177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective:To investigate the application value and treatment opportunity of single balloon enteroscopy in children with Peutz-Jeghers syndrome(PJS).Methods:A retrospective analysis was conducted on 33 children diagnosed with PJS in Hunan Children′s Hospital from January 2011 to September 2021.The patient′s age, gender, family history, clinical symptoms, enteroscopy examination and treatment, number of polyps, intraoperative and pos-toperative complications, surgical treatment, recurrence of surgery, and follow-up data were analyzed, and the chi- square test was used for statistical analysis. Results:A total of 33 PJS children aged (9.00±3.13) years, including 21 males and 12 females, were included.All of them received at least once single balloon enteroscopy test.The main manifestations of the children were black spots (33 cases) and multiple polyps in the digestive tract (31 cases). In all the 33 cases, black spots were distributed on lips.Some black spots were also found at the end of fingers (3 cases), at the end of foot toes(2 cases), and at the end of finger toes (6 cases). During the operation, 391 polyps were removed, most of which were jejunum polyps (37.08%, 145/391 polyps). Eleven children with PJS has intussusception, of which intestinal intussusception accounted for 90.91% (10/11 cases). Ten cases (30.30%, 10/33 cases) received surgical treatment, and 72.73% (8/11 cases) underwent surgery for acute refractory intussusception.One case had intestinal perforation and 2 cases were bleeding during the operation, and the 3 cases recovered completely after hemostatic clip sealing and surgical treatment.The incidence of hollow ileum polyps and giant polyps in children aged >8 years was higher than that in children aged ≤8 years[92.55% (149/161 polyps) vs.7.45%(12/161 polyps), 96.20%(76/79 polyps) vs.3.80% (3/79 polyps)]. The differences were statistically significant ( χ2=9.854, 8.711, all P<0.05). There was no significant difference in the incidence of intussusception among different age groups ( P>0.05). Among the 33 children with PJS, 57.58% (19/33 cases) had recurrence 1-3 years after operation, and no cases of cancer have been followed up so far. Conclusions:Intestinal polyps are common in children with PJS, and the application of single-balloon enteroscopy in children with PJS is reliable and safe.Children over 8 years old are more vulnerable to empty ileum polyps and giant polyps.Therefore, it is advised that children aged above 8 years with PJS should undergo at least once enteroscopy.

Objective:To investigate the changes of CD8 + CD28 - regulatory T cells (Treg) and its role in the pathogenesis of Kawasaki disease (KD). Methods:A total of 48 children with KD were enrolled in the present study from June 2019 to December 2021. Blood samples were collected from them during acute phage of KD and after intravenous immunoglobulin (IVIG) treatment. Another 32 age-matched healthy children were recruited as control group. The proportions of CD8 + CD28 -Treg cells and the expression of programmed cell death protein 1 (PD-1), factor associated suicide ligand (FasL), inducible T-cell co-stimulator ligand (ICOSL), CD80 and CD86 protein were evaluated by flow cytometry. The expression of Helios, perforin, granzyme B, immunoglobulin-like transcript 3 (ILT3) and ILT4 at the transcription level was measured by real-time PCR. Concentrations of IL-10 and TGF-β in the culture supernatants of CD8 + CD28 -Treg cells stimulated with activated CD4 + T cells were measured by ELISA. Results:⑴ The proportions of CD8 + CD28 -Treg cells and the expression of Helios in patients with acute KD were higher than those in the control group ( P<0.05), and reduced remarkably after IVIG therapy ( P<0.05). The two afore-mentioned indexes were lower in patients combined with coronary artery lesion (CAL) than in those without coronary artery lesion (NCAL) ( P<0.05). ⑵ Compared with the control group, the patients with acute KD showed increased expression of FasL, PD-1, ICOSL and perforin in CD8 + CD28 -Treg cells ( P<0.05). The concentrations of IL-10 and TGF-β1 in the culture supernatants of CD8 + CD28 -Treg cells from patients with acute KD were lower than those in the control group after stimulation with activated CD4 + T cells ( P<0.05), which restored to some extent after IVIG treatment ( P<0.05). All of the six above-mentioned indexes in the CAL group were found to be lower than those in the NCAL group ( P<0.05). There were slight differences in granzyme B expression between different groups ( P>0.05). (3) In comparison with the healthy controls, the patients with acute KD showed overexpressed co-stimulatory molecules such as CD80 and CD86 on CD14 + cells ( P<0.05) and up-regulated expression of inhibitory molecules ILT3 and ILT4 ( P<0.05), which were restored remarkably after IVIG treatment ( P<0.05). Furthermore, the expression of CD80 and CD86 at protein level increased in the CAL group than in the NCAL group ( P<0.05), while the expression of ILT3 and ILT4 at transcriptional level decreased in the CAL group ( P<0.05). Conclusions:Relative insufficiency and impaired function of CD8 + CD28 -Treg cells might be one of the important factors resulting in immune dysfunction and vascular damage in KD patients.

Pace of life and work of people is accelerating nowadays, and hospitals keep improving their services, which gives rise to the decoction and delivery service from the third party vendors for traditional Chinese medicine(TCM).Given the quality control standards for the TCM decoction service as issued by Zhejiang and other regions, the systems of supervision and assessment remain incomplete.Authors of the paper introduced a project improvement team, composed of Chinese medicine pharmacy, Chinese medicine experience specialists, vendors of Chinese medicine decoction and express delivery companies, hence establishing a " three-in-one" supervision system of Internet+TCM decoction and delivery service. This practice can optimize the assessment indexes, strengthen the assessment system of assessment transformation and supervision system for patient medication.It proves that the practice contributes to higher quality and safety of TCM decoction and delivery service, improves the ability and level of TCM services, and ensures the medication safety of patients.

Objective To investigate the cliuical phenotype and the genotype of forty-one patients with steroid 5α-reductase type 2 deficiency.Methods The clinical data were collected including physical examination,medical history,laboratory test,as well as ultrasonic examination.Genomic DNA was extracted from peripheral blood leukocytes.Sanger sequencing and targeted gene captured next-generation sequencing were applied to detect the SRDSA2 gene mutation.Results All the patients are Han nationality and their ages ranged from 4 months to 11 years old.The karyotypes of 41 patients were 46,XY and all SRY genes were detected as positive.There were 26 (63％) patients manifested isolated micropenis,and the rest of fifteen patients were hypospadias associated with microphallus accounting for 37％.There were 39 patients who carried biallelic mutation.Two cases just identified one allele mutation.Sixteen gene mutation types were confirmed.Among them c.725A ＞ G (p.Tyr242Cys),c.694C ＞ G (p.His232Asp),and c.548-9T＞G are the novel gene types.The allele frequency of c.680G＞A (p.Arg227Gln) is 60％ (48/80).Conclusion The primary manifestations of patients with steroid 5α-reductase type 2 deficiency were micropenis or hypospadias accompanied with micropenis.c.680G＞A (p.Arg227Gln) is the predominantly mutation type of Chinese patient with steroid 5α-reductase type 2 deficiency.

Objective To investigate the clinical and biochemical metabolic features of 12 patients with systemic primary carnitine deficiency(CDSP) and to identify the SLC22A5 gene mutation types of the disease. Method The clinical and biochemical data were collected by retrospective analysis. DNA direct sequencing and multiplex ligation dependent probe amplification(MLPA)were applied for SLC22A5 gene analysis. Result Among 12 patients with CDSP, 3 cases had evident infection factors, 6 cases with convulsions, 5 cases manifested liver hypertrophy, 8 cases with hyperammonemia, and 9 cases showed myocardial damage. All CDSP patients were detected biallelic pathogenic mutation in SLC22A5 gene by direct sequencing. The gene types include IVS2+1G>T, c.3G>T(p.Met1Ile), c.760C>T(p.Arg254X), c.1400C>G(p.Ser467Cys), c.844dupc(p.Arg282fs), c.338G>A(p.Cys113Tyr), c.51C>G(p.Phe17Leu), c.659A>T(p.Glu220Val), and c.1365dupC(p.Thr456fs). c.659A>T(p.Glu220Val) and c.1365dupC(p.Thr456fs)are novel mutations. One female patient was maternal CDSP, her child had abnormal newborn screening. The allele frequency of c.760C>T(p.Arg254X) and c.1400C>G(p.Ser467Cys) were 37.5%(9/24)and 29.2%(7/24)respectively. The MLPA test results of all patients were negative. Conclusion The clinical manifestations are complex and various in patients with CDSP. Point and small InDel(insertions/deletions)mutation constitute the major alteration in SLC22A5 gene. c.1400C>G(p.Ser467Cys) might be another prevalence mutation type in Chinese CDSP patient.

OBJECTIVETo investigate the clinical phenotype and ACAT1 gene mutation in a family affected with beta-ketothiolase deficiency (BKTD).

METHODSClinical features and laboratory test data were collected. The probands were monozygotic twin brothers. Genomic DNA was isolated from peripheral blood leukocytes obtained from the probands and their family members. Molecular genetic testing of the ACAT1 gene was carried out.

RESULTSThe probands have presented with fever, vomiting and severe ketoacidosis. By arterial blood gas testing, pH was determined to be 7.164, bicarbonate was 4.0 mmol/L, and urine ketone was ++++. Urinary organic acid gas chromatography-mass spectrometry analysis showed excessive excretion of 3-hydroxybutyric acid, 2-methyl-3-hydroxybutyric acid and tiglylglycine. Increased 3-hydroxybutyrylcarnitine (C4-OH), tiglylcarnitine(C5:1) and 3-hydroxyisovalerylcarnitine (C5-OH) levels. The clinical phenotype of proband's parents were both normal, but an elder sister turned out to be an affected patient. Genetic analysis has identified two heterozygous mutations [c.622C>T(p.R208X) and c.653C>T (p.S218F)] in the proband, which were respectively detected in the mother and father. The c.653C>T (p.S218F) mutation was not found among the 100 healthy controls and has not been included in the Human Gene Mutation Database(HGMD).

CONCLUSIONThe primary clinical manifestations of BKTD is ketoacidosis. Urine organic acid and blood acylcarnitine analyses play an important role in the diagnosis of the disease. The compound heterozygous of ACAT1 gene mutations probably underlie the BKTD in our patient.

Acetyl-CoA C-Acetyltransferase ; genetics ; Acetyl-CoA C-Acyltransferase ; deficiency ; genetics ; Amino Acid Metabolism, Inborn Errors ; genetics ; Computational Biology ; Female ; Humans ; Infant ; Male ; Mutation ; Phenotype

Objective To estimate the radiation dose and cancer risk of thyroid for children who underwent head CT or chest CT scans.Methods The parameters used in the CT scans were accessed from the DICOM files through PACS used DCMTK software, then the thyroid radiation dose was estimated with the CT-Expo(C) software and the cancer risk induced by CT scan was projected based on BEIR Ⅱ model combined with the Chinese cancer incidence and lifetime table in 2008.Results CT parameters used for different ages were roughly the same, the thyroid equivalent dose for head CT ranged from 1.2-2.0 mGy, the highest thyroid cancer risk occurs for newborn girls, about 9.6/100 thousand population;while for chest CT the thyroid equivalent dose ranged from 8.1 to 38.0 mGy, the highest thyroid cancer risk was also for newborn girls, about 244.7/100 thousand population.The radiation dose and cancer risk for thyroid decreased with the increased age.Conclusions The radiation dose for thyroid from chest CT was relatively higher than head CT, especially for newborn babies;therefore more protection should be given to the thyroid and other radio-sensitive organs during CT scanning.

Objective To investigate the prevalence of physical state of HPV-l6 DNA in cervical cancer and cervical precancerous carcinoma. Methods Multiplex PCR was adopted to detect the physical state of HPV in samples from 252 patients with cervical carcinoma, including 48 samples of cervical cancer, 204 cervical intraepithelial neoplasia (CIN ) (125 CIN I, 46 CIN II and 33 CIN III) and 20 normal samples from the subjects with hysteromyoma undergoing hysterectomy, respectively. Results Among 48 patients with cervical cancer, 31 (65.6%) were infected with HPV-16. Eighteen among 31 (58.1%) HPV-16 infected patients with cervical cancer were found to have integrated infection of HPV-16. The positive rates of HPV-16 infection in the patients with CIN I, CIN II and CIN III were 19.2%, 34.8%and 42.4%, and the integrated infection rates of HPV-16 were 16.7%, 18.8%and 35.7%, respectively. Compared with patients with different grades of CIN, the integrated rate of HPV-16 infection in those with cervical cancer was significantly elevated. Conclusion Among the patients with HPV-16 infection, the integrated state of HPV-16 is positively correlated with the severity of cervical lesions. Combined HPV typing test and detection of integrated viral state contribute to predicting the prognosis of patients with cervical precancerous lesions and increasing the accuracy of screening cervical cancer on the basis of HPV DNA detection.

Objective To investigate the prevalence of physical state of HPV-l6 DNA in cervical cancer and cervical precancerous carcinoma. Methods Multiplex PCR was adopted to detect the physical state of HPV in samples from 252 patients with cervical carcinoma, including 48 samples of cervical cancer, 204 cervical intraepithelial neoplasia (CIN ) (125 CIN I, 46 CIN II and 33 CIN III) and 20 normal samples from the subjects with hysteromyoma undergoing hysterectomy, respectively. Results Among 48 patients with cervical cancer, 31 (65.6%) were infected with HPV-16. Eighteen among 31 (58.1%) HPV-16 infected patients with cervical cancer were found to have integrated infection of HPV-16. The positive rates of HPV-16 infection in the patients with CIN I, CIN II and CIN III were 19.2%, 34.8%and 42.4%, and the integrated infection rates of HPV-16 were 16.7%, 18.8%and 35.7%, respectively. Compared with patients with different grades of CIN, the integrated rate of HPV-16 infection in those with cervical cancer was significantly elevated. Conclusion Among the patients with HPV-16 infection, the integrated state of HPV-16 is positively correlated with the severity of cervical lesions. Combined HPV typing test and detection of integrated viral state contribute to predicting the prognosis of patients with cervical precancerous lesions and increasing the accuracy of screening cervical cancer on the basis of HPV DNA detection.