Objective Advances in synthetic DNA technology have made it much easier to fake human DNA samples.There are literature reports that fake human DNA can be synthesized by different methods and implanted in the field to confuse the investigation or mislead the trial.Therefore,distinguishing authentic human DNA from synthetic DNA and performing individual identification has become a critical scientific challenge.Methods We define a novel composite genetic marker(methylation-microhaplotype)by combining CpG sites stably hypermethylated or hypomethylated in natural human DNA and nearby immediately adjacent microhaplotype sites.A total of 19 locis were obtained according to the screening criteria,and a composite detection system for methylation-microhaplotypes was established using MPS technology.Random volunteer DNA samples were extracted and synthetic DNA samples were prepared based on whole genome amplification techniques.Population DNA samples were analyzed to evaluate forensic parameters and methylation variability of the methylation-microhaplotype markers.Comparative analyses of human and synthetic DNA were conducted to assess the markers'ability to discriminate between the two and to detect/type both components in mixed mixed samples.Results The composite detection system composed of 19 locis demonstrated high individual identification ability,achieving a cumulative individual identification probability of 0.999 999 999 996 86.12 hypermethylated locis and 7 hypomethylated locis had relatively stable methylation levels in 57 human DNA samples.According to the allele methylation rate(Ram)value,the system can effectively identify natural and synthetic DNA samples.Meanwhile,for mixed DNA samples,the presence of human and synthetic DNA samples can be found and genotyped.Conclusion Methylation-microhaplotype genetic markers,which can discover human DNA and synthetic DNA and can detect the presence and genotyping of them from mixed samples,is a potential useful tool for forensic DNA analysis.

Objective Advances in synthetic DNA technology have made it much easier to fake human DNA samples.There are literature reports that fake human DNA can be synthesized by different methods and implanted in the field to confuse the investigation or mislead the trial.Therefore,distinguishing authentic human DNA from synthetic DNA and performing individual identification has become a critical scientific challenge.Methods We define a novel composite genetic marker(methylation-microhaplotype)by combining CpG sites stably hypermethylated or hypomethylated in natural human DNA and nearby immediately adjacent microhaplotype sites.A total of 19 locis were obtained according to the screening criteria,and a composite detection system for methylation-microhaplotypes was established using MPS technology.Random volunteer DNA samples were extracted and synthetic DNA samples were prepared based on whole genome amplification techniques.Population DNA samples were analyzed to evaluate forensic parameters and methylation variability of the methylation-microhaplotype markers.Comparative analyses of human and synthetic DNA were conducted to assess the markers'ability to discriminate between the two and to detect/type both components in mixed mixed samples.Results The composite detection system composed of 19 locis demonstrated high individual identification ability,achieving a cumulative individual identification probability of 0.999 999 999 996 86.12 hypermethylated locis and 7 hypomethylated locis had relatively stable methylation levels in 57 human DNA samples.According to the allele methylation rate(Ram)value,the system can effectively identify natural and synthetic DNA samples.Meanwhile,for mixed DNA samples,the presence of human and synthetic DNA samples can be found and genotyped.Conclusion Methylation-microhaplotype genetic markers,which can discover human DNA and synthetic DNA and can detect the presence and genotyping of them from mixed samples,is a potential useful tool for forensic DNA analysis.

Osteosarcopenia is a geriatric syndrome referring to the co-existence of osteoporosis and sarcopenia.Its pathogenesis involves factors such as genetics, mechanics of the musculoskeletal system, endocrine regulatory mechanisms and molecular signaling pathways.In clinical practice, aside from comprehensive assessment of risk factors, screening of bone density, muscle strength, muscle mass and the overall body function must also be undertaken.Intervention measures primarily include therapeutic exercise, nutritional support and drugs.

OBJECTIVE To evaluate the quality and existing problems of Compound Paracetamol and Chlorphenamine Tablets for Infant. METHODS Using legal standards to inspect sampled samples, and several analytical methods were subsequently established or improved for the exploratory research on related substances, assay, dissolution, subdivision characteristics of scored tablets, and genotoxic impurities. RESULTS All samples met the regulatory specification, and the pass rate was 100%. However, the control for related substances was lacking, and the method for assay and content uniformity was defective. The exploratory studies showed that the assay and content uniformity met the requirements, and the risk of related substances and genotoxic impurities was acceptable. As a divisible tablet, the subdivision characteristics could not meet the requirements of the scored tablet, and the dissolution performance of some enterprise samples could not meet the requirements of similar products in foreign pharmacopoeias. CONCLUSION The overall quality of this product is adequate. However, due to the early time on the market, some quality attributes no longer meet the requirements of current regulations or relevant guidelines. The manufacturers should further optimize the prescription and production process, referring to foreign similar products. The current specification needs to be revised and improved.

Adenosine has been proved to have immunosuppressive effect in many different diseases, and the activity of ecto-5’-nucleotidase(CD73) on the cell surface is the rate-limiting step of extracellular adenosine production. CD73 has a profound and lasting impact on tumor immune regulation of regulatory T cells, B cells, macrophages and natural killer cells. CD73-mediated adenosine pathway is significant in signal transduction during cancer progression in tumor microenvironment, making CD73 a novel immune checkpoint. Therefore, CD73 inhibition is a emergent and promising strategy for cancer immunotherapy. At present, a variety of monoclonal antibodies and small molecule inhibitors have been in clinical development. This review comprehensively summarizes the frontier research progress of reported small molecule CD73 inhibitors, which can provide guidance for the investigation of novel CD73 inhibitors for cancer therapy.

Objective To investigate the incidence of neonatal hyperphenylalaninemia (HPA) and analyze the characteristics of HPA gene mutations in the Yangzhou area. Methods From January 2013 to December 2022, 285, 549 newborns in Yangzhou were screened for HPA using either the ninhydrin fluorescence method or tandem mass spectrometry. Urinary pterin analysis, erythrocyte dihydrobiopterin reductase activity measurement and genetic diagnosis were performed to screen positive individuals. Results A total of 29 cases were confirmed as HPA, including 3 cases of tetrahydrobiopterin (BH₄) deficiency and 26 cases of phenylalanine hydroxylase (PAH) deficiency. The overall incidence of HPA in Yangzhou was 1/9, 847, with the incidence of PAH deficiency being 1/10, 983, which were slightly higher than the national average but lower than other regions in Jiangsu Province. Among the cases, 13 (44.83%) were classic phenylketonuria (PKU), 7(24.14%) were mild PKU, and 6(20.69%) were mild HPA. Sixteen patients with PAH gene mutations were all compound heterozygotes, with one case exhibiting three-site mutations. PAH gene mutations were predominantly missense mutations, primarily concentrated in exon 7, followed by exon 6, with E7 c.728G>A (21.21%) being the most frequent mutation. Three cases of BH₄ deficiency were detected with PTS gene mutations, including 1 homozygous mutation and 2 compound heterozygous mutations. E5 c.259C>T was the high-frequency PTS mutation gene in Yangzhou. Conclusion HPA has a certain incidence in Yangzhou, with classic PKU being the predominant type. This study clarified the characteristics of PAH and PTS gene mutations in Yangzhou, enriching the HPA gene database.

Objective:To summarize the correlation between anterior pituitary function and tumor size in patients with different hormone-secreting pituitary adenomas.Methods:This was a retrospective case series study. The clinical data of 1 946 patients with pituitary adenoma hospitalized in the First Medical Center of Chinese PLA General Hospital from January 1, 2005, to December 31, 2020, were collected. The correlation between tumor size and anterior pituitary hormone levels was analyzed using Spearman rank correlation analysis in different types of pituitary adenomas.Results:The median age of the 1 946 patients was 45.1 years, of which 857 (44.0%) were men. The maximum tumor diameter of the patients [ M ( Q1, Q3)] was 22 (14, 30) mm. Tumor size in nonfunctioning adenomas ( n=1 191) was negatively correlated with adrenocorticotropic hormone (ACTH) ( r=-0.11, P<0.001), growth hormone ( r=-0.13, P<0.001), and luteinizing hormone (men: r=-0.26, P<0.001, women: r=-0.31, all P<0.001). The tumor size of somatotropic adenomas ( n=297) was positively correlated with growth hormone ( r=0.46, P<0.001), but negatively correlated with male testosterone ( r=-0.41, P<0.001). The tumor size of ACTH-secreting pituitary adenomas ( n=155) was positively correlated with the ACTH level at 8∶00 AM ( r=0.25, P<0.001); however, no correlation was found with cortisol at 8∶00 AM ( P>0.05). The tumor size of prolactinomas ( n=303) was positively correlated with the prolactin level (men: r=0.34, P=0.001; women: r=0.13, P=0.070). Conclusions:The correlation between the function of the anterior pituitary and size of the tumor depends on the cellular origin of the pituitary adenoma and specific type of hormone secretion. In somatotroph adenomas, ACTH-secreting pituitary adenomas, and prolactinomas, there is a positive correlation between tumor size and level of hormones secreted by the corresponding tumors. In patients with nonfunctioning adenomas, the tumor size was negatively correlated with the hormone levels of the pituitary-adrenal and pituitary-growth hormone axes.

Objective: To investigate the feasibility of using a carbon dioxide(CO2) laser in the treatment of facial papilloma in children and to evaluate its curative effect and prognosis. Methods : A case of pediatric facial papilloma treated with a CO2 laser was reported, and the effects of this disease and CO2 laser treatment were reviewed and analyzed in combination with the literature. Results: Under general anesthesia, the lesion tissue of the left lip was excised for pathological biopsy, and the diagnosis was maxillofacial papilloma. The lesions were surgically ablated in stages with a CO2 laser, and erythromycin ointment was applied to the surgical incision after surgery. A total of three rounds of CO2 laser treatment were performed for 3 treatment courses. The child had no complications during or after the operation, the facial appearance was significantly improved, and there was no sign of recurrence during the 6-month follow-up. A literature review showed that CO2 lasers have been widely used in the excision of various surface lesions. In clinical practice, continuous CO2 laser with power of 10-50 W and wavelength of 10.6 μm is used to treat superficial tissue lesions, which can achieve accurate vaporization resection of diseased tissue, less bleeding and a good prognosis. Conclusion CO2 laser was accurate and minimally invasive for the removal of facial papilloma in children.

Objective: To investigate the association of GNA11 gene polymorphisms with the risk of adult-onset non-surgical hypoparathyroidism (Ns-HypoPT). Methods: Genotyping of GNA11 single nucleotide polymorphisms (SNPs) (rs28685098, rs4806907, rs11084997 and rs78003011) was carried out in 203 patients and 209 healthy participants by sequenom MassArray iPLEX System. These SNPs are located in promoter and 3′untranslated region (3′UTR) of GNA11 gene, respectively. Results: Allele and genotype frequencies of rs11084997 in patients were significantly different from those of controls (genotype GG:60.5% vs. 49.8%, GC: 35.5% vs. 41.6%, CC: 4.0% vs. 8.6%, P=0.038; G allele 78.3% vs. 70.6%, C allele 21.7% vs. 29.4%, P=0.012), and the C allele of rs11084997 carriers had a lower risk to develops Ns-HypoPT in additive and dominant genetic models [OR=0.382 (0.160-0.915), 0.647 (0.437-0.957)]. CC-Haplotype formed by the minor alleles of rs4806907 and rs11084997 was associated with a decreased risk of Ns-HypoPT in additive, dominant and recessive genetic model [OR=0.317 (0.126-0.801), 0.640 (0.430-0.952), 0.367 (0.148-0.912)]. Conclusion The minor allele C of rs11084997 in GNA11 gene promoter was associated with decreased risk of Ns-HypoPT in Chinese population.

Objective To explore the appropriate target ranges of blood glucose in intensive insulin therapy (ⅡT) for acute hyperglycemia following traumatic brain injury (TBI).Methods A randomized,open-label and controlled clinical trial was performed on 208 patients,admitted to our hospitals from Junuary 2014 to Sepember 2016.They were divided into ⅡT group (n=156),who were subdivided into slight (10.1-13.0 mmol/L),moderate (7.1-10.0 mmol/L),and strict (4.4-7.0 mmol/L) control blood glucose groups (n=52),and non-ⅡT group (n=52).Survival analysis 6 months after treatment was performed by Kaplan-Meier method.Modified Rankin scale (mRS) scores and Barthel index (BI),Glasgow Outcome scale (GOS) scores,concentrations of lactic acid in cerebrospinal fluid (CSF) and glycosylated hemoglobin,Glasgow coma scale (GCS) scores,Acute Physiology and Chronic Health Evaluation (APACHE Ⅱ) scores,Length of staying in intensive care unit (ICU) and incidence of adverse events were compared between the patients from different groups at different treatment times.Results Blood glucose level within 7 d of admission in patients ofⅡT group was in target ranges.The survival rate of patients from slight and moderate control blood glucose groups was significantly higher than that in the non-ⅡT group and strict control blood glucose group 6 months after treatment (x2=4.237,P=0.040;x2=5.621,P=0.018).As compared with those in the non-ⅡT group and strict control blood glucose group,the mRS scores 3 months after treatment were significantly decreased,and GOS scores and BI one,3 and 6 months after treatment were significantly increased in patients from slight and moderate control blood glucose groups (P＜0.05).As compared with that in the non-ⅡT group,and slight and moderate control blood glucose groups,the glycosylated hemoglobin level 7 d after treatment was significantly decreased in strict control blood glucose group (P＜0.05).As compared with those in the non-ⅡT group and strict control blood glucose group,the concentration of lactic acid in CSF 7 d after treatment,APACHE Ⅱ scores 7 and 14 d after treatment,length of staying in ICU and incidence of adverse events were significantly decreased in patients from slight and moderate control blood glucose groups (P＜0.05).The mean value of blood glucose in slight and moderate control blood glucose groups was (8.40±0.39) mmol/L.Conclusion Proper ⅡT improves the outcomes of TBI patients and (8.40±0.39) mmol/L are established as the target ranges in ⅡT for TBI.