[From treatment to whole course management: envisioning comprehensive management of Talaromycosis marneffei].

Talaromycosis marneffei has been increasing in recent years. Our understanding of this disease has gradually deepened through extensive basic and clinical research, but there are still many limitations. In this article, by incorporating the latest research advancements, we discuss important issues in managing Talaromycosis marneffei trends, aiming to guide effective prevention and control of the disease, improving public health, and reducing the healthcare burden.

[Digitalization of perioperative traumatic stress in enhanced recovery after surgery program: current application and future prospect].

Perioperative traumatic stress is a systemic nonspecific response caused by stimuli such as anesthesia, surgery, pain and anxiety, which lasts throughout the perioperative period.The continuous excessive stress response is not conducive to the postoperative rehabilitation of patients. Enhanced recovery after surgery (ERAS), a research hotspot of modern surgery, can significantly reduce perioperative pain and stress, thus promoting the rehabilitation of patients. With the progress of artificial intelligence and information technology, wearable, non-invasive, real-time heart rate variability (HRV) dynamic monitoring can effectively realize the digitalization of stress monitoring with low price, which is worthy of clinical application. Therefore, the use of HRV for digital monitoring of perioperative stress has a significant research value. Moreover, the combination of HRV and ERAS has shown its advantages and the prospect of clinical application is worthy of anticipating.

[The discussion of related issues in the efficacy evaluation of COVID-19 vaccine].

The COVID-19 swept across the countries and regions all over the world in the past one year. The marketing of an effective and safe COVID-19 vaccine is expected to control the spread of the disease. A placebo-controlled field efficacy trial is generally considered in the pivotal study of COVID-19 vaccine to observe whether it is able to reduce the incidence rate of the disease effectively. This paper is to introduce and discuss the considerations in study design and the choice of endpoint, statistical evaluation methods, primary estimand choosing and the strategies to various intercurrent events in the COVID-19 efficacy trials.

[Clinical research of a continuous auscultation recorder based on artificial intelligence].

Objective: To investigate the feasibility and clinical significance of a continuous auscultation recorder of bowel sounds based on artificial intelligence in monitoring the bowel sounds. Methods: From November 1,2018 to August 12,2019, a continuous auscultation recorder of bowel sounds was applied to monitor the perioperative bowel sounds of 31 patients undergoing colorectal surgery, in order to discovery underlying rules which might be used to guide clinical practice. Results: After the operation, the bowel sounds continued to exist for (1.8±0.8) h, and then gradually weakened or disappeared, and recovered gradually after (11.2±3.5) h. The first exhaust and the first defecation were detected at the time of (22.7±5.8) h and (28.7±6.9) h after surgery, respectively. The bowel sounds rate increased after eating, and decreased significantly after exhaust/defecation. Conclusions: The continuous auscultation recorder of bowel sounds based on artificial intelligence was safe and effective, which can afford help to clinical evaluation.

[Diagnostic value of optical imaging combined with indocyanine green-guided sentinel lymph node biopsy in gastric cancer: a meta-analysis].

Objective: To systematically evaluate the diagnostic value of optical imaging combined with indocyanine green (ICG)-guided sentinel lymph node (SLN) biopsy in gastric cancer, and to identify potential factors that would influence diagnostic accuracy. Methods: Study was carried out by searching the electronic database of PubMed, Embase, Medline, Web of Science, and the Cochrane Library with keywords as "gastric/stomach" and "cancer/carcinoma/tumor/tumour/adenocarcinoma/neoplasm" and "sentinel lymph node" and "near-infrared/NIR or fluorescent imaging" and "indocyanine green/ICG" . Literature inclusion criteria: (1) gastric cancer clinical stage was cT0-3; (2) clinical stage determined by at least 2 kinds of imaging modalities; (3) optical imaging (near-infrared or fluorescence imaging) combined with ICG-guided SLN biopsy; (4) prospective study to predict lymph node metastasis; (5) intraoperative or postoperative pathology for all lymph nodes removed; (6) patients number in the literature >10 cases. Exclusion criteria: (1) patients with a history of ICG allergy or chemoradiotherapy; (2) previous history of endoscopic mucosal resection or endoscopic submucosal dissection; (3) patients with a variety of gastrointestinal tumor; (4) case reports, conference abstracts, clinical guidelines, editorials, reviews, meta-analysis and correspondence letters; (5) in vitro or animal experiments; (6) insufficient diagnostic efficacy data. The meta-analysis was performed in the Stata12.0 software using the "bivariate mixed-effects model" combined with the "midas" command to pool the data. Information such as true positive value, false positive value, false negative value, and true negative value of each included articles were extracted. The literature quality assessment map was drawn to describe the overall quality of the articles; the heterogeneity analysis was performed with the forest map, with P<0.01 considered as statistical significance; the funnel plot was used to describe publication bias, with P<0.1 considered as statistically significant. Area under curve (AUC) of summary receiver operator characteristic (SROC) was used to describe the diagnostic accuracy and the AUC closer to 1 indicated higher diagnostic accuracy. If there was heterogeneity (I(2)>50%) among studies, regression analysis and subgroup analysis were performed. P<0.05 was considered as statistically significant. Results: A total of 15 studies (1020 patients) were included. The optical imaging contained near-infrared (NIR) and fluorescent imaging (FI). The diagnostic value of optical imaging combined with ICG-guided SLN biopsy in gastric cancer was as follows: the pooled sensitivity (Sen) was 0.95 (95% CI: 0.82 to 0.99), specificity (Spe) was 1.00 (95% CI: 0.92 to 1.00), positive likelihood ratio (PLR) was 30.39 (95% CI: 9.14 to 101.06), negative likelihood ratio (NLR) was 0.05 (95% CI:0.01 to 0.20), diagnostic odds ratio (DOR) was 225.54 (95% CI: 88.81 to 572.77), AUC was 1.00 (95% CI: 0.99 to 1.00), threshold value was sensitivity=0.95 (95% CI: 0.82 to 0.99) and specificity=1.00 (95% CI: 0.92 to 1.00). Deeks method revealed DOR funnel plot of SLN biopsy was not asymmetrical obviously with significant difference (P=0.01), which indicated remarkable publishing bias. Meta-subgroup analysis showed that compared to FI, NIR imaging had higher sensitivity (0.98 vs. 0.73); compared to 0 minutes, optical imaging performed 20 minutes after ICG injection had higher sensitivity (0.98 vs. 0.70); compared to mean detected number of SLN of 4, mean detected number≥4 had higher sensitivity (0.96 vs. 0.68); compared to HE stain, immunohistochemistry + HE had higher sensitivity (0.99 vs. 0.84); compared to subserous injection of ICG, submucosa injection of ICG had higher sensitivity (0.98 vs. 0.40); compared to injection of 5 g/L ICG, 0.5 g/L and 0.05 g/L had higher sensitivity (0.98 vs. 0.83); compared to cT2-3 tumor, early stage (cT1) tumor had higher sensitivity (0.96 vs. 0.72); compared to ≤ enrolled 26 cases in the study, > 26 cases had higher sensitivity (0.96 vs. 0.65); compared to papers before 2010, papers after 2010 had higher sensitivity (0.97 vs. 0.81); whose differences were all significant. Sensitivity differences between mean tumor diameter of ≤30 cm and >30 cm, open surgery and laparoscopic surgery, lymph node regional dissection and retrieved dissection were not significant (all P>0.05). Conclusions: Optical imaging combined with ICG-guided SLN biopsy is clinically feasible, and especially suitable for early gastric cancer. However, the ICG being used in current studies may be overdosed. Higher sensitivity may be achieved from NIR imaging when compared with FI method.

[Analysis of differences in epidemiology and clinical features of Guillain-Barré syndrome between rural and urban areas of southern China].

Objective: To explore the differences in epidemiology and clinical features of Guillain- Barré syndrome (GBS) between rural and urban areas of southern China. Methods: The clinical data of 759 hospitalized GBS patients from 31 hospitals of 13 provinces/cities in southern China, between January 1st, 2013 and September 30th, 2016, were collected and analyzed retrospectively. Results: The risk of GBS was higher for males than females in rural and urban areas and the median age was 49 and 48 years, respectively. Seasonal clustering in winter and spring was noted in both rural and urban areas, and the seasonal trend was more markedly in rural areas, but the differences showed no statistical significance. There were 70.37% of patients in rural areas and 73.69% in urban areas who had antecedent respiratory infection. The median time from onset to nadir was 7 days, and Hughes Disability Scale at admission, nadir and discharge were (2.95±1.10 vs 2.84±1.15), (3.25±1.11 vs 3.14±1.21), (2.02±1.24 vs 2.00±1.31) in rural and urban areas respectively. Albuminocytologic dissociation was present in 84.34% of patients in rural areas and 84.62% of cases in urban areas. There were 8.65% and 10.94% of cases in rural and urban areas who required mechanical ventilation during hospitalization, respectively. Demyelinating GBS accounted for 53.29% and 48.77%, respectively, in patients with findings of nerve conduction studies available in rural and urban areas. Conclusions: GBS in rural areas of southern China showed male predominance and a peak of spring and winter occurrence, with respiratory infection as the predominated preceding events and demyelinating GBS being main clinical subtype. Winter and spring showed a higher incidence of GBS in rural and urban areas. There were no significant differences of sex, age, preceding events, season trend, progression of disease, clinical subtypes and cerebrospinal fluid investigations in GBS patients between rural and urban areas.

[Association between body mass index and its change and type 2 diabetes mellitus risk in a prospective study].

Objective: To investigate the influence of body mass index (BMI) and its change on the incidence of type 2 diabetes mellitus (T2DM) in an adult cohort. Methods: A total of 3 043 subjects randomly selected among those without T2DM at baseline survey from the Rural Deqing Health Cohort Study were included into this study and follow up was conducted for 1 867 of them from July to November 2015. The subjects were divided into 3 groups according to their baseline BMI, normal group (BMI<24.0), overweight group (BMI: 24.0-27.9) and obese group (BMI≥28.0) and the subjects with stable weight (BMI change of-0.05 to + 0.05 per year) were used as the referent category. Cox proportional model was used to estimate associations between BMI, its changes and T2DM. Results: With an average of (8.68±1.25) person years, 213 new T2DM cases, including 125 females were detected, and incidence density was 13.14 per 1 000 person years. After adjusted for other covariates, the risk for incidence of T2DM was significantly higher in subjects with baseline BMI≥28.0 kg/m2 than those with baseline BMI<24.0 kg/m2 (aHR=2.12, 95% CI: 1.22-3.68), and weight gains were strongly associated with the incidence of T2DM in those with baseline BMI< 24.0 kg/m2 (aHR=2.21, 95%CI:1.17-4.17). Conclusion: Both BMI and its change were significantly associated with incidence of T2DM, especially in the population with BMI<24.0 kg/m2 at baseline.

Diagnostic performance of dual-source CT coronary angiography with and without heart rate control: systematic review and meta-analysis.

AIM: To investigate the diagnostic accuracy of dual-source computed tomography (DSCT) coronary angiography with and without the application of a ß-blocker. MATERIALS AND METHODS: An exact binomial rendition of the bivariate mixed-effects regression model was used to synthesize diagnostic test data. RESULTS: The pooled sensitivity at the patient level was 0.98 [95% confidence intervals (CI): 0.97-0.99], and specificity 0.88 (95% CI: 0.84-0.91). The results showed that without heart rate control, the sensitivity and specificity at the patient level did not decrease (p = 0.27 and 0.56, respectively). At the artery level, no significant differences in sensitivity and specificity for studies with and without heart rate control were detected (p = 0.04 and 0.05, respectively). At the segment level, the specificity decreased without heart rate control (p = 0.03), whereas the sensitivity was not influenced (p = 0.63). The median radiation exposure was 2.6 mSv, with 1.6 mSv and 8 mSv for heart rate-controlled studies and uncontrolled studies, respectively. CONCLUSIONS: DSCT coronary angiography without heart rate control has a similar excellent diagnostic performance at the patient level as that of heart rate control groups. However, controlling for heart rate to decrease radiation and to provide effective information for selecting the therapeutic strategy and risk stratification is recommended.

Aspisol inhibits tumor growth and induces apoptosis in breast cancer.

UNLABELLED: Nonsteroidal anti-inflammatory drugs inhibit cell proliferation and induce apoptosis in various cancer cell lines, which is considered to be an important mechanism for their anti-tumor activity and cancer prevention. However, the molecular mechanisms through which these compounds induce apoptosis are not well understood. AIM: to determine the effects of nonselective cyclooxygenase-2 (COX-2) inhibitor, aspisol on breast cancer cells in vitro and in vivo. METHODS: The cytotoxic activity of aspisol was evaluated by MTT assay. The apoptosis index of cells was measured by flow cytometry. Immunohistochemical staining was used to detect expressions of COX-2 and caspase-3 in MDA-MB-231 cells. The expression of bcl-2 and bax was analyzed by Western blot analysis. The content of prostaglandin E2 (PGE2) in MDA-MB-231 cells was estimated by ELISA. In vivo apoptosis of the tumor cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). RESULTS: Our results showed that aspisol reduced viability of MDA-MB-231 cells in time- and dose- dependent fashions and induced apoptosis by increase of caspase-3 and bax expressions while decrease of COX-2 and bcl-2 expression in vitro. In addition, exposure to aspisol decreased the basal release of PGE2. In vivo, aspisol also inhibited the proliferation of breast cancer cells and induced their apoptosis. CONCLUSIONS: Our in vitro and in vivo data indicated that the antitumor effects of aspisol on breast cancer cells was probably mediated by the induction of apoptosis, and it could be linked to the downregulation of the COX-2 or bcl-2 expression and up-regulation of caspase-3 or bax expression.

D-lactic acidosis secondary to short bowel syndrome.

A 12 year old boy presented with 11 episodes of weakness, ataxia, nausea, slurred speech, dehydration, and sometimes severe lethargy bordering on coma. A year previously the boy had small intestinal resections leaving 20 cm of small bowel remaining. D-lactic acidosis was diagnosed on the basis of a D-lactate level of 5.23 mmol/l. The clinical presentation of the disease is recurrent episodes of unusual neurological manifestations and severe metabolic acidosis. The diagnosis is dependent on the presentations and the plasma D-lactate level. Development of the syndrome seems to be the effect of the accumulation of D-lactic acid.

Dicyclomine, an M1 muscarinic antagonist, reduces infarct volume in a rat subdural hematoma model.

The rat subdural hematoma (SDH) model produces a zone of ischemic brain damage within the hemisphere beneath the SDH. Previous studies have measured large increases in extracellular acetylcholine during cerebral ischemia in the rat. We examined infarct volume after selectively blocking muscarinic M1 receptors with dicyclomine during SDH. Rats were anesthetized with isoflurane (2%), intubated, and femoral artery and vein cannulated. Autologous blood (0.375 ml) was injected (0.05 ml/min) under the dura of the right parietal cortex. Dicyclomine (5 mg/kg, i.v.) was injected at 5 min after and again at 2 h after completion of the subdural blood infusion. Blood pressure and intracranial pressure (ICP) were continuously measured. At 4 h after SDH rats were euthanized, brains sectioned, and immunoreacted with glia fibrillary acidic protein. Cortical infarct volume was quantified in coronal brain sections at 0.7-mm intervals from +1.0 mm to -3.9 mm relative to bregma. Infarct volume in drug-treated rats (n = 10) 22.1 +/- 6.99 mm3 was significantly smaller (p < 0.02) than vehicle treated rats (n = 10) 56.7 +/- 9.59 mm3. ICP, blood pressure and cerebral perfusion pressure were not significantly different between groups. These data suggest that activation of M1 muscarinic receptors during an ischemic event may contribute to the development of subsequent pathology.

Genetic aberration in primary hepatocellular carcinoma: correlation between p53 gene mutation and loss-of-heterozygosity on chromosome 16q21-q23 and 9p21-p23.

To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65%), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49%) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24%) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/p16 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21-q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC.

Artificial SMA valve for treatment of urinary incontinence: upgrading of valve and introduction of transcutaneous transformer.

This paper is concerned with the development of an artificial urethral valve driven by shape memory alloy actuators, which is attached onto the urethra of a urinary incontinence sufferer for treating the involuntary micturition. Three types of compact cylindrical valves are assembled and their opening and closing functions are examined experimentally. The updated valve is heated and opened by using the transcutaneous energy transformer consisting of a pair of flexible spiral-formed copper wire coils. The experiment using the canine urinary canal verifies that the total system of the valve and the transformer works well as an artificial sphictor muscle and controls the urinary flow through the canal appropriately.

Recovery of allografted small intestine function.

AIM: To investigate recovery of the allografted small intestine function after clinical small bowel transplantation (SBT). METHODS: The structure of the graft was evaluated by endoscopic biopsy and histopathologic examination. Graft functions were assessed by D-xylose absorption, barium studies, nitrogen balance calculation, and blood and stool cultures. Nutritional status of the recipients was judged by measurement of body weight and serum protein concentrations. RESULTS: The recipient discontinued total parenteral nutrition (TPN) and resumed oral nutrition 100 d after SBT. On oral diet, the patient maintained a normal nutritional status, gained weight by 3 kg, and had a normal serum albumin concentration (40.2 g/L ± 0.2 g/L). Satisfactory D-xylose absorption was achieved 8 wk after the operation. Nitrogen balance of the gut was maintained well and increased gradually. Serial mucosal biopsy showed normal structures 2 wk after grafting, without evidence of rejection and graft versus host diseases (GVHD). Barium studies conducted on the 10(th) day and 38(th) day by barium studies revealed that the grafted small bowel motility showed normal patterns of peristalsis and transit. No bacterial translocations were noted. CONCLUSION: Function of the grafted small intestine recovered satisfactorily 100 d after transplantation, indicating good clinical outcome of SBT.

Endoscopic monitoring in small bowel transplantation.

AIM: To investigate the role of endoscopic monitoring in small bowel transplantation. METHODS: This study was conducted in two parts-an initial experimental study followed by a clinical study. In the experimental study, segmental small bowel allotransplantation was performed on white outbred pigs. Stomas were created for exteriorization of the proximal and distal ends of the intestines (Thiry-Vella loop). The grafts were monitored by endoscopy via stomas, with or without immunosuppressive therapy. For the clinical study, the whole small-bowel allograft of a woman with short bowel syndrome was endoscopically monitored via distal stoma. RESULTS: The most common endoscopic findings of graft rejection following small bowel allotransplantation were mucosal erythema, erosion, and ulceration. Diffuse ulceration with bleeding occurred in the late phase of rejection. CONCLUSION: Endoscopic monitoring is essential to small bowel transplantation.

Neocarzinostatin-mediated DNA damage in a model AGT.ACT site: mechanistic studies of thiol-sensitive partitioning of C4' DNA damage products.

Double-strand (DS) DNA damage caused by neocarzinostatin (NCS) has been studied in the trinucleotide AGT-ACT sequence in an AP-1 transcription factor binding site. There are strong similarities between bistranded lesions produced at AGT.ACT and AGC-GCT, including the fact that DS lesions outnumber SS lesions on the AGT and AGC strands, while SS exceed DS on the ACT and GCT strands. Structure-function studies revealed that a variety of different thiols produced bistranded lesions in this model by predominantly C4'-hydrogen atom abstraction (84-93%) at the T of AGT and C5'-hydrogen atom abstraction (87-91%) at the T of ACT. Single-strand (SS) lesions were found to represent a variable mixture of C4' and C5' chemistry. The C4'-hydroxylated abasic site occurred in both SS and DS lesions at both sites and accounted for most of the DS damage at AGT (60-83%); the remaining damage consisted of 3'-phosphoglycolate- and 3'-phosphate-ended fragments. The nature of the thiol was found to affect the partitioning of the breakdown products arising from C4' and, to a lesser extent, C5' hydrogen atom abstraction. Production of 3'-phosphoglycolate residues, restricted mainly to the T of AGT in bistranded lesions, correlated with the incidence of direct DS breaks in the AGT.ACT model and in plasmid DNA and appeared to be influenced by the reducing power of the thiol activator. Furthermore, hydrazine and sodium borohydride both inhibited the formation of glycolate, an effect that was exploited to determine the rate constant for 3'-phosphoglycolate formation: 0.06 min-1 at 0 degree C, pH 7.4. Under anaerobic conditions, the nitroaromatic radiation sensitizer misonidazole caused a large increase in glycolate production in both SS and DS lesions formed by NCS, which suggests that the formation of 3'-phosphoglycolate, like 3'-formylphosphate generated by C5' chemistry, involves an oxyradical intermediate. The pathways for DNA damage involving C4' and C5' hydrogen atom abstraction thus share many common features, several of which are consistent with a mechanism for the production of NCS-mediated bistranded lesions at AGT.ACT that involves a tetraoxide bridge joining the lesions on opposite strands of DNA.

[The adverse effect of catheter ablation on the AV junction in experimental dogs].

The purpose of this study was to assess the adverse effects of catheter electrical ablation. Eighteen anesthetized mongrel dogs received 10-400 J of DC countershocks one to five times in each of them near the region of AVJ. Complete AV block was established, no pacemaker was implanted. Electrical unstability was seen nearly in all. Among the date of observation (1-547 days), 16 dogs died spontaneously and the other two were killed. Gross and microscopic examination revealed that cardiac damage produced by DC shock was diffusely spread over the endocardium/valve, myocardium and epicardial layers. The prominent lesions of the acute stage were myocytolysis and/or necrosis of myocardium/endocardium. In chronic stage, diffuse fibrosis and other types of tissue degeneration were revealed, some dogs had both acute and chronic lesions at the same time. Two dogs with perforated aortic valve revealed an elevation of PAEDP, one of them developed marked right heart failure and ascites. We proposed that the acute submicroscopic injury induced by DC shock may progress to a diffuse and irreversible pathologic changes. Therefore, the chronic adverse effects of catheter ablation should be evaluated carefully.