[Net survival analysis of cancer in Zhongshan City of Guangdong Province in China, 1970 to 2014].

Objective: To analyze survival data of cancer from 1970 to 2014 in Zhongshan City, Guangdong Province, and provide scientific basis for cancer prevention and control in Zhongshan City. Methods: The tumor incidence data of Zhongshan City, Guangdong Province from 1970 to 2014 were collected from Zhongshan Cancer Registry, and all patients were followed up to December 31, 2019. The standardized 5-year net survival rates and their annual percentage change (APC) and average annual percentage change (AAPC) for total and major cancers at different times were used to describe statistical analysis. The standardized survival rates were weighted using the International Cancer Survival Standard Age Coefficients. Results: There were 78 854 cancer patients eligible for the study in Zhongshan City of Guangdong Province from 1970 to 2014, among which lung cancer (13 466 cases, 17.08%), nasopharyngeal cancer (9715 cases, 12.32%) and liver cancer (9707 cases, 12.31%) were the main types of cancer. The morphology verification was 69.87% in the whole of cancers and the ranges were 21.07% to 97.00% in major cancers. From 2010 to 2014, the 5-year age-standardized net survival rates of cancers for all, males and females in Zhongshan City were 39.74%, 30.92% and 52.47%, in which were 97.98% for thyroid cancer, 74.29% for brain and central nervous system tumors, 73.92% for nasopharyngeal cancer, 50.23% for colorectal cancer, 81.38% for female breast cancer, 78.81% for uterine body cancer, 68.57% for cervical cancer, 49.33% for prostate cancer, 16.19% for lung cancer , 12.14% for liver cancer, and 11.78% for esophageal cancer, respectively. The survival rates of all cancers in Zhongshan City showed an increasing trends in 1970-2014 (AAPC=1.5%, P=0.025), and it was higher in female cancers than that of male in all periods. Conclusion: The standardized 5-year net survival rates of all and major cancers in Zhongshan City of Guangdong Province show an increasing trend from 1970 to 2014, but they are still at a medium-low levels compared with the countries and regions participating in CONCORD-3 project, suggesting that Zhongshan should continue to strengthen cancer prevention and control.

[Research advances on stem cell therapy for diabetic foot wounds].

Diabetic foot wound repair is a challenging issue in clinical practice. Due to the influence of multiple factors including the damage and regeneration failure of local tissue, the impaired pathways of wound repairing through blood vessels and nerve nutrition, and disorders of a variety of cellular factors, traditional treatment methods are often difficult to achieve good therapeutic effects. Stem cells are a type of cells with potentials of multidirectional differentiation, which also possess functions such as regulating immunity and paracrine to facilitate the comprehensive wound repair, so they have promising application prospect at present for the treatment of diabetic foot wounds. Because the relevant parameters of stem cell treatment are in the exploratory phase, there were no standardized data. This paper reviews the application of stem cells in the research of diabetic foot wound treatment over the past 6 years, analyzing and summarizing the contents in focused aspects including the types and sources of stem cells, effects of donor age and gender on stem cells, mode of administration, transplantation survival rate and safety, which may provide a reference for further application of stem cells in the clinical treatment of diabetic foot wound.

[Influence factors of poor efficacy after flap repair operation in patients with pressure ulcers].

Objective: To investigate the influence factors of poor efficacy after flap repair operation in patients with pressure ulcers. Methods: The retrospective case series study was conducted. From January 2011 to June 2021, 125 patients with stage Ⅲ and Ⅳ pressure ulcers treated in Hainan General Hospital met the inclusion criteria. There were 82 males and 43 females, aged 15-90 (57±20) years. According to the postoperative effects, the patients were divided into poor efficacy group (47 cases) and good efficacy group (78 cases). The clinical data of patients in the two groups were collected, including the age, gender, location, stage, size, and bone exposure of pressure ulcers, preoperative microorganism culture results of wound exudate sample, whether combined with osteomyelitis, diabetes, lower limb paroxysmal myospasm, and gatism or not, the number of surgical debridement combined with negative-pressure wound therapy, type of surgical flap, postoperative position, and preoperative albumin, leukocyte, C-reactive protein (CRP), and hemoglobin. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, and chi-square test. The binary multivariate logistic regression analysis was conducted to screen the independent risk factors influencing the poor efficacy after flap repair operation in 125 patients with stage Ⅲ and Ⅳ pressure ulcers. Results: The ratio of patients with lower limb paroxysmal myospasm in poor efficacy group was 22/47, which was significantly higher than 3/78 in good efficacy group (χ2=33.83, P<0.01). The preoperative hemoglobin level of patients in poor efficacy group was (102±17) g/L, which was significantly lower than (113±20) g/L in good efficacy group (t=-3.24, P<0.01). The preoperative CRP level of patients was 39.1 (14.1, 91.6) mg/L in poor efficacy group, which was significantly higher than 15.3 (6.6, 42.0) mg/L in good efficacy group (Z=-3.04, P<0.01). There were no statistically significant differences in other indexes between patients in the two groups (P>0.05). Multivariate logistic regression analysis showed that age, lower limb paroxysmal myospasm, and preoperative hemoglobin level were the independent risk factors for poor efficacy after flap repair operation in patients with pressure ulcers (with odds ratios of 1.03, 40.69, and 0.97, 95% confidence intervals of 1.00-1.06, 9.18-180.39, and 0.95-1.00, respectively, P<0.05 or P<0.01). Conclusions: Poor efficacy after flap repair operation in patients with pressure ulcers is affected by many factors, among which the age, lower limb paroxysmal myospasm, and preoperative hemoglobin level are the independent risk factors.

Effect of SOCS3 on lung injury in rats with severe acute pancreatitis through regulating JAK2/STAT3 signaling pathway.

OBJECTIVE: To explore the effect of suppressor of cytokine signaling 3 (SOCS3) on the lung injury in rats with severe acute pancreatitis (SAP) by regulating the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway. MATERIALS AND METHODS: Sprague-Dawley rats were divided into control group (n=20) and SAP model group (established via injection of 5% sodium taurocholate, n=40). Then, SOCS3 was overexpressed using the adenovirus in 20 rats in SAP model group. The serum amylase (AMY) was detected, whether the transfection was successful was verified via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), the hepatic function indexes were detected, the pathological changes were observed using hematoxylin-eosin (HE) staining, and the wet/dry weight ratio (W/D) was calculated. Moreover, the content of serum inflammatory factors was detected via enzyme-linked immunosorbent assay (ELISA) and the expression levels of JAK2/STAT3 signaling pathway genes and proteins were detected through RT-PCR and Western blotting. RESULTS: The content of AMY in SAP model group was significantly increased, indicating the successful modeling. SOCS3 was significantly increased in transfection group, suggesting that the transfection efficiency was significant. The content of alanine aminotransferase (ALT),  and aspartate aminotransferase (AST) in SOCS3 transfection group was significantly lower than in model group. According to the histopathological observation, there were lung injury, pulmonary edema, hemorrhage, severe inflammatory response, and alveolar congestion in SAP model group. There were almost no pathological changes in SOCS3 transfection group. In SOCS3 transfection group, the content of serum interleukin-6 (IL-6), IL-18 and tumor necrosis factor-α (TNF-α), the mRNA and protein expressions of IL-6, JAK2, and STAT3 were all remarkably declined. CONCLUSIONS: SOCS3 inhibits the activation of the JAK2/STAT3 pathway and the increase of inflammatory factors, promoting the repair of lung injury in SAP rats.

[Incidence and mortality of laryngeal cancer in China, 2014].

Objective: To estimate the incidence and mortality of laryngeal cancer in China based on the cancer registration data in 2014, collected by the National Central Cancer Registry (NCCR), and to provide support data for the control and prevention of laryngeal cancer. Methods: The incident and death data of laryngeal cancer in 2014 from 339 cancer registries met the quality criteria of NCCR, and then adopted for analysis. The incident and death number, crude rate, age standardized rate, truncated rate and proportion which stratified by areas (urban/rural) and age were calculated. The nationwide incidence and mortality of laryngeal cancer in 2014 were estimated by combining with those data on national population in 2014. Chinese population census in 2000 and Segi's population were used for age-standardized incidence/mortality rates. Results: It was estimates that 23.4 thousand new cases of laryngeal cancer occurred in China in 2014. There were 20.8 thousand males and 2.6 thousand females. And 14.5 thousand occurred in urban areas, while 8.9 thousand in rural areas. The age standardized rates of incidence by world standard population (ASRs world) in male, female and both genders were 2.05/100, 000, 0.24/100, 000 and 1.14/100, 000, respectively, whereas those were 1.22/100, 000 and 1.03/100, 000 for urban and rural areas. The incidence was much higher in males than females, and slightly higher in urban areas than those in rural areas. Moreover, it was estimates that 13.2 thousand death cases of laryngeal cancer occurred in China in 2014. There were 11.5 thousand males and 1.7 thousand females. And 7.8 thousand occurred in urban areas, while 5.4 thousand in rural areas. The age standardized rates of mortality by ASRs world in male, female and both genders were 1.08/100, 000, 0.14/100, 000 and 0.60/100, 000, respectively, whereas those were 0.60/100, 000 and 0.59/100, 000 for urban and rural areas. The mortality was much higher in males than females, and slightly higher in urban areas than those in rural areas. In males, the age specific incidence and mortality of laryngeal cancer increased greatly from 40-44 and 45-44 years old, respectively, and peaked at age group of 75-79 and >85 years old. In females, the age specific incidence and mortality increased slowly from 50-54 and 60-64 years old, respectively, and peaked at age group of 80-84 and >85 years old. The trends remained similar in urban and rural areas, except for the different peak ages. Conclusions: The incidence and mortality of laryngeal cancer in China are at middle-low levels worldwide, and there are obvious differences between urban and rural areas with distinct gender disparity. Comprehensive prevention and control strategies should be carried out according to local status and age groups.

Identification of sex-specific urinary biomarkers for major depressive disorder by combined application of NMR- and GC-MS-based metabonomics.

Women are more vulnerable to major depressive disorder (MDD) than men. However, molecular biomarkers of sex differences are limited. Here we combined gas chromatography-mass spectrometry (GC-MS)- and nuclear magnetic resonance (NMR)-based metabonomics to investigate sex differences of urinary metabolite markers in MDD, and further explore their potential of diagnosing MDD. Consequently, the metabolite signatures of women and men MDD subjects were significantly different from of that in their respective healthy controls (HCs). Twenty seven women and 36 men related differentially expressed metabolites were identified in MDD. Fourteen metabolites were changed in both women and men MDD subjects. Significantly, the women-specific (m-Hydroxyphenylacetate, malonate, glycolate, hypoxanthine, isobutyrate and azelaic acid) and men-specific (tyrosine, N-acetyl-d-glucosamine, N-methylnicotinamide, indoxyl sulfate, citrate and succinate) marker panels were further identified, which could differentiate men and women MDD patients from their respective HCs with higher accuracy than previously reported sex-nonspecific marker panels. Our findings demonstrate that men and women MDD patients have distinct metabonomic signatures and sex-specific biomarkers have promising values in diagnosing MDD.

Effect of continuous infusion of midazolam on immune function in pediatric patients after surgery.

The current study was performed to investigate the effects of midazolam on immune function in pediatric patients after surgery and possible mechanism involved. Patients who needed sedation for more than 2 consecutive days after undergoing surgery in the Pediatric Surgery Department of our hospital were enrolled for the study. Fifty-six patients (5-14 years old) were randomly divided into midazolam and propofol treatment groups (N = 28 each in each group). Pediatric patients received midazolam or profolol via continuous intravenous administration, and their plasma cytokine levels were compared after 48 h. Cultured rat C6 brain glioma cells were pretreated with a range of concentrations of midazolam or propofol for 60 minutes prior to incubation with 10 ng/mL IL-1ß in serum-free medium or vehicle for 36 h. IL-6 concentration was subsequently measured using ELISA. In comparison with levels measured before the infusion of midazolam for 48 h, concentrations of all cytokines decreased, with the differences in IL-1ß, IL-8, and TNF-α concentrations reaching significance (all P < 0.05). Midazolam significantly suppressed the IL-1ß-induced release of IL-6 in rat C6 glioma cells. This inhibition was concentration-dependent between 0.3 and 3 µM, with 3 µM concentration of midazolam decreasing the IL-1ß-induced release of IL-6 by 43.58%. Midazolam can significantly inhibit the release of cytokines in pediatric patients after surgery. One of the mechanisms may be the inhibition of IL-1ß- induced release of IL-6 in the central nervous system.

A comparative study of the retention or removal of jejunal mucosa during pancreatic duct to jejunal anastomosis.

AIM: The aim of this study was to compare the two anastomosis methods, that is, the retention or the removal of the jejunal mucosa during pancreatic duct to jejunal anastomosis after pancreaticoduodenectomy (PD). METHODS: For this purpose, 46 PD patients were randomly and equally divided into groups A and B. In group A, the remnant pancreas was inserted 3 cm into the jejunum and the connecting part was sutured. In group B, the jejunal mucous membrane was cauterized 3 cm at the end, the remnant pancreas was sutured with the jejunal muscle layer, and the jejunum and pancreas were sutured together. RESULTS: We found that in group A, the reoperation rate due to delayed bleeding was 13% (3/23) and the ulcer bleeding around anastomosis was 4.3% (1/23). In group B, the reoperation rate due to bleeding was 4.3% (1/23) and the incidence of postoperative pancreatic fistula was 17.4% (4/23). The duration of pancreaticojejunostomy operation in group A (46 ± 0.34 min) was shorter than in group B (P<0.001). CONCLUSION: We, therefore, concluded that the pancreatic duct to jejunal anastomosis with retained jejunal mucosa was a simple and easy to perform method while it also excluded the risk of postoperative pancreatic fistula formation.

An SNP in the MyoD1 gene intron 2 associated with growth and carcass traits in three duck populations.

Myogenic differentiation 1 (MyoD1) genes belong to the MyoD gene family and play key roles in growth and muscle development. This study was designed to investigate the effects of variants in the MyoD1 gene on duck growth and carcass traits. Three duck populations (Cherry Valley, Jingjiang, and Muscovy) were sampled, their growth and carcass traits were measured, and they were genotyped using the PCR-RFLP method. The results showed one novel polymorphism, an alteration in intron 2 of the MyoD1 gene (A to T). It was associated with the traits of weight at 8 weeks, carcass weight, breast muscle weight, leg muscle weight, eviscerated percentage, percentage of leg muscle weight, dressing percentage, and lean meat percentage. This alteration in intron 2 of MyoD1 may be linked with potential major loci or genes affecting some growth and carcass traits.

One novel SNP of growth hormone gene and its associations with growth and carcass traits in ducks.

In this study, the growth hormone (GH) gene was studied as a candidate gene for growth and carcass traits of three duck populations (Cherry Valley duck, Muscovy duck and Jingjiang duck). Three pairs of primers were designed to detect single nucleotide polymorphisms of introns 2, 3 and 4 of the GH gene by polymerase chain reaction-restriction fragment length polymorphism and sequencing methods. Only the products amplified from intron 2 displayed polymorphism. The results showed one novel polymorphism: a variation in intron 2 of GH gene (C172T, JN408701 and JN408702). It was associated with some growth and carcass traits in three duck populations including birth weight, 8-week weight, carcass weight, breast muscle weight, leg muscle weight, eviscerated weight, lean meat rate, dressing percentage, etc. And the TT and CT genotypes were associated with superior growth and carcass traits in carcass weight, dressing percentage and percentage of eviscerated weight. Therefore, the variation in intron 2 of GH may be a molecular marker for superior growth and carcass traits in above duck populations.

Pineal parenchymal tumours: minimum apparent diffusion coefficient in prediction of tumour grading.

Retrospective assessment was performed of the minimum apparent diffusion coefficient (minADC) together with quantitative assessment of the histopathological features of resected tumour tissue and the Ki-67 labelling index (LI) for predicting pineal parenchymal tumour (PPT) grade. Magnetic resonance images of tumours from 26 male and female patients (mean age 27.7 years) with pathologically confirmed PPTs, comprising 10 pineocytomas (PCs), seven pineal parenchymal tumours of intermediate differentiation (PPTIDs) and nine pineoblastomas (PBs), were reviewed retrospectively. Using ADC maps derived from isotropic diffusion-weighted images, the minADC value of each tumour was determined postoperatively from several regions of interest defined in the tumour, excluding cystic, necrotic, haemorrhagic or calcified components. Surgical intervention was undertaken in all cases. The Ki-67 LI was measured in surgical specimens. Mean minADC and Ki-67 LI showed significant differences among PCs, PPTIDs and PBs, and minADC was negatively correlated with Ki-67 LI. It is concluded that the minADC of PPTs provide useful additional information when predicting tumour grading.

In vivo anti-melanoma efficacy of allo-restricted CTLs specific for melanoma expanded by artificial antigen-presenting cells.

Cytotoxic CD8(+) T cells are key effectors in the immunotherapy of malignant and viral diseases. However, autologous T cell responses to tumor antigens presented by self-MHC are usually weak and ineffective. Allo-restricted T cells represent a potent source of tumor-specific T cells for adoptive immunotherapy. This study reports in vivo anti-melanoma efficacy of the pTRP2-specific allo-restricted CTLs expanded from the BALB/c splenocytes by multiple stimulations with aAPCs made by coating H-2K(b)-Ig/pTRP2 dimeric complexes, anti-CD28 antibody, 4-1BBL molecules and CD83 molecules to cell-sized latex beads. The induced allo-restricted CTLs exhibited specific lysis against RMA-S cells pulsed with the peptide pTRP2 and H-2K(b+) melanoma cells expressing TRP2, while a murine Lewis lung carcinoma cell line 3LL could not be recognized by the CTLs. The peptide-specific activity was inhibited by anti-H-2K(b) monoclonal antibody Y3. Adoptive transfer of the allo-restricted CTLs specific for malignant melanoma expanded by the aAPCs can mediate effective anti-melanoma response in vivo. These results suggested that the specific allo-restricted CTLs expanded by aAPCs coated with an MHC-Ig/peptide complex, anti-CD28 antibody, 4-1BBL and CD83 could be a potential option of specific immunotherapy for patients with malignant melanoma.

Monitoring release of ketoprofen enantiomers from biodegradable poly(D,L-lactide-co-glycolide) injectable implants.

A stereoselective reversed-phase HPLC assay was developed that could simultaneously quantify S-(+) and R-(-) enantiomers of ketoprofen in release samples. Racemic ketoprofen (rac-KET) and its S-(+) enantiomer (S-(+)-KET) were dissolved in an injectable viscous polymer solution consisting of the biodegradable poly(D,L-lactide-co-glycolide, 70:30) (D,L-PLG) and a solvent, N-methyl-2-pyrrolidone (NMP). Once injected into an aqueous environment, the polymeric mixture solidified into a solid implant due to the leaching of NMP. In vitro release studies show that such implants with ketoprofen can provide sustained release of the drug lasting about three months in a pH 7.4 release medium. Moreover, a preferential faster S-(+)-KET release over R-(-)-KET was observed for the implants containing 4%, 7%, and 10% of racemic ketoprofen in the neutral pH 7.4 release medium. Stereoselective release was minimal in the first 42 days in vitro but became very pronounced at later time points. When S-(+)-KET was incorporated into the polymeric mixture, its release was also faster than that of the racemic ketoprofen, confirming the stereoselective release of ketoprofen from the d,l-PLG implants. The observed stereoselective release of KET at pH 7.4 was most likely produced by chiral interactions between KET enantiomers and transiently produced D-lactic acid or L-lactic acid rich domains within the implants during D,L-PLG degradation. However, such stereoselective release was not observed in pH 10.0 release medium, probably due to a much faster and homogeneous polymer degradation. The study suggests possible stereoselective release of racemic drugs from D,L-PLG microspheres and implants in vivo.

Human insulin from a precursor overexpressed in the methylotrophic yeast Pichia pastoris and a simple procedure for purifying the expression product.

The methylotrophic yeast Pichia pastoris, which proved successful in producing many heterologous proteins, was used to express an insulin precursor. A transformant with a high copy number of the gene integrated into the chromosome was obtained by the dot-blotting method. In high-density fermentation using a simple culture medium composed mainly of salt and methanol, the expression level reached 1.5 g/L. A simple two-step method was established to purify the expression product from the culture medium with an overall recovery of about 80%. After tryptic transpeptidation, human insulin with full receptor binding capacity and biological activity was obtained. In the presence of zinc, the recombinant human insulin could be crystallized in the rhombohedral form.

Four new monomeric insulins obtained by alanine scanning the dimer-forming surface of the insulin molecule.

The residues A21Asn, B12Val, B16Tyr, B24Phe, B25Phe, B26Tyr and B27Thr, buried in the dimer of insulin, were identified by means of alanine-scanning mutagenesis. The receptor binding activity, in vivo biological potency and self-association properties of the seven single alanine human insulin mutants were determined. Four of the seven single alanine mutants, [B12Ala]human insulin, [B16Ala]human insulin, [B24Ala]human insulin and [B26Ala]human insulin, are monomeric insulin, which indicates that B12Val, B16Tyr, B24Phe and B26Tyr are crucial for the formation of insulin dimer. The monomeric [B16Ala]human insulin and [B26Ala]human insulin retain 27 and 54% receptor binding activity, respectively, and nearly the same in vivo biological potency compared with native insulin, so they could be developed as the fast-acting insulin.

Residential radon exposure and lung cancer in Swedish women.

A case-control study was undertaken to investigate the role of residential radon exposure for lung cancer. The study included 210 women with lung cancer diagnosed from 1983-1986 in the county of Stockholm and 191 hospital and 209 population controls. Interviews provided information on lifetime residences and smoking. Radon concentrations measured in 1,573 residences of the study subjects showed a lognormal distribution with arithmetic and geometric means of 127.7 and 96.0 Bq m-3, respectively. Lung cancer risks tended to increase with estimated radon exposure, reaching a relative risk of 1.7 (95% confidence interval: 1.0-2.9) in women having an average radon level exceeding 150 Bq m-3 (4 pCi L-1). Stronger associations were suggested in younger persons and risk estimates appeared to be within the same range as those projected for miners. However, further studies are needed to clarify the level of risk associated with exposure to residential radon.

Delayed radiation encephalopathy after radiotherapy for nasopharyngeal cancer: a CT study of 45 cases.

The CT features of 45 cases of delayed radiation encephalopathy (including radiation necrosis) following radiotherapy for nasopharyngeal carcinoma are reported. The brain lesions were uni- or bilateral and involved mainly the white matter and subsequently the gray matter of the lower portion of the brain included within the portals of irradiation and its vicinity. The lesions were edematous and hypodense on CT and showed postcontrast enhancement in 50% of the cases. Within the period of follow-up (1-5 years), the lesions showed remissions and exacerbations and in some cases stabilized. In addition, there was progressive cerebral atrophy, manifesting itself mainly as dilatation of the temporal horns, the neighboring cisterns, and sylvian fissures. In some cases that were followed for a long time, the cerebral lesions showed either foci of calcification or encephalomalacia and/or porencephaly.