Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

Objective:To analyze the monitoring results of iodine deficiency disorders in Nanning City in 2020, learn about the consumption of iodized salt among residents and the iodine nutrition status of key populations, and provide scientific basis for formulating or adjusting targeted prevention and control measures of iodine deficiency disorders.Methods:According to the Guangxi Iodine Deficiency Disorders Monitoring Plan, monitoring was carried out in all of 12 districts (counties) in Nanning City. One township (street) was selected from each of the five directions of east, west, south, north, and central. Forty non-boarding children aged 8 to 10 and 20 pregnant women were selected as monitoring subjects in each township (street). Edible salt samples were collected from children and pregnant women to detect salt iodine content, random mid-course urine samples from children and morning urine samples from pregnant women were collected to detect urinary iodine content; in addition, thyroid examination of children was conducted in Qingxiu District, Liangqing District, Long an County and Shanglin County.Results:In 2020, a total of 2 434 children aged 8 to 10 and 1 207 pregnant women were surveyed in Nanning City. The coverage rate of iodized salt, the qualified rate of iodized salt and the qualified iodine salt consumption rate were 99.67%(3 629/3 641), 97.99%(3 556/3 629) and 97.67%(3 556/3 641), respectively. The median urinary iodine of children was 182.0 μg/L, and the median values ranged from 146.5 to 234.8 μg/L in different districts (counties), there were significant differences in median urinary iodine between urban and non-urban areas, different gender and age groups ( U = 2.38, 2.41, P = 0.017, 0.016; H = 16.42, P < 0.001). The goiter rate of children was 0.99%(8/807), and the rate ranged from 0 to 2.00% (4/200) in the 4 districts (counties) examined, there were significant differences in thyroid volume between urban and non-urban areas and different ages ( U = - 3.52, P < 0.001; H = 47.67, P < 0.001). The median urinary iodine of pregnant women was 191.0 μg/L. The median urinary iodine of different districts (counties) ranged from 141.0 to 241.5 μg/L, and the difference was statistically significant at different gestational stages ( H = 24.37, P < 0.001). Conclusion:In 2020, the coverage rate of iodized salt, the qualified rate of iodized salt and the qualified iodine salt consumption rate by residents in Nanning City are high, and the iodine nutrition of both children and pregnant women are at an appropriate level.

ObjectiveCOVID-19 vaccination is critical for pandemic control， especially in the elderly. Compared with developed countries， the rate of full vaccination and booster vaccination for the elderly in China is low， making it urgent to accelerate the process of vaccination for the elderly in China. MethodsThis study summarizes the policy experiences of the United Kingdom， the United States， Singapore， and South Korea by sorting relevant literature and government websites， analyzes the current performance and reasons for COVID-19 vaccination among the elderly in China， and explores strategic suggestions for improving COVID-19 vaccination in the elderly in terms of vaccination priority groups， service provision， and vaccination intention. ResultsIt is important to vaccination rate for the elderly in China by focusing on the priority vaccination population， establishing a permanent mechanism based on the family doctor system， and increasing the willingness to vaccinate. ConclusionContinued reinforcement of COVID-19 vaccination for the elderly is needed， and the existing vaccination model is overwhelming. We should establish a permanent mechanism based on the family doctor system to transfer from a mobilization model to a regular vaccination model.

Objective To determine the serum IgM and IgG antibody levels post-COVID-19 vaccination， and provide scientific evidence for COVID-19 antibody response after vaccination. Methods A total of 980 healthy persons were included in Kunming Third People’s Hospital from July through August， 2021， which had been vaccinated with COVID-19 vaccines and then tested for anti-SARS-CoV-2 IgM and IgG antibodies. Results After the COVID-19 vaccination， 469 persons （positive rate， 47.86%） were positive for anti-IgG antibody. Of them， 75 were males with （positive rate， 39.06%）， and the average IgG level was 0.618 （0.180， 2.526） AU·mL^-1［M（Q₁，Q₃）］； 394 were females （50.00%）， and the IgG level was 0.999 （0.305， 3.334） AU·mL^-1. In addition， 53 persons （5.41%） were anti-IgM antibody positive. Of them， 14 were males （positive rate， 7.29%）， and the average IgM level was 0.057 （0.026， 0.195） AU·mL^-1； 39 were females （4.95%）， and the IgM level was 0.047 （0.027， 0.110） AU·mL^-1. The positive rate of anti-IgG antibody was highest in those aged ≤30 years， which was 51.02% in male （n=25） and 55.88% in female （n=133）. The anti-IgG response differed significantly by gender （χ²=7.401， D=0.135 1， P<0.05）， whereas the anti-IgM response was not significantly different （χ²=1.656， P>0.05）. Among the age groups， anti-IgG antibody level was higher in those aged ≤30 and 51-70 years， with 158 （55.05%） and 122 （52.36%） persons， respectively； the average antibody level was 1.209 （0.426， 4.386） AU·mL^-1 and 1.074 （0.191， 7.670） AU·mL^-1， respectively. The differences in the positive rates of IgG and IgM antibodies and the levels of IgG antibodies among different age groups were statistically significant （P<0.05）. Using Kruskal-Wallis test and Spearman correlation analysis， it showed a high correlation between the IgG and IgM antibodies （r=0.836 4， H=64.82， 20.09， P<0.05）. Conclusion The Anti-SARS-CoV-2 IgG antibody remains high six months post-COVID-19 vaccination， while anti-IgM antibody is low. The IgM and IgG response are higher in the young and elderly. The response differs by gender and age， demonstrating a correlation.

Haloacetaldehydes (HALs), as emerging disinfection by-products in drinking water, are the third largest group by weight of identified disinfection by-products (DBPs) in drinking water. The formation of HALs is associated with the level of natural organic matter and halide in the source water, the treatment process of drinking water and the type of disinfectant. Recent studies have shown that HALs are more cytotoxic and genotoxic than regulated trihalomethanes and halo-acetic acids in drinking water. Currently, only a few countries and regions have set limit values for trichloroacetaldehyde with high detection rate in drinking water. However, there is growing evidence that unregulated HALs have a higher potential risk to human health compared to regulated HALs. This paper reviews the current research progress on the formation and transformation, cytotoxicity and genotoxicity of HALs in drinking water, and looks forward to the problems that should be paid attention in the future toxicological research of HALs in order to support the development of scientific drinking water standards.

Haloacetaldehydes (HALs), as emerging disinfection by-products in drinking water, are the third largest group by weight of identified disinfection by-products (DBPs) in drinking water. The formation of HALs is associated with the level of natural organic matter and halide in the source water, the treatment process of drinking water and the type of disinfectant. Recent studies have shown that HALs are more cytotoxic and genotoxic than regulated trihalomethanes and halo-acetic acids in drinking water. Currently, only a few countries and regions have set limit values for trichloroacetaldehyde with high detection rate in drinking water. However, there is growing evidence that unregulated HALs have a higher potential risk to human health compared to regulated HALs. This paper reviews the current research progress on the formation and transformation, cytotoxicity and genotoxicity of HALs in drinking water, and looks forward to the problems that should be paid attention in the future toxicological research of HALs in order to support the development of scientific drinking water standards.

Objective    To define the patient characteristics and perioperative management, and to define the mortality and its risk factors after arterial switch operation (ASO). Methods    We conducted a bidirectional cohort study with 571 consecutive patients undergoing ASO from 1997 to 2016 in our hospital. We enrolled patients who underwent ASO before 2012 retrospectively and after 2012 prospectively and followed up all the patients prospectively. Demographic characteristics, clinical information and mortality of these patients were summarized. Joinpoint regression analysis was used to identify the time trend of the overall mortality. Kaplan-Meier survival analysis was used to evaluate the mid- and long-term survival rate after ASO. Cox proportional hazards regression models were used to explore the potential factors associated with mortality. The cumulative incidence of complications after ASO was predicted using competing risk models. Results    Several aspects of patients’ characteristics and perioperative management in our center differed from those in the developed countries. The overall mortality and in-hospital mortality after ASO was 16.3% and 15.1%, respectively. The overall cumulative survival rate at 5, 10 and 15 years after ASO was 83.3%, 82.8% and 82.8%, respectively. A significant decrease of overall mortality from 1997 to 2016 was observed. Independent risk factors of mortality included earlier ASO (1997-2006), single or intramural coronary anatomy and longer cardiopulmonary bypass time. Ten years after ASO, re-intervention, arrhythmia, pulmonary and anastomotic stenosis were the most common complications with a cumulative incidence over 10%. Conclusion    Significant improvements in the results of the ASO were observed and the postoperative mortality rate is close to reports from developed countries. Nonetheless, we have identified the need for further improvement in the early and late postoperative periods after ASO. Pulmonary stenosis, anastomotic stenosis and arrhythmia should be paid attention to during the long-term follow-up after ASO.

Objective To explore the clinical effect of endoscope assisted suction-cutter removal of apocrine sweat glands in treatment of osmidrosis.Methods This study generalized and analyzed the curative effects of 30 patients with axillary osmidrosis,treated with endoscopy assisted suction-cutter removal of apocrine sweat glands.The efficacy was evaluated according to the postoperative results and complications.Results In all the 30 patients,wound healed 7 to 10 days after operation,and they resumed almost normal life after treatment.From May 2015 to April 2017,the follow-up visits showed that none of them had relapse,infection or skin necrosis.Surgical scar was slight,and in all the patients,symptoms disappeared.Conclusions The operation of endoscopy assisted suction-cutter removal of apocrine sweat glands is a minimally invasive surgery.The advantages include direct vision,radical operation,well preserved dermal vascular network and lower risk of complications.

Objective To explore the effect of the surgical treatment in neonates with congenital heart disease(CHD) and the factors related to the perioperative mortality during cardiopulmonary bypass. Methods Totally,666 neonates undergo-ing CHD operation were reviewed in a single center from Jan 2006 to Dec 2014,of which,431 cases had complete cardiopul-monary bypass records. Analysis was performed to investigate the association between perioperative mortality and potential fac-tors,especially the cardiopulmonary bypass factors during different periods. In the multivariate Cox proportional hazard model, factors with statistical significance(P < 0. 1)in the univariate analysis were included in the model,such as,surgeon grouping, year of surgery,Aristotle score,preoperative weight,preoperative and intraoperative sodium bicarbonate volume and postopera-tive low cardiac output. Results The neonates enrolled ranged 8 - 22 days after birth,and 2. 7 - 3. 6 kg at weight. The mor-tality rate decreased from 23. 7％ in 2006 to 12. 4％ in 2014,showing a gradual decline(P = 0. 02). The mortalities of differ-ent CHDs were:pulmonary atresia(24. 4％),coarctation of the aorta( 16. 7％),transposition of the great arteries( 13. 1％), total anomalous pulmonary venous connection( 11. 0％),ventricular septal defect( 10. 6％),and so on. The volume of preop-erative and intraoperative 5％ sodium bicarbonate was 30(20 - 50)mL in death group,higher than that in survival group[23 ( 15 - 30)ml]. While the preoperative weight was 3. 1(2. 7 - 3. 5)kg,lower than that in survival group[3. 3(3. 0 - 3. 6) kg]. The total amount of Plasmalyte/ Ringer,erythrocytes,ultrafiltration volume and the cardiac assist ratio were higher in the death group than in the survival group. After controlling the confounding effect of surgeons,the multivariable Cox proportional hazard model showed that:the independent risk factors for perioperative mortality were pulmonary atresia[aHR = 3. 89( 1. 78 -8. 42)],5％ sodium bicarbonate volume ≥50 ml[aHR = 2. 62( 1. 14 - 6. 04)],erythrocytes volume > 200 ml[aHR = 2. 26 ( 1. 1 - 4. 06)]and postoperative low cardiac output[aHR = 6. 76(3. 30 - 13. 87)]. Conclusion During the study period, the preoperative mortality for neonates with CHD had a dramatical decrease,although the preoperative risk factors for the pa-tients increased. Pulmonary atresia repair surgery had the highest mortality in neonates. Factors associated with the periopera-tive mortality includedpreoperative acidosis and postoperative low cardiac output. There is a significant association between the improvement of perioperative mortality and the improvement of the technology of minimized cardiopulmonary bypass circuit dur-ing neonatal operation. It is suggested that the total erythrocytes volume maintains less than 200 ml.

[Objective]To evaluate the effects of sutureless technique in comparison to conventional techniques for repair of total anomalous pulmonary venous connection(TAPVC)with the method of propensity score analysis.[Methods]From October 2007 to December 2013,179 consecutive patients were enrolled in this study. Patients were operated with sutureless technique(n = 81)or Conventional technique(n=98),and followed up at an interval of 1 month,3 months,6 months and then once a year post-operation. During analysis,three type of propensity-score matching methods,including nearest neighbor caliper matching,Mahalanobis metric matching with propensity score ,optimal full matching were used to create balanced groups of patients receiving each treatment. Surgeons’performance difference was assessed with random frailty proportional hazards models with gamma. Composite endpoints was defined by postoperative death or late death or postoperative pulmonary venous obstruction(PVO),which was evaluated with Kaplan-Meier curve and multivariable Cox proportional hazard model,adjusted by Preoperative-PVO,age,gender,weight and TAPVC type.[Results]Nearest neighbor caliper matching method was the best choice during propensity score analysis. After matching ,sutureless group included 73 patients and Conventional group73 patients. In sutureless group,cardiopulmonary bypass(CPB)time(Z=2.18, P=0.030),cross-clamp time(Z=3.63,P<0.001),rate of composite endpoints(HR 95%CI=0.20(0.06~0.61),P=0.005),late death(HR 95%CI=0.03(0.01~0.55),P=0.017)were significantly better than that in Conventional group. In subgroup analysis ,for patients with pre-PVO,decreased composite endpoints was seen in sutureless group.[Conclusion]Comparison using thepropensity score analysis demonstrated that sutureless strategy for primary repair of TAPVC may associate with decreased mortality rate of post-PVO and CPB time and cross-clamp time.