[Application of immune combination therapy in MSS/pMMR-type colorectal cancer: current status and future perspectives].

In recent years, immune checkpoint inhibitors (ICIs) have been widely used in malignant solid tumors with remarkable efficacy. However, in colorectal cancer (CRC), ICIs have shown significant therapeutic effects only in patients with highly microsatellite unstable/mismatch repair-deficient metastatic CRC and these patients are only a minority of all CRC patients. In contrast, the majority of patients, those with microsatellite stable (MSS)/mismatch repair-complete (pMMR)-type metastatic CRC, could hardly benefit from ICI monotherapies, and immune combination therapies have become the key to solveing this clinical challenge. This article introduces the common patterns and possible mechanisms of immune-combination therapies for MSS/pMMR-type CRC, the exploration and progress made in the application of immune-combination therapies, as well as the possible predictive markers of efficacy of immune therapies. The prospects and directions of ICIs in the treatment of MSS/pMMR-type CRC are also discussed.

[Follow-up analysis of sex hormone levels and prognosis in women after hematopoietic stem cell transplantation].

Objective: To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT. Methods: Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results: The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions: The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

[Research on early warning model of the hearing loss of workers exposed to noise].

Objective: To explore the change of hearing threshold of workers exposed to noise, establish an individual-based hearing loss early warning model, accurately and differentiated the health of workers exposed to noise. Methods: In September 2019, all physical examination data of 561 workers exposed to noise from an enterprise were collected since their employment. Three indicators of average hearing threshold of the better ear, namely, at high frequency, 4000 Hz and speech frequency, were constructed. The generalized estimating equation (GEE) was used to adjust gender and age and establish the warning model of each indicator. Finally, sensitive indicators and warning models were screened according to AUC and Yoden index. Results: Among the 561 workers exposed to noise, 26 (4.6%) workers had hearing loss. The sensitivity indicators were the average hearing threshold at speech frequency ≥20 dB, high frequency ≥30 dB and 4000 Hz ≥25 dB. The AUC of each index was 0.602, 0.794 and 0.804, and the Youden indexes were 0.204, 0.588 and 0.608, respectively. In GEE of hearing loss warning models, high-frequency hearing threshold ≥20 dB and 4000 Hz hearing threshold ≥25 dB were the optimal models, with AUC of 0.862. Conclusion: Combined with the changes of individual hearing threshold over the years, can accurately assess the risk of individual hearing loss of workers exposed to noise.

[Exploration of phase angle used to construct PG-SGA nutritional assessment and prediction model for malignant tumor patients].

Objective: To explore the value of phase angle (PA) in constructing a predictive model of nutrition evaluation for tumor patients. Methods: A retrospective analysis was performed on 1 129 patients with malignant tumors hospitalized in the Cancer Center of Changzhi People's Hospital from June 2020 to February 2021. PA values of six parts of the body were measured by the body composition analyzer, including: left arm (LA), right arm (RA), left leg (LL), right leg (RL), the trunk (TR), and the whole body (WB). Patients' body mass index (BMI) was calculated and patient-generated subjective global assessment (PG-SGA) was assessed. The differences of PA values of six parts were compared and their correlations with BMI and PG-SGA in combination with age, gender and tumor disease types were analyzed, binary classification regression on BMI and PG-SGA was performed, and the functions of the best prediction model was fitted. Decision tree, random forest, Akaike information criterion in a Stepwise Algorithm (stepAIC) and generalized likelihood ratio test were used to select appropriate variables, and the logit logistic regression model was used to fit the data. Results: Comparing the PA values of six parts in pairs, it was found that the PA values of LA and RA, LL and RL, and TR and WB were linearly correlated and the coefficient was close to 1 (P<0.001). Binary classification regression was performed for BMI and PG-SGA, respectively. In order to make the data have clinical significance, 18.5 kg/m(2) was used as the classification point for BMI, 4 and 9 were used as the classification points for PG-SGA score, and the models of A, B and C were obtained. Suitable variables including PA-LA, PA-TR and tumor disease types were used as variables to fit BMI classification; BMI, PA-LA and age were used as variables to fit the PG-SGA model with 9 as the classification point. PA-LA, PA-TR, BMI, age and tumor disease types were used as variables to fit the PG-SGA model with 4 as the classification point. In this study, the predicted values of models A, B and C obtained by R-studio were imported into SPSS 26.0 software, and the cut-off values of classification were obtained by the receiver operating characteristic (ROC) curve. The ROC analytic results showed that the best cut-off values of Model A, B and C were 0.155, 0.793 and 0.295. Model A recommended when the probability is >0.155, a patient's nutritiond tatus should be classified as BMI < 18.5 kg/m(2) group. Model B recommended that PG-SGA<9 group be classified as the probability is >0.793. Model C recommended that PG-SGA < 4 group should be classified when probability is >0.295. Conclusions: The PG-SGA classification prediction model is simple to operate, and the nutritional status of patients can be roughly divided into three groups: normal or suspected malnutrition group (PG-SGA<4), moderate malnutrition group (4≤PG-SGA<9), and severe malnutrition group (PG-SGA≥9). This model can more efficiently predict the nutritional status of cancer patients, greatly simplify the nutritional assessment process, and better guide the standardized treatment of clinical malnutrition.

[Kawasaki disease complicated with mild encephalitis/encephalopathy with a reversible splenial lesion: A case report and literature review].

We reported a pediatric case of Kawasaki disease complicated with mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) from Beijing Tsinghua Changgung Hospital. The clinical data were retrospectively analyzed and the related literature was reviewed. The clinical features, treatment and prognosis of the disease were summarized to improve recognition of Kawasaki disease complicated with MERS. A 7-year-old boy was diagnosed with Kawasaki disease due to continuous high fever for 6 d, accompanied by strawberry tongue, conjunctival congestion, erythema-like hyperemia rash, and cervical enlarged lymph nodes. And treatment was started with intravenous immunoglobulin (IVIG: 2 g/kg) and oral aspirin [40 mg/(kg·d)]. Twenty-four hours after the treatment of IVIG, the patient' s fever persisted and in addition he developed headache and drowsiness. His cranial magnetic resonance imaging (MRI) demonstrated a localized lesion in the splenium of the corpus callosum with high intensity signal on diffusion-weighted images (DWI) and T2-weighted, and low intensity signal on apparent diffusion coefficient (ADC) and T1-weighted. Based on these findings, he was diagnosed with MERS-complicated Kawasaki disease. Methylprednisolone [2 mg/(kg·d)] treatment was started intravenously, and within several hours he was afebrile and the neurological symptoms disappeared. A follow-up MRI was conducted after 1 week was normal. He was discharged without any neurological sequelae and coronary artery lesions. A total of 12 qualified foreign literature were retrieved, with no Chinese literature searched. Seventeen children were reported, the median age was 6.5 years (range: 1-14 years), among them 11 cases were children over 5 years old, and 4 cases were complicated with coronary artery lesions. All children had neurological symptoms, such as consciousness disorder, visual hallucination or convulsion. MRI conformed to MERS imaging changes. After active treatment, the neurological manifestations and radiological abnormalities completely disappeared, leaving no neurological sequelae. Kawasaki disease complicated with MERS had not been reported in China by now. Literature that identified Kawasaki disease complicated with MERS mostly occurred in children over 5 years old. Cranial MRI examination is helpful for early diagnosis. Timely treatment can reverse MERS in a short time, without neurological sequelae left.

[The value of MR diffusion tensor imaging in assessing white matter changes in short-term methamphetamine withdrawal].

Objective: To explore the value of MRI diffusion tensor imaging (DTI) in the white matter changes of short-term methamphetamine (MA) abstinence. Methods: The data of DTI, demographics features, general information of addiction and impulsivity scale eleven (BIS-11) of 55 short-term MA addicts who were from Changsha, Zhuzhou and Yueyang compulsory detoxification centers in Hunan province, including 40 males and 15 females, aged 14-45 (37.24±7.31) years old, and 52 healthy controls, including 40 males and 12 females aged 18-59 (40.3±9.1) years were collected prospectively from August 2017 to December 2018. The differences of DTI indicators between the two groups were compared by tract-based spatial statistics (TBSS), and then the correlation between the different indicators and the age of first MA use, time of MA use, daily dose used, BIS-11 score were performed. Results: There were significant differences in BIS total score(P<0.001), BIS motivational impulsivity(P<0.001) and BIS attentional impulsivity(P=0.003) between MA group and healthy control group in short-term withdrawal. And compared with the healthy control group, the fractional anisotropy (FA) (0.58±0.02 vs 0.56±0.02,0.77±0.02 vs 0.75±0.04,0.79±0.04 vs 0.76±0.06; all P<0.05), axial diffusivity (AD) (0.57±0.01 vs 0.56±0.02,P=0.001) and mean diffusivity (MD) (0.66±0.02 vs 0.65±0.02,0.52±0.07 vs 0.51±0.06; both P<0.05)values in the MA group were all increased (P<0.05), but there was no significant difference in the radial diffusivity (RD) value (P>0.05). The white matter areas with increased FA value were located in the knee and body of corpus callosum, bilateral anterior corona radiata and left superior corona radiata; the areas with increased AD value were located in the knee, body and pressure of corpus callosum, bilateral anterior limb of internal capsule, posterior limb of internal capsule, anterior, superior and posterior corona radiata, external capsule and superior longitudinal fasciculus; and the areas with increased MD value were mainly located in the right superior longitudinal fasciculus, anterior and posterior limb of internal capsule. The corpus callosum, where there was a difference in FA between the two groups, was positively correlated with the daily dose of MA (r=0.301, P=0.026). Conclusion: MA addicted individuals with short-term withdrawal have white matter edema and damage, and the degree of corpus callosum damage is positively correlated with the daily dose of MA,which is helpful to understand the pathophysiological process of white matter damage in the nervous system and the potential mechanism of neuropsychiatric symptoms in short-term withdrawal MA addicted individuals.

Population genetic structure and its implication in the conservation of Schizopygopsis pylzovi in Yellow River as inferred from mitochondrial DNA sequence analysis.

To assess the genetic diversity, structure, and population dynamics of Schizopygopsis pylzovi, we examined the changes in mitochondrial DNA sequences (the mtDNA control region and the Cyt b gene; 1835 bp) in 304 individuals from nine populations. The samples were segregated into 112 haplotypes, with high haplotype diversity and low nucleotide diversity. The haplotype diversity was highest in the Minhe (HS) range of Huangshui River and lowest in the Weiyuan (WY) range of Weihe River. Analysis of molecular variance showed that 69.64% of the total genetic variance was contributed by within-the-group variation and 30.36% was contributed by among-the-group variation. Pairwise FST revealed significant divergence between the populations. The FST between the MT and WY was highest, and that between the YZ and YJ was lowest. The neighbor-joining phylogenetic tree demonstrated that all geographic populations were not monophyletic, but overlapped each other, indicating that the duration of geographical isolation was not long enough or the populations had not yet reached significant genetic isolation or differentiation at the monophyletic level. Tajima's D and Fu's Fs were negative and statistically significant, indicating that S. pylzovi had experienced certain population expansion events, which is consistent with the hypothesis that the headwater area of the Yellow River was dramatically affected by the geological and climatic upheaval during the Quaternary ice age. Our analysis indicated that the management units corresponding to the WY population should be managed and conserved first. In situ conservation is first recommended to protect the original habitat from further destruction.

[Dynamic alteration of microRNA in high phosphorus induced calcification of vascular smooth muscle cell].

OBJECTIVE: To study the change of microRNA during the early stage of high phosphorus induced vascular smooth muscle cell (VSMC) calcification and its related mechanism. METHODS: The in vitro calcification model was created through stimulating VSMC cell line A7r5 with high Pi (2.6 mmol/L) for 7 d. The calcification was validated through ocresolphthalein complexone colorimetry to detect the cellular calcium content, real-time PCR to measure the calcification-related gene expression and alizarin red staining to observe the formation of calcium nodules. Based on the cell calcification model, microRNA microarray array was applied to screen the profiles of microRNA expression in VSMC following high Pi stimulation for different periods (0, 3 and 12 h). The array data were analyzed by TAM tool to explore the activated signaling pathway. RESULTS: The calcium content of A7r5 cells induced by high Pi was increased 9.6 times high as cells without Pi treatment (P<0.05). VSMC contractile phenotype genes (SM-α actin, SM22) were down-regulated (P<0.05), while calcification-related genes (BMP2, MSX2, Runx2) were up-regulated (P<0.05) in VSMC stimulated by high Pi. The calcium nodules were obviously formed in cells after 7 d high Pi treatment. In microarray experiment, 680 individual microRNAs were detected in high Pi-treated VSMCs at different time points (0, 3 and 12 h). Among these genes, miR-183, miR-664 and miR-9* were increased whereas miR-542-5P, let-7f and miR-29a were decreased in time-dependent manners. Twenty-six kinds of signaling pathways, including cell apoptosis, differentiation and proliferation, were significantly activated. All these activated pathways were associated with calcification. CONCLUSION: This study implies that microRNA changed in high Pi-induced VSMCs may involve in the process of calcification.

Association between G-217A polymorphism in the AGT gene and essential hypertension: a meta-analysis.

Numerous studies have evaluated the association between the angiotensinogen (AGT) G-217A gene polymorphism and essential hypertension risk. However, the results have been inconsistent. We examined whether the AGT G-217A gene polymorphism confers essential hypertension risk by conducting a meta-analysis. We conducted a literature search of the Google Scholar, PubMed, and China National Knowledge Infrastructure databases for relevant studies that examined the G-217A polymorphism and risk of essential hypertension. Statistical analyses were carried out using Stata 12.0 to combine all relevant studies. Crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to estimate the strength of this association. A total of 2017 patients with psoriasis and 1708 controls from 7 comparative studies were included in this meta-analysis. We found a significant association between the AGT G-217A gene polymorphism and the risk of essential hypertension (AA vs GG: OR = 2.52, 95%CI = 1.68-3.78; AA vs GA: OR = 2.26, 95%CI = 1.48-3.45; dominant model: OR = 0.38, 95%CI = 0.26-0.57; recessive model: OR = 1.20, 95%CI = 1.03-1.39). Further stratified analyses were conducted by ethnicity and sample size and produced similar results. No evidence of publication bias was found. This meta-analysis confirms that the AGT G-217A gene polymorphism is associated with essential hypertension susceptibility.

[Endoscopic full-thickness resection in near clinical complete response rectal cancer after neoadjuvant therapy].

Objective: To investigate the safety and feasibility of endoscopic full-thickness resection (EFTR) in the treatment of near-clinical complete response (near-cCR) rectal cancer after neoadjuvant therapy. Methods: A 74-year-old female patient with cT3N0M0 stage rectal adenocarcinoma who refused radical surgery for rectal cancer underwent neoadjuvant chemoradiotherapy (5 cycles of CapeOx chemotherapy and concurrent radiotherapy for 25 sessions) after multidisciplinary team discussion. One month after completing neoadjuvant treatment, reassessment including digital rectal examination, colonoscopy, and pelvic enhanced magnetic resonance imaging suggested near-cCR. Despite this, the patient requested rectal-preserving therapy. Subsequently, EFTR was performed five weeks after completion of neoadjuvant treatment. Postoperatively, supportive care including fasting, antimicrobial therapy, and nutritional support was provided. The patient started a liquid diet on the 6th day postoperatively and was discharged on the 13th day. Results: Pathological analysis revealed tubular adenoma with low-grade epithelial dysplasia, with negative margins and negative involvement of the base. During one-year follow-up, there were no signs of local regrowth or distant metastasis, and satisfactory anal function was observed. Conclusion: EFTR is safe and feasible in patients with near-cCR rectal cancer after neoadjuvant therapy. This approach should be considered after thorough evaluation of the patient's condition.

[Natural history and risk factors of IgE-mediated cow's milk protein allergy in infants].

Objective: To investigate the natural history and risk factors for continued allergy in infants with IgE-mediated cow's milk protein allergy (CMPA). Methods: This was a prospective cohort study that included 72 infants under 24 months of age diagnosed with IgE-mediated CMPA in the allergy clinic of the Children's Hospital, Capital Institute of Pediatrics from October 2019 to November 2020. General information, clinical manifestations, serum total IgE, cow's milk specific IgE, and cow's milk protein component specific IgE were collected. Follow-ups were conducted at 24 and 36 months of age, and the patients were divided into the persistent allergy group and the tolerance group based on whether they developed cow's milk tolerance at 36 months of age. Mann-Whitney U test, chi-square test, and binary Logistic regression were used for intergroup comparison and multivariate analysis. Results: Among the 72 CMPA children, there were 42 boys and 30 girls, with an age of 10 (7, 15) months at enrollment. Cow's milk protein tolerance was observed in 32 cases (44%) and 46 cases (64%) at 24 and 36 months of age, respectively. There were 26 cases in the persistent allergy group and 46 cases in the tolerance group. The proportion of respiratory symptoms, history of wheezing, positive specific IgE for α-lactalbumin and the total IgE level in the persistent allergy group were higher than that in the tolerance group (7 cases (27%) vs. 0, 6 cases (23%) vs. 2 cases (4%), 67% (14/21) vs. 26% (10/39), 225 (151, 616) vs. 48 (21, 185) kU/L, χ2=10.82, 4.16, 9.57, Z=4.07, all P<0.05). Multivariate Logistic regression analysis showed that anaphylaxis (OR=21.14, 95%CI 2.55-175.14, P=0.005), a history of allergic rhinitis (OR=5.94, 95%CI 1.54-22.86, P=0.005), elevated milk specific IgE (OR=1.04, 95%CI 1.01-1.08, P=0.024), and positive casein specific IgE (OR=6.64, 95%CI 1.39-31.69, P=0.018) were risk factors for continuous CMPA. Conclusions: Most infants with IgE-mediated CMPA can achieve tolerance within 3 years. Anaphylaxis, a history of allergic rhinitis, elevated milk specific IgE levels, and casein sensitization are risk factors for continuous allergy.

Pioglitazone induces regression and stabilization of coronary atherosclerotic plaques in patients with impaired glucose tolerance.

AIMS: To observe the effects of pioglitazone on coronary plaque area, plaque burden, serum high-sensitivity C-reactive protein, adiponectin and plasma endothelin-1 levels in patients with impaired glucose tolerance and coronary borderline lesions. METHODS: Thirty patients were randomly divided into two groups: a pioglitazone group and a control group. The latter was administered placebo in addition to standard therapy; the former pioglitazone 15 mg/d in addition to standard therapy. Before treatment and 6 months later, left ventricular ejection fraction, serum lipid profile, high-sensitivity C-reactive protein, adiponectin and plasma endothelin-1 levels were detected. Coronary plaque area and plaque burden were examined using intravascular ultrasound. RESULTS: No significant differences were found in left ventricular ejection fraction and serum lipid levels pre- and post-trial. Compared with the control group, 6 months' treatment with pioglitazone significantly decreased coronary plaque burden (50.7 ± 11.1 vs. 64.1 ± 10.3%, P < 0.05), plaque area (6.22 ± 2.03 vs. 8.31 ± 4.29, P < 0.05), thin-cap fibroatheroma prevalence (11 vs. 22%, P < 0.05) and percentage of necrotic core area (16 ± 8 vs. 31 ± 7%, P < 0.05). Compared with the control group, serum high-sensitivity C-reactive protein and plasma endothelin-1 levels were significantly lower and adiponectin level significantly higher in patients in the pioglitazone group. Serum adiponectin level was negatively correlated with plasma endothelin-1 level and coronary plaque area (r = 0.739 and -0.431, respectively, both P < 0.05). CONCLUSIONS: Pioglitazone may induce regression and stabilization of coronary atherosclerotic plaques. The mechanisms might involve inhibition of inflammation, increase in adiponectin level and improvement in endothelial function.

[Clinical characteristics of IgE-mediated cow's milk protein allergy in children].

Objective: To analyze the clinical features of IgE-mediated cow's milk protein allergy (CMPA) in children aged 0-5 years. Methods: This cross-sectional study collected the data on children diagnosed with CMPA in the Department of Allergy at the Children's Hospital of the Capital Institute of Pediatrics from October 2019 to November 2020 and improved peripheral blood routine,total IgE defection, milk specific IgE (sIgE) defection,SPT and milk component defection,diagnosis of severe anaphylaxis based on clinical manifestations. Rank-sum test and chi-square test are used for statistical analysis of clinical characteristics between groups. Results: A total of 106 children (67 boys and 39 girls) were enrolled with the age of 15 (8, 34) months, including 42 cases (≤ 1 year of age), 39 cases (>1-<3 years of age) and 25 cases(≥3 years of age), the onset age of 6 (5, 8) months. Among them, 95 cases (89.6%) were reacted after consuming milk or its products, 42 cases (39.6%) had reaction due to skin contact and 11 cases (10.4%) reacted after exclusive breastfeeding. The onset time of milk product consumption was 45 (1, 120) min, skin contact pathway was 10 (5, 30) min and symptoms in breastfeeding pathway was 121 (61, 180) min. There was statistical difference among the time of symptoms (χ2=77.01, P<0.001).The cutaneous reaction was most common (100 cases, 94.3%), followed by digestive (20 cases, 18.9%) and respiratory (16 cases, 15.1%), and the nervous symptoms (1 case, 0.9%) were uncommon and 24 cases (22.6%) had at least one episode of anaphylaxis. There were 87 cases (82.1%) also diagnosed with other food allergies, 94 cases (88.7%) with previous eczema, 57 cases (53.8%) with history of rhinitis, and 23 cases (21.7%) with history of wheezing. The total IgE level was 191.01 (64.71, 506.80) kU/L, and the cow's milk sIgE level was 3.03 (1.11, 15.24) kU/L. The maximum diameter of the wheal in SPT was 8.2 (4.0, 12.0) mm. Component resolved diagnosis showed that 77 cases (81.9%) were sensitized to at least one out of 4 main components, including casein, α lactalbumin, ß lactoglobulin and bovine serum albumin.The possibility of anaphylaxis in children with milk sIgE grade Ⅳ-Ⅵ was higher than that in children with grade 0-Ⅲ (57.7% (15/26) vs. 12.5% (10/80), OR=9.545, 95%CI 3.435-26.523). Children with milk SPT ≥+++ had a higher probability of anaphylaxis than those with milk SPT ≤++ (34.4% (11/32) vs. 11.5% (3/26), OR=4.016, 95%CI 0.983-16.400). Anaphylaxis were more common in α lactalbumin positive children than in negative children (34.3% (13/38) vs. 14.2% (8/56), χ2=1.23，P=0.042). Conclusions: CMPA in children has early onset and diversified clinical manifestations, which are mainly cutaneous symptoms. Most children are sensitized to at least one allergen component. Serum sIgE level, SPT reaction and allergen components play important roles in the diagnosis and evaluation of CMPA, and higher milk sIgE level may predict a higher risk of anaphylaxis.

[Clinical and prognostic values of TP53 mutation in patients with B-lineage acute lymphoblastic leukemia].

Objective: To investigate the survival and prognosis of B-lineage acute lymphoblastic leukemia (B-ALL) patients with TP53 mutation. Methods: The clinical data of 479 newly diagnosed B-ALL patients treated in the First Affiliated Hospital of Soochow University from January 2016 to December 2019 were retrospectively analyzed. Results: Among 479 B-ALL patients, 34 cases (7.1%) were positive for TP53 gene mutation, and a total of 36 TP53 mutations were detected, including 10 frameshift gene mutations (27.8%) , 23 missense mutations (63.9%) and 3 nonsense mutations (8.3%) . A total of 34 (94.4%) mutations were located in the DNA binding domain (exons 5-8) .The average number of mutated genes in patients with TP53 gene mutation (2.3) and the group without TP53 gene mutation (1.1) were statistically different (P<0.001) . The proportion of Ph positive and Ph-like positive patients in the TP53 gene mutation negative group was significantly higher than that of the TP53 mutation positive group, and the difference was statistically significant (P<0.001) . The 3-year OS and EFS rates of the TP53 gene mutation negative group were significantly higher than those of the TP53 gene mutation positive group. The differences in OS and EFS rates between the two groups were statistically significant (χ(2)= 4.694, P = 0.030; χ(2)= 5.080, P= 0.024) . In the multivariate analysis, failure to achieve remission (CR) after one course of induction chemotherapy was an independent adverse prognostic factor affecting OS.Of the 34 patients with TP53 mutation, 16 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the CR(1) state, and 2 patients with recurrence after transplantation obtained CR(2) after infusion of donor-derived anti-CD19 chimeric antigen receptor T (CAR-T) cells. Among the 11 patients with TP53 gene mutation who relapsed during consolidation chemotherapy, 6 received anti-CD19 CAR T cell therapy, 4 patients achieved remission and minimal residual disease (MRD) turned negative, followed by bridging allo-HSCT, and 2 of them sustained CR. Conclusion: Missense mutations are the most common in B-ALL patients with TP53 gene mutation, and the majority of mutations were located in the DNA binding domain. B-ALL patients with TP53 gene mutation should undergo allo-HSCT as soon as possible after CAR-T cell therapy has cleared the MRD after recurrence. B-ALL patients with TP53 gene mutation still have a higher recurrence rate after allo-HSCT, and the infusion of donor-derived CAR-T cells can achieve better sustained remission.

[Development of Risk Assessment Index System on HIV infection among young students based on Delphi method].

Objective: To develop a Risk Assessment Index System (RAIS) on HIV infection among young students based on Delphi method and to provide individual HIV infection risk assessment, targeted prevention and control measures. Methods: Delphi method was applied to determine the index system and weight of the assessment tool through three rounds of expert consultation and overall consideration of opinions and suggestions from 19 experts. Results: The positivity coefficients of three rounds of expert consultation were 100%. The authority coefficient of experts was between 0.887 and 0.945. The Kendall's W coefficients through first, second and third round specialist consultation was 0.379, 0.329 and 0.248, respectively (all P<0.001). The coefficients of variation in the third round were all less than 0.25, indicating that experts' opinion tend to be consistent and the results are highly reliable. The HIV infection risk assessment index system among young students consisted of 7 first grade indices and 54 second grade indices, of which weight was calculated. Conclusions: The RAIS on HIV infection for young students was initially established based on Delphi method, and could be used in the development of HIV infection risk assessment tools for personalized prevention and intervention among young students. However, the reliability, validity and effect of this assessment index system need to be further evaluated.

[Cluster analysis on survey of sexual health characteristics and health education demands in young students].

Objective: To explore the difference of sexual health characteristics and demands in students in different groups, and provide the basis for targeted sexual health eduction for AIDS prevention in young students. Methods: A survey was conducted based on the requirement of health education about sexual health and AIDS prevention in young students by the education department of Guangdong province. A two-step cluster analysis was performed on the survey data obtained by convenient sampling, the variables and number of clusters included were determined by combination of analysis results and professional knowledge. The demographic characteristics, the content and form of sexual health education needed were compared among different groups. Results: Survey data of 3 884 students were collected, and six variables were used for classification: cognition or occurrence masturbation, sexual behavior, frequency of sexual information acquisition, number of acceptable sex partners and AIDS knowledge awareness rate. By these variables, the students were classified into three levels of risk groups: high risk group (46.6%), medium risk group (39.9%) and low risk group (13.5%). As for demographic characteristics, high risk group, with a median age of 19 years, had the highest proportions of boys (65.9%), students with non-heterosexuality orientation (15.2%), urban residents (58.2%), only children (30.8%) and undergraduates (54.7%). Medium risk group, with a median age of 19 years, had the highest proportions of girls (82.7%) and vocational college students (34.0%). Low risk group, with a median age of 18 years, had the highest proportions of rural residents (52.4%), non-only child (80.6%), senior high school students (41.3%), non-boarding students (17.5%) and students without internship and part-time job experience (43.2%). In terms of health education demands, high risk group had a higher demand of information about self-identity, sexual safety, sexual decision making, contraception, abortion, and sexually transmitted disease or AIDS prevention. Medium risk group paid more attention to value on love and marriage, sexual assault. Low risk group showed a higher demand of adolescent physiology knowledge. Compared with low risk group, high risk group had a higher demand of peer education, Internet/multimedia, anonymous counseling and other forms of sexual health education. The differences were significant. Conclusion: The characteristics, sexual knowledge awareness, attitude and behavior, and health education demands of young students in different groups are different, so health education materials and methods should be developed according to the characteristics of different groups to enhance the acceptance and enthusiasm of students and improve the quality of sexual health education.

[Analysis on influencing factors of HIV testing services utilization in students with self-assessed high risk of HIV infection based on Andersen's model].

Objective: To analyze the influencing factors for HIV testing services utilization in students with self-assessed high risk of HIV infection. Methods: The research framework of the influencing factors for HIV testing services utilization in students was developed based on Andersen's health services utilization behavioral model and related literature. A cross-sectional survey was performed in students with self-assessed high risk of HIV infection by an online HIV infection risk assessment tool from March to April 2019. Multiple logistic regressions were applied with hierarchical model. Results: A total of 526 students were included in the study (age: 19.30±1.19 years old), in whom 96.2% agreed that HIV testing should be received after high-risk behavior. 56.7% (298/526) had sexual behavior and the HIV testing rate was 11.0% (58/526). The HIV testing rates in students who had and had no sex behavior were 13.42%(40/298) and 7.89% (18/228), respectively. According to the results from multivariate logistic regression analysis, non-heterosexual (compared with heterosexual, OR=7.88, 95%CI: 3.98-15.61) and higher score of AIDS knowledge awareness (compared with lower score, OR=2.05, 95%CI: 1.07-3.93) in propensity factor module, and having risk sexual behavior (compared with having no risk sexual behavior, OR=2.66, 95%CI: 1.41-5.03) and having diagnosis of STD infection in hospital (compared with having no such diagnosis, OR=6.35, 95%CI: 2.21-18.27) in demand factor module, and receiving health education about AIDS prevention in the past year (compared with receiving no such health education, OR=0.29, 95%CI: 0.11-0.76) and receiving health education about AIDS testing service in the past year (compared with receiving no such health education, OR=3.67, 95%CI: 1.71-7.90) in ability factor module were the influencing factors for utilization of HIV testing services. Conclusions: The acceptance of HIV testing in students needs to be improved urgently. Propensity factors, such as their AIDS knowledge awareness and sexual orientation, and demand factors, such as having risk sexual behavior and STD infection, have obvious impacts on the utilization of HIV testing services. However, health education about AIDS prevention and HIV testing service can play a more important role in facilitating the utilization of HIV testing in students. In the future, we should further strengthen the publicity of voluntary HIV counseling and testing service in students with particular attention to girls and those with risk sexual behaviors.