion KHED in treatment of 30-40 mL hypertensive intracerebral hemorrhage can shorten hospitalization time,reduce cost,have better prognosis and better short-term and long-term effectiveness than IMCT.

Objective To investigate the factors affecting the depression in elderly patients after surgery. Methods A total of 196 elderly patients (≥60 years old) with surgery in our hospital from January 2013 to January 2015 were investigated by self-rating depression scale ( SDS) . Patients were assigned to the depression group and the normal group according to the SDS score. Logistic regression analyses were used to analyze the related risk factors about postoperative depression.Results There were 104 elderly patients suffered depression after surgery, and the incidence rate of depression was 53. 1%. In the depression group, female patients with postoperative pressure accounted for 38.5%;patients with preoperative depression accounted for 76.7%;patients with malignant disease accounted for accounted for 8.6%;patients with chronic pain accounted for 24%, and all were higher than the normal group (χ2=4.06,8.11,5.40,9.65;P<0.05). Multiple Logistic regression showed that female, chronic pain and preoperative pain were risk factors of postoperative depression ( P<0. 05 ) . Conclusions Elderly patients with high risk of postoperative depression should be given more attention and psychological counseling, to reduce the risk of depression.

Objective: To investigate the effect of tanshinone IIA (TSN) on left ventricular hypertrophy (LVH) and cardiomyocyte apoptosis in spontaneous hypertensive rats (SHRs). Methods: A total of 60 SHRs at 8 weeks of age were randomly divided into 3 group: Blank control group, the rats were sacriifced at 8 weeks, TSN group, the rats were treated with TSN at 1 ml/(kg?d) for 18 weeks and Solvent control group, the rats were treated with the solvent at 1 ml/(kg?d) for 18 weeks. n=20 in each group and 15 rats were used for the experiments. The systolic blood pressure (SBP) and left ventricular mass index (LVMI) were examined, cardiomyocyte’s diameter and surface area were measured by HE staining, the apoptosis rate was evaluated by TUNEL method and the apoptosis related protein expression s of Bcl-2, Bax and p53 were determined by Western blot analysis. Results: ①Compared with Solvent control group, TSN group had decreased LVMI (3.23 ± 0.24) mg/g vs (4.58 ± 0.68) mg/g,cardiomyocyte’s diameter (16.13 ± 1.77) μm vs (27.15 ± 3.52) μm and surface area (230.23 ± 69.37) μm2 vs (490.12 ± 118.96) μm2and decreased apoptosis rate (7.45 ± 1.78) % vs (10.61 ± 2.77) %, allP<0.01.②With NAPDH reference correction, compared with Solvent control group, TSN group presented increased protein expression of Bcl-2 (0.97 ± 0.31) vs (0.40 ± 0.11) and decreased Bax (0.37 ± 0.15) vs (1.81 ± 0.44), decreased p53 (0.83 ± 0.18) vs (2.72 ± 0.28), allP<0.05 or P<0.01. The above indexes were similar between TSN group and Blank control group,P>0.05. Conclusion: TSN could inhibit the development of LVH and decrease the cardiomyocyte apoptosis, which might be via up-regulating the protein expressions of Bcl-2 and down-regulating Bax and p53 in SHRs.

Objective To investigate the effects of brain-derived neurotrophic factor (BDNF) pretreatment on H9c2 myocardial hypoxia/reoxygenation (H/R) injury, and explore its mechanism. Methods The H9c2 myocardial cells were cul?tured in vitro and (95%O2+5%CO2) oxygen cultured 12 h after (95%N2+5%CO2) hypoxia cultured 4 h to establish the H/R model. The cells were divided into normal control group, H/R group, different concentrations (1, 10, 100μg/L) BDNF pre?treatment in H/R groups and TrkB-inhibitor group (with 100μg/L BDNF and 1∶1 000 TrkB inhibitor pre-treatment in H/R group). The cell survival rate was measured by MTT method in different groups. The lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA) and superoxide dismutase (SOD) content and activity were detected after H/R injury. The apoptotic rate of H9c2 myocardial cells were detected by flow cytometry, and the expressions of TrkB, Bcl-2 and Bax protein were detected by Western blot assay. Results Compared with the normal control group, the survival rate of H9c2 myocardial cells was decreased significantly in H/R model group (P < 0.05), LDH, CK and MDA contents were increased and SOD activity was decreased (P<0.05). The cell apoptosis rate was increased significantly (P<0.05). The anti-apoptosis Bcl-2 protein expression was decreased, pro-apoptosis Bax protein expression was increased in H/R model group (P<0.05). Compared with the H/R model group, the cell survival rates of H9c2 myocardial cells were increased after pre-treatment with different concentrations of BDNF (P<0.05);LDH, CK and MDA contents were decreased and SOD activity were in?creased respectively (P < 0.05). The cell apoptotic rates were decreased (P < 0.05). The expressions of TrkB receptor and Bcl-2 protein gradually increased, while the expression of Bax protein was gradually decreased (P<0.05). The role of BDNF was inhibited by TrkB inhibitor. Conclusion BDNF pre-treatment can promote the cell survival rate of H9c2 myocardial cells after H/R injury, which plays a protective role by inhibiting the cell apoptotic rate and maintaining antioxidant capacity, and associates with BDNF-TrkB signaling pathways.

Objective To observe the efficacy and safety of recombinant tissue type plasminogen activa-tor (rt-PA)for the treatment of the patients with wake-up ischemic stroke (WUS)under the guidance of multimode CT. Methods Eighteen patients with WUS (a thrombolytic group)suitable for intravenous thrombolysis after multimode CT imaging screen at the Department of Neurology,Shiyan Hospital of Integrated Traditional and Western Medicine,Hubei Province from October 2012 to October 2014 were enrolled retrospectively. Twenty patients with WUS (a control group)who underwent multimode CT imaging screen were suitable for intravenous thrombolysis,but because of exceeding time window or rejecting thrombolysis and other reasons without having intravenous thrombolysis from February 2012 to February 2014 were enrolled retrospectively. The control group was treated with conventional therapy and the thrombolytic group was treated with rt-PA (0. 9 mg/kg)intravenous thrombolytic therapy. The indicators including fibrinogen (Fib),coagulation function (prothrombin time [PT ]),activated partial thromboplastin time (APTT ), platelet (PLT ),high-sensitivity C-reactive protein (hs-CRP ),National Institute of Health Stroke Scale (NIHSS )scores,and activities of daily living scores (Barthel index)at before treatment and 24 h,7 and 14 days after treatment were observed respectively. The adverse events and complications were documented and compared with the control group. Results There were no significant differences in Fib,PT,APTT, PLT,hs-CRP,NIHSS score and Barthel index before treatment between the thrombolytic group and the con-trol group (all P>0. 05);at day 7 and 14 after treatment in the thrombolytic group,compared with before treatment,Fib (14 d after treatment),PLT,and hs-CRP were decreased,PT and APTT were prolonged,the NIHSS scores were decreased,and Barthel indexes were increased. There were significant differences (all P<0. 05). At day 14 after treatment,there were significant differences in Fib,PT,APTT,hs-CRP,NIHSS scores,and Barthel indexes (Fib:3. 25 ± 0. 38 g/L vs. 3. 55 ± 0. 28 g/L;PT:15. 7 ± 3. 2 s vs. 12. 9 ± 2. 5 s;APTT:42. 7 ± 3. 5 s vs. 38. 7 ± 2. 6 s;PLT:[189 ± 26]× 109/L vs. [201 ± 23]× 109/L;hs-CRP:5. 7 ± 0. 6 mg/L vs. 11. 3 ± 2. 2 mg/L;NIHSS scores:5. 6 ± 2. 4 vs. 9. 2 ± 4. 5;and Barthel indexes:68 ± 15 vs. 47 ± 5)between the two groups (all P <0. 05). Except 1 patient occurred symptomatic intracerebral hemorrhage after thrombolysis,no other serious complications were observed in the thrombolytic group. One patient in the control group had stress gastric ulcer and bleeding,no symptomatic intracerebral hemorrhage occurred. Conclusion Multimode CT guidance can be used as a reliable imaging evidence for patients with WUS expanding intravenous thrombolytic time window. Under the multimode CT guidance, using rt-PA for intravenous thrombolytic therapy has a certain efficacy.