Safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant chemotherapy combined with immunotherapy / 中华胃肠外科杂志

Objective: To investigate the safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy. Methods: Between November 2020 and April 2021, patients with locally advanced gastric cancer who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology were prospectively enrolled in this study. Inclusion criteria were: (1) patients who signed the informed consent form voluntarily before participating in the study; (2) age ranging from 18 to 75 years; (3) patients staged preoperatively as cT3-4N+M0 by the TNM staging system; (4) Eastern Collaborative Oncology Group score of 0-1; (5) estimated survival of more than 6 months, with the possibility of performing R0 resection for curative purposes; (6) sufficient organ and bone marrow function within 7 days before enrollment; and (7) complete gastric D2 radical surgery. Exclusion criteria were: (1) history of anti-PD-1 or PD-L1 antibody therapy and chemotherapy; (2) treatment with corticosteroids or other immunosuppre- ssants within 14 days before enrollment; (3) active period of autoimmune disease or interstitial pneumonia; (4) history of other malignant tumors; (5) surgery performed within 28 days before enrollment; and (6) allergy to the drug ingredients of the study. Follow-up was conducted by outpatient and telephone methods. During preoperative SOX chemotherapy combined with PD-1 inhibitor immunotherapy, follow-up was conducted every 3 weeks to understand the occurrence of adverse reactions of the patients; follow-up was conducted once after 1 month of surgical treatment to understand the adverse reactions and survival of patients. Observation indicators were: (1) condition of enrolled patients; (2) reassessment after preoperative therapy and operation received (3) postoperative conditions and pathological results. Evaluation criteria were: (1) tumor staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system; (2) tumor regression grading (TRG) of pathological results were evaluated with reference to AJCC standards; (3) treatment-related adverse reactions were evaluated according to version 5.0 of the Common Terminology Criteria for Adverse Events; (4) tumor response was evaluated by CT before and after treatment with RECIST V1.1 criteria; and (5) Clavien-Dindo complication grading system was used for postoperative complications assessment. Results: A total of 30 eligible patients were included. There were 25 males and 5 females with a median age of 60.5 (35-74) years. The primary tumor was located in the gastroesophageal junction in 12 cases, in the upper stomach in 8, in the middle stomach in 7, and in the lower stomach in 3. The preoperative clinical stage of 30 cases was III. Twenty-one patients experienced adverse reactions during neoadjuvant chemotherapy combined with immunotherapy, including four cases of CTCAE grade 3-4 adverse reactions resulting in bone marrow suppression and thoracic aortic thrombosis. All cases of adverse reactions were alleviated or disappeared after active symptomatic treatment. Among the 30 patients who underwent surgery, the time from chemotherapy combined with immunotherapy to surgery was 28 (23-49) days. All 30 patients underwent laparoscopic radical gastrectomy, of which 20 patients underwent laparoscopic-assisted radical gastric cancer resection; 10 patients underwent total gastrectomy for gastric cancer, combined with splenectomy in 1 case and cholecystectomy in 1 case. The surgery time was (239.9±67.0) min, intraoperative blood loss was 84 (10-400) ml, and the length of the incision was 7 (3-12) cm. The degree of adenocarcinoma was poorly differentiated in 18 cases, moderately differentiated in 12 cases, nerve invasion in 11 cases, and vascular invasion in 6 cases. The number lymph nodes that underwent dissection was 30 (17-58). The first of gas passage, the first postoperative defecation time, the postoperative liquid diet time, and the postoperative hospitalization time of 30 patients was 3 (2-6) d, 3 (2-13) d, 5 (3-12) d, and 10 (7-27) d, respectively. Postoperative complications occurred in 23 of 30 patients, including 7 cases of complications of Clavien-Dindo grade IIIa or above. Six patients improved after treatment and were discharged from hospital, while 1 patient died 27 days after surgery due to granulocyte deficiency, anemia, bilateral lung infection, and respiratory distress syndrome. The remaining 29 patients had no surgery-related morbidity or mortality within 30 days of discharge. Postoperative pathological examination showed TRG grades 0, 1, 2, and 3 in 8, 9, 4, and 9 cases, respectively, and the number of postoperative pathological TNM stages 0, I, II, and III was 8, 7, 8, and 7 cases, respectively. The pCR rate was 25.0% (8/32). Conclusion: Laparoscopic surgery after neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy for locally advanced gastric cancer is safe and feasible, with satisfactory short-term efficacy. Early detection and timely treatment of related complications are important.

Quantifying the duration of the preclinical detectable phase in cancer screening: a systematic review / 한국역학회지

OBJECTIVES@#The aim of this study was to provide an overview of published mathematical estimation approaches to quantify the duration of the preclinical detectable phase (PCDP) using data from cancer screening programs. @*METHODS@#A systematic search of PubMed and Embase was conducted for original studies presenting mathematical approaches using screening data. The studies were categorized by mathematical approach, data source, and assumptions made. Furthermore, estimates of the duration of the PCDP of breast and colorectal cancer were reported per study population. @*RESULTS@#From 689 publications, 34 estimation methods were included. Five distinct types of mathematical estimation approaches were identified: prevalence-to-incidence ratio (n=8), maximum likelihood estimation (n=16), expectation-maximization algorithm (n=1), regression of observed on expected (n=6) and Bayesian Markov-chain Monte Carlo estimation (n=5). Fourteen studies used data from both screened and unscreened populations, whereas 19 studies included only information from a screened population. Estimates of the duration of the PCDP varied between 2 years and 7 years for breast cancer in the Health Insurance Plan study (annual mammography and clinical breast examinations in women aged 40-64 years) and 2 years and 5 years for colorectal cancer in the Calvados study (a guaiac fecal occult blood test in men and women aged 45-74 years). @*CONCLUSIONS@#Different types of mathematical approaches lead to different estimates of the PCDP duration. We advise researchers to use the method that matches the data available, and to use multiple methods for estimation when possible, since no method is perfect.

Study on the association between occupational noise exposure and cardiovascular diseases / 中华劳动卫生职业病杂志

Occupational noise is one of the most common occupational hazards in the workplace. Long-term exposure to occupational noise could not only lead to the damage of the hearing system, but also may cause a certain impact on the cardiovascular system. Studies have shown that occupational noise exposure was positively associated with cardiovascular diseases, including hypertension, coronary heart disease and myocardial infarction. However, the results of studies on occupational noise exposure and stroke are still controversial. This paper reviews the relationship between occupational noise exposure and hypertension, coronary heart disease, stroke, myocardial infarction by summarizing the epidemiological data of domestic and foreign population in recent years. Our study could provide evidence for the design and implementation of well-designed epidemiological and mechanism studies, and the recognition of the role of occupational noise exposure in the occurrence and development of cardiovascular diseases, so as to better protect workers' health.

Application of computed tomography and magnetic resonance imaging fusion images for delineating gross tumor volume in three-dimensional conformal radiotherapy of nasopharyngeal carcinoma

Background: To evaluate computed tomography [CT] and magnetic resonance imaging [MRI] fusion images for delineating gross tumor volume [GTV] in three-dimensional conformal radiotherapy [3D-CRT] of nasophanrygeal carcinoma [NPC], and compare treatment outcomes between CT- and CT+MRI-based targets

Materials and Methods: A total of 120 NPC patients treated with 3D-CRT were included, in which, 60 each were treated with CT-based and 60 with CT+MRI fusion targets. We explored the clinical application of CT+MRI fusion targets and compared the 1-, 3-, and 5-year survival and relapse rates between both targets

Results: The clinical characteristics and treatment factors were well balanced. The differences in public volume using CT alone in the CT+MRI [Group A] and the CT arm [Group B] were not significant [33.6+/-2.18 vs. 34.3+/-2.98, P > 0.05]. The public volumes of GTV in the two arms were 49.48+/-2.46 cm[3] and 33.6+/-2.18 cm[3] respectively [P < 0.05]. CT+MR fusion images did not influence the one-, three-, and 5-year survival rates [100% vs. 98.3%, 85.0% vs. 81.2%, and 73.3% vs. 68.3%, respectively]. The three- and 5-year out-of-field progression was reduced in the CT+MRI arm. However, only the difference in 3-year out-of-field relapse rate was significant [3.3% vs. 13.3%; P < 0.05]. The incidence of acute toxicities was similar between groups

Conclusion: The variability in GTV delineation in NPC was ascribed to intermodality and not interobserver variability. CT+MR fusion images likely reduced the 3-year out-of-field relapse rate

Predictive values of TNF-alpha, IL-6, IL-10 for radiation Pneumonitis

Background: To investigate the expression of TNF-alpha, IL-6, IL-10 in the plasma of patients with lung cancer who received radiation therapy [RT], and to analyze the correlation between these cytokines and radiation pneumonitis [RP]. Materials and Methods: Patients with lung cancer who received 3D-CRT in our hospital were prospectively evaluated. Circulating cytokine levels were measured with ELISA before RT and at the end of RT. Regular follow-up was undertaken 3 months after RT. Statistical analysis was applied to determine the relevance of cytokines to radiation-induced lung injury. Results: Of 104 patients, 29 [27.9%] developed RP. The levels of TNF-alpha and IL-6 levels in the plasma after RT were significantly higher than before RT [p<0.05], whereas IL -10 levels were significantly lower after RT than before RT [p<0.05]. Before RT, TNF-alpha levels were higher in RP group [p<0.05],but there were no differences in TNF-alpha levels after RT. No association was observed between IL-6 and IL-10 levels and the risk of RP. Univariate analysis showed that baseline pulmonary function, smoking history, histopathology, lung volume receiving >/=20 Gy [V20], Mean lung dose [MLD] and total radiation dose were related to RP, but only MLD was an independent risk factor for RP in lung cancer patients [OR>1]. Conclusion: TNF-alpha levels in plasma were closely related to RP but still cannot be used as predictors for RP

Efficacy of pyrimethamine/sulfadoxine versus chloroquine for the treatment of uncomplicated falciparum malaria in children aged under 5 years

The children aged under 5 years from vast African areas badly suffer from falciparum malaria and many of them die of this disease. Therapeutic efficacy of anti-malaria drugs, especially pyrimethamine-sulfadoxine [PS] and chloroquine [CQ] to falciparum malaria is frequently evaluated and reported in recent 10 years. Unfortunately, to date, these widespread materials and researches have not been systematically collected and analyzed. In our study, two investigators were employed to widely and independently gather researches on efficacy of PS vs. CQ mono-therapy of falciparum malaria in children aged below 5 years in unpublished and published databases. Meta-analyses were conducted in categories of PS group and CQ group respectively. Pooled OR of PS vs. CQ was 0.11 [95%CI, 0.05-0.24]. PS showed higher therapeutic efficacy to falciparum malaria in less-than-5-year children than CQ. Random model was chosen to analyze for the heterogeneity existence between different studies. Subgroup analyses were performed, but heterogeneity was still presented. Heterogeneity might be caused by different resistance of falciparum malaria to PS and CQ in different settings. Malaria type associated with parasite species, basic information of PS and CQ, and PS and CQ resistant malaria control measures were demonstrated and discussed respectively in detail in this article

Current approaches to assess QTc prolongation for small molecule drug development / 中国药理学与毒理学杂志

Assessment of QTc prolongation is a critical step for small molecule drug development.ICH S7B continues to be the main frame to guide the assessment for this potential cardiovascular risk.The ICH guideline outlines a 3-step approach to QTc prolongation,including in vitro bERG inhibition,ex vivo action potential duration (APD),and in vivo animal telemetry approch.Dog,monkey,swine,rabbit,ferret,and guinea pig are the common laboratory animals used for in vivo electrophysiology studies,especially using conscious Beagle Dog. In addition to all these guideline standard studies,many newly developed approaches,such as receptor binding for hERG inhibition,ex vivo methods such as perfused rabbit heart or guinea pig heartare are useful models for this purpose.All these methods display good correlation to clinic outcomes,and are low cost and have rapid turn-around time in nature; so that,they can help rapidly and predict this potential cardiac liability,resulting into accelerating process for small molecule drug candidate development.

Biodegradation of cypermethrin by a newly isolated actinomycetes HU-S-01 from wastewater sludge

A new cypermethrin degrading strain was isolated from wastewater sludge using enrichment technique. On the basis of morphological, physiological, biochemical characteristics tests and 16S rDNA sequence analysis, the strain was determined to be a Streptomyces species, probably a strain of Streptomyces parvulus, so it was designated as Streptomyces sp. HU-S-01. The strain Streptomyces sp.HU-S-01 is aerobic and optimum growth temperature for the strain was found to be 26-28°C with initial pH range 6.0-9.0 and pH 7.5 was found to be the optimum. This strain can also completely degrade 3-phenoxybenzoic acid within 96 h at the concentration of 50 mg/L. The kinetic constants Vmax, Km, Kcat and Kcat/ Km of enzyme for cypermethrin were 1.236 micro mol/min, 6.418 micro mol/mL, 13.493 min and 2.102 mL/mol.min, respectively. The degradation products of cypermethrin were identified using gas chromatograph-mass spectrometric [GC-MS] analysis. The degradation pathway followed by HU-S-01 involves oxidative as well as hydrolyzing. Biodegradation ability of strain Streptomyces sp. HU-S-01 without toxic byproducts reveals its potential for further study as a biological agent for the remediation of soil, water or crops, contaminated with cypermethrin

Hybrid anaerobic baffled reactor for treatment of desizing wastewater

Polyvinyl alcohol-containing desizing wastewater discharged within final textile wastewater has a great impact to the environment due to its poor biodegradability. An improved lab-scale hybrid anaerobic baffled reactor was developed to treat desizing wastewater. The modification was achieved by increasing the height of hybrid anaerobic baffled reactor and application of proper effluent recycle enabled to increase the ability of entrapping microbe-rich small particles in the reactor and prompted the formation of granules. The significant difficulty in hybrid anaerobic baffled reactor operation is the slow start-up procedure, which is crucial to the overall polyvinyl alcohol-containing desizing wastewater treatment. Therefore, the ability of a hybrid anaerobic baffled reactor, treating desizing wastewater, to achieve a prompt start-up was studied at lab-scale. Results showed that inoculated with anaerobic granular sludge and adoption of effluent recycle during start-up, the system demonstrated a good performance of polyvinyl alcohol removal efficiency [above 17.2%] and satisfactory stability of pH and alkalinity in effluent [range around 7.4-8.0 and 700-920 mg/L, respectively] and the sludge appeared obviously granulation. Thus, the prompt start-up was achieved after 60 days. The start-up strategy used for this process has achieved its goals by creating an active microbial population. The improved lab-scale hybrid anaerobic baffled reactor proved to be an efficient reactor configuration for the treatment of desizing wastewater, which favored the prompt start-up of hybrid anaerobic baffled reactor. The results also provide evidence to modify the design of anaerobic baffled reactor to improve reactor performance

Development of the systematic object event data model for integrated point source pollution management

Previous works on database integration focused mainly on the creation of transformation interfaces between incompatible databases built up by different departments of the Taiwan Environmental Protection Administration, ignoring the demands of systematically and flexibly integrated information for advanced pollution control of point sources. To provide a systematic framework for flexible integration of distributed data, this paper presents a general model as the systematic object event data model based on systems thinking, to improve the integration capability of databases. The conceptual database framework for integrated pollution control was proposed as a result of the application of the systematic object event data model. The fundamental part of the systematic object event data model, creation of the object registry database, was put into practice from the year 2008. The object database of pollution source is available to factories in 2009, which helps factories to create and Taiwan environmental protection administration to maintain the consistent object data through the electronic application processes of permits. To construct various event databases that systematically connect to object database would be the following step to more efficiently provide systematic information from systematic data integration

Genetics of schizophrenia spectrum disorders: looking back and peering ahead

The genetics of schizophrenia spectrum disorders have come a long way since the early demonstration of a substantial genetic component by family, twin and adoption studies. After over a decade of intensive molecular genetic studies, initially by linkage scans and candidate gene association studies, and more recently genome-wide association studies, a picture is now emerging that susceptibility to schizophrenia spectrum disorders is determined by many genetic variants of different types, ranging from single nucleotide polymorphisms to copy number variants, including rare and de novo variants, of pleiotropic effects on multiple diagnoses and traits. Further large-scale genome-wide association studies, and the forthcoming availability of affordable whole-genome sequencing technology, will further characterise the genetic variants involved, which in turn will be translated to improved clinical practice.

Concomitant coronary artery disease among Asian ischaemic stroke patients

<p><b>INTRODUCTION</b>Coronary artery disease (CAD) is the leading cause of death following ischaemic stroke. We aimed to study the prevalence and associations of concomitant CAD among ischaemic stroke patients in Singapore.</p><p><b>MATERIALS AND METHODS</b>We prospectively studied 2686 consecutive Asian ischaemic stroke patients.</p><p><b>RESULTS</b>CAD was prevalent among 24% of the study patients. Older age, hypertension, diabetes, hyperlipidaemia, atrial fibrillation, large stroke and South Asian ethnicity were independently associated with CAD.</p><p><b>CONCLUSIONS</b>The variables found to be associated with CAD are known atherosclerotic risk factors (older age, hypertension, diabetes, hyperlipidaemia) or associations of cardioembolic stroke (atrial fibrillation, large stroke). The over-representation of South Asians with concomitant CAD is consistent with the high burden of CAD in this ethnic group.</p>

Timing of hospital presentation after acute cerebral infarction and patients' acceptance of intravenous thrombolysis

<p><b>INTRODUCTION</b>Intravenous thrombolysis has been shown to improve outcome after acute cerebral infarction if given within 3 hours of symptom onset. There are no data in Singapore on the timing of hospital presentation after acute cerebral infarction as well as factors and reasons for delayed presentation.</p><p><b>MATERIALS AND METHODS</b>As intravenous thrombolysis has recently been licensed for use in acute cerebral infarction in Singapore, we studied 100 consecutive acute cerebral infarction admitted to the Singapore General Hospital for timing of hospital presentation, reasons associated with delay in presentation and hypothetical acceptance of intravenous thrombolysis.</p><p><b>RESULTS</b>Only 9% of patients presented to hospital within 2 hours of symptom onset. Factors associated with hospital presentation within 2 hours were a large stroke and lack of pre-hospital consultation. Failure to recognise the severity of symptoms and inability to seek medical attention unaided were the 2 most common reasons for delayed presentation. One-third of patients or their relatives hypothetically would accept intravenous thrombolysis, suggesting that a thrombolysis service is feasible at the Singapore General Hospital. However, it would be hindered by the low proportion of patients who present early to hospital after symptom onset.</p><p><b>CONCLUSION</b>Our results support the need for a public education programme to highlight the identification of stroke symptoms and the need to present to hospital as soon as possible after the onset of stroke symptoms.</p>

A review on the clinical implementation of respiratorygated radiation therapy

Respiratory-gated treatment techniques have been introduced into the radiation oncology practice to manage target or organ motions. This paper will review the implementation of this type of gated treatment technique where the respiratory cycle is determined using an external marker. The external marker device is placed on the abdominal region between the xyphoid process and the umbilicus of the patient. An infrared camera tracks the motion of the marker to generate a surrogate for the respiratory cycle. The relationship, if any, between the respiratory cycle and the movement of the target can be complex. The four-dimensional computed tomography (4DCT) scanner is used to identify this motion for those patients that meet three requirements for the successful implementation of respiratory-gated treatment technique for radiation therapy. These requirements are (a) the respiratory cycle must be periodic and maintained during treatment, (b) the movement of the target must be related to the respiratory cycle, and (c) the gating window can be set sufficiently large to minimise the overall treatment time or increase the duty cycle and yet small enough to be within the gate. If the respiratory-gated treatment technique is employed, the end-expiration image set is typically used for treatment planning purposes because this image set represents the phase of the respiratory cycle where the anatomical movement is often the least for the longest time. Contouring should account for tumour residual motion, setup uncertainty, and also allow for deviation from the expected respiratory cycle during treatment. Respiratory-gated intensity-modulated radiation therapy (IMRT) treatment plans must also be validated prior to treatment. Quality assurance should be performed to check for positional changes and the output in association with the motion-gated technique. To avoid potential treatment errors, radiation therapist (radiographer) should be regularly in-serviced and made aware of the need to invoke the gating feature when prescribed for selected patients.

Non-Clinical Studies of Botanical Medicines as New Drugs-U.S. Regulatory Perspectives / 日本東洋医学雑誌

To encourage development of new drugs from botanical sources, the U. S Food and Drug Administration (FDA) has published a draft Guidance for Industry: Botanical Drug Products (www.fda.gov/cder/guidance/1221.dft.pdf) in August of 2000.<br>The Guidance stipulates that for herbal preparations with substantial marketing history, past human experiences may be taken into consideration for safety assessment. In contrast with development of pure chemical drugs, clinical studies on herbal medicines can thus be initialed with less extensive lesting of non-clinical toxicity. However, most of the historical human experlences are not well documentad and often of poor quality data. In such cases, animal toxicity and toxicology studies may still be required for many botanical preparations, especially to support large scale or long term clinical trials. In this presentation, conventional non-clinical requirements for approval of pure chemical drugs will be reviewed briefly and how such requirements may be modified in scale/timing and applied to the development of botanical new drugs will be discussed.