Objective To assess the impact of the virus on the complementary determining region 3 (CDR3) length diversity of T cell receptor(TCR) Vβ repertoires of CD4+ T lymphocytes and to explore its association with viral load in individuals with HIV-1 infection. Methods The TCR repertoire was examined using spectratyping of CDR3 length diversity within CD4+ T cells in HIV infected and healthy adults. Separation of CD4+ T cells from peripheral blood mononuclear cells ( PBMCs) was carried out by using immunomagnetic beads coated with anti-CD4 antibody. Total RNAs from the purified CD4 + T lymphocytes were isolated and used to perform nested-PCR amplifications in CDR3 of 22 TCR gene families. CDR3 diversity and its association with viral load in individuals with HIV-1 infection were analyzed. Results An average diversity for all CDR3 profiles in CD4+ T cells from 25 HIV-infected individuals was significantly different as compared to 10 age-matched healthy donors (P＜0.05) with the HIV-infected individuals losing diversity in the CDR3 profiles. There was positive correlation between changes in TCR CDR3 diversity and viral load (r = 0. 494, P ＜ 0. 05). The changes in CDR3 length diversity of Vβ families in HIV-infected individuals, particular in Vβ8, Vβ22, Vβ23 were statistically different from the healthy controls. Conclusion HIV-1 infection might induce the loss of TCR Vp repertoire diversity and disrupt the CDR3 Gaussian distributions within CD4 + T cells. There should be positive correlation between changes in TCR CDR3 diversity and the viral load in HIV-1 infected patients.

Objective: To explore whether PIK3R3 is dependent on PPARA to regulate fat metabolism and proliferation of liver cancer cells. Methods: The PIK3R3 overexpression plasmids and its specific siRNA were transfected into hepatocellular carcinoma cells HepG2 and SMMC-7721. The level of PPARA was detected by Western blotting（WB）and the ketone body content in supernatant was measured by colorimetric method.DNA synthesis and proliferation of hepatocellular carcinoma cells were detected by BrdU/PI incorporation method and CCK8 method. Then we used PIK3R3 overexpression or silenced hepatocellular carcinoma cell lines to observe the effect of PIK3R3 on the proliferation of hepatocellular carcinoma cells by plate cloning experiments. We intervened the expression of PIK3R3 and then observed the lipid metabolism and cell proliferation，so as to determine whether the role of PIK3R3 in hepatocellular carcinoma cells depends on PPARA. Finally, we added MG132（proteasome inhibitor）or CHX（cycloheximide）to PIK3R3 overexpression or silencing hepatocellular carcinoma cells to detect the level of PPARA by WB，next we constructed the plasmids of PPARA promoter luciferases and observed the effect of PIK3R3 on the activity of PPARA promoter. Results: PIK3R3 influenced the expression of PPARA，lipid metabolism and proliferation of hepatocellular carcinoma cells，and PPARA partly reversed the effects of PIK3R3. Conclusion PIK3R3 can regulate the fat metabolism and proliferation of hepatoma cells by regulating the expression of PPARA.

Objective To investigate the potential active ingredients and the mechanism of Coreopsis tinctoria Nutt. in the prevention and treatment of hyperlipidemia. Methods Ultra-high performance liquid chromatography-Quadrupole-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap MS) was used to qualitatively analyze the fractions and blood components of flavones in Coreopsis tinctoria Nutt. The intersection targets of flavones in Coreopsis tinctoria Nutt. and hyperlipidemia were screened,and the protein-protein interaction network was constructed and analyzed by the STRING 12.0 database. Finally,the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for enrichment analysis. Results A total of 25 compounds were detected from the flavones in Coreopsis tinctoria Nutt.,and their structures were identified,including ten chalcones,nine flavanones,four flavonols,one aurone,and one biflavone. The analysis of blood components showed that marein,flavanomarein,okanin,isookanin and 5,7,3',5'-tetrahydroxyflavanone-7-O-β-D-glucopyranoside were the main components of the flavones in Coreopsis tinctoria Nutt. in blood. Network pharmacological GO and KEGG enrichment analysis showed that the flavones in Coreopsis tinctoria Nutt. may regulate phosphatidylinositol 3-kinase/protein kinase B,tumor necrosis factor,hypoxia-inducible factor-1 signaling pathway and other signaling pathways in the regulation and prevention of hyperlipidemia. Conclusion Coreopsis tinctoria Nutt. can prevent and treat hyperlipidemia,and the mechanism may be related to the five blood components of the flavones in Coreopsis tinctoria Nutt.,including marein,flavanomarein,okanin,isookanin and 5,7,3',5'-tetrahydroxyflavanone-7-O-β-D-glucopyranoside.

Objective:This study aims to explore the temporal trend of Low Anterior Resection Syndrome (LARS) and its symptoms after laparoscopic anterior resection for rectal cancer.Methods:A retrospective cohort study design was employed. The study included primary rectal (adenocarcinoma) cancer patients who underwent laparoscopic anterior resection at Tongji Hospital, Huazhong University of Science and Technology, between January 1, 2010, and December 31, 2020. Complete medical records and follow-up data at 3, 6, 9, 12, and 18 months postoperatively were available for all patients. A total of 1454 patients were included, of whom 1094 (75.2%) were aged ≤65 years, and 597 (41.1%) were females. Among them, 1040 cases (71.5%) had an anastomosis-to-anus distance of 0-5cm, and 86 cases (5.9%) received neoadjuvant treatment. All patients completed the Chinese version of the LARS questionnaire and their LARS occurrence and specific symptom information were recorded at 3, 6, 9, 12, and 18 months postoperatively. Considering past literature and clinical experience, further subgroup analyses were performed to explore the potential impact factors on severe LARS, including anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma.Results:The occurrence rates of LARS at 3, 6, 9, 12, and 18 months postoperatively were 78.5% (1142/1454), 71.4% (1038/1454), 55.0% (799/1454), 45.7% (664/1454), and 45.7% (664/1454), respectively (χ 2=546.180 , P<0.001). No statistically significant difference was observed between the 12-month and 18-month time points ( P>0.05). When compared with the symptoms at 3 months, the occurrence rates of gas incontinence [1.7% (24/1454) vs. 33.9% (493/1454)], liquid stool incontinence [3.9% (56/1454) vs. 41.9% (609/1454)], increased stool frequency [79.6% (1158/1454) vs. 95.9% (1395/1454)], stool clustering [74.3% (1081/1454) vs. 92.9% (1351/1454)], and stool urgency [46.5% (676/1454) vs. 78.7% (1144/1454)] in the LARS symptom spectrum were significantly alleviated at 12 months (all P<0.05) and remained stable beyond 12 months (all P>0.05). With the extension of postoperative time, the incidence rates of severe LARS exhibited a decreasing trend in different subgroups, of anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma, and reached stability at 12 months postoperatively (all P>0.05). Conclusion:LARS and its specific symptom profile showed a trend of gradual improvement over time up to 1 year postoperatively, and stabilized after more than 1 year. Increased stool frequency and stool clustering are the most common features of abnormal bowel dys function, which improve slowly after surgery.

Objective:This study aims to explore the temporal trend of Low Anterior Resection Syndrome (LARS) and its symptoms after laparoscopic anterior resection for rectal cancer.Methods:A retrospective cohort study design was employed. The study included primary rectal (adenocarcinoma) cancer patients who underwent laparoscopic anterior resection at Tongji Hospital, Huazhong University of Science and Technology, between January 1, 2010, and December 31, 2020. Complete medical records and follow-up data at 3, 6, 9, 12, and 18 months postoperatively were available for all patients. A total of 1454 patients were included, of whom 1094 (75.2%) were aged ≤65 years, and 597 (41.1%) were females. Among them, 1040 cases (71.5%) had an anastomosis-to-anus distance of 0-5cm, and 86 cases (5.9%) received neoadjuvant treatment. All patients completed the Chinese version of the LARS questionnaire and their LARS occurrence and specific symptom information were recorded at 3, 6, 9, 12, and 18 months postoperatively. Considering past literature and clinical experience, further subgroup analyses were performed to explore the potential impact factors on severe LARS, including anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma.Results:The occurrence rates of LARS at 3, 6, 9, 12, and 18 months postoperatively were 78.5% (1142/1454), 71.4% (1038/1454), 55.0% (799/1454), 45.7% (664/1454), and 45.7% (664/1454), respectively (χ 2=546.180 , P<0.001). No statistically significant difference was observed between the 12-month and 18-month time points ( P>0.05). When compared with the symptoms at 3 months, the occurrence rates of gas incontinence [1.7% (24/1454) vs. 33.9% (493/1454)], liquid stool incontinence [3.9% (56/1454) vs. 41.9% (609/1454)], increased stool frequency [79.6% (1158/1454) vs. 95.9% (1395/1454)], stool clustering [74.3% (1081/1454) vs. 92.9% (1351/1454)], and stool urgency [46.5% (676/1454) vs. 78.7% (1144/1454)] in the LARS symptom spectrum were significantly alleviated at 12 months (all P<0.05) and remained stable beyond 12 months (all P>0.05). With the extension of postoperative time, the incidence rates of severe LARS exhibited a decreasing trend in different subgroups, of anastomosis level, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and the presence of preventive stoma, and reached stability at 12 months postoperatively (all P>0.05). Conclusion:LARS and its specific symptom profile showed a trend of gradual improvement over time up to 1 year postoperatively, and stabilized after more than 1 year. Increased stool frequency and stool clustering are the most common features of abnormal bowel dys function, which improve slowly after surgery.

Objective:To analyze the trend of liver cancer morbidity and mortality among residents with household registration in certain District, 2017 to 2019.Methods:The crude morbidity and mortality rate of males and females in the whole population were calculated by using the relevant data from the certain District Cancer Registry and Report System and the Cause of Death Surveillance System. The standardized morbidity and mortality rate were calculated according to the age structure of 2000 National Demographic Census and Segi's world population, respectively. Trend in liver cancer morbidity and mortality were evaluated using percent change (PC), annual percentage change, and case-number-weighted annual percent change. Age-specific rates were used to analyze the epidemic trend of liver cancer with age.Results:The crude morbidity rate of liver cancer in the whole population (male and female) of the certain district from 2017 to 2019 were 18.86/100 000, 26.05/100 000 and 11.90/100 000 respectively, and the crude mortality rates were 21.20/100 000, 29.29/100 000 and 13.38/100 000 respectively. The crude morbidity and mortality rate of liver cancer among male showed a downward trend (PC=-16.77% and -20.15% respectively). The crude morbidity and mortality rate of liver cancer among female showed inconsistent changes; however, the crude morbidity rate showed a downward trend, and the crude mortality rate first increased and then decreased (PC=-19.42% and -0.30% respectively). Liver cancer morbidity and mortality rate in male after the age of 30 were increased with age. The two key points of accelerated growth were around the age of 65 and 75, and the peak of morbidity (130.78/100 000) and mortality (201.96/100 000) were after the age of 80. The morbidity and mortality rate were significantly lower in female than those of male aged 60; however, after the age of 65, the morbidity rate was increased rapidly and gradually approached as that of male. After the age of 80 (the peak morbidity and mortality were 104.40/100,000 and 132.87/100,000, respectively), male were about twice as high as those female aged between 75 and 79.Conclusion:Morbidity and mortality rate of liver cancer in the certain District showed an overall downward trend from 2017 to 2019, but it increased with age, and the disease burden was relatively high among the elderly population. Liver cancer mostly occurred in male, so the prevention and control of liver cancer epidemics in middle-aged and elderly should be actively monitored.

The terminal ileostomy is an important surgical procedure for reducing the severity of anastomotic leakage(AL)and serious postoperative complications in rectal cancer surgery.The decision of terminal ileostomy is related to the subjective judgment of surgeons and the risk of AL,however,due to the lack of objective clinical guidelines,the decision of terminal ileostomy mainly relies on the surgeons'experience.A large number of researches have developed or proposed some tools,such as scoring models,Nomogram,expert consensus,clinical guidelines,and artificial intelligence(AI)models,are dedicated to predicting postoperative AL or making reasonable decisions for the implementation of terminal ileostomy.Although some studies have shown favorable expected results,there is still a lack of high-quality data validation.At present,the rational implementation of decision-making for terminal ileostomy is still being explored.It is believable that the personalized implementation of terminal ileostomy can be achieved in the near future with the development of new technologies for intraoperative anastomosis detection and the advancement of high-quality clinical big data research.

OBJECTIVE: To investigate the gene mutation types and spectrum of α, β-thalassemia in Fuzhou area of China. METHODS: Thalassemia gene screening was performed in the women receiving physical, prenatal, and pre-pregnancy examination, and the patients with suspected thalassemia in our hospital from July 2013 to March 2018.Genotypes of thalassem were detected by Gap-PCR and RDB-PCR. RESULTS: 1042 were positive among 2074 suspected cases with a positive rate of 50.24%; 618 cases were confirmed to be α-thalassemia and with a positive rate of 29.8%; 409 cases were confirmed to be β-thalassemia with a positive rate of 19.72%. 15 cases were confirmed to be α-β complex thalassemia with a positive rate of 0.72%. the --/αα(76.54%) was the most common genotype among α-thalassemia, -α/αα(10.03%) and -α/αα(2.91%) in hot pursuit. In addition, IVS-II-55 (T->G) and IVS-II-119 (-G, +CTCGGCCC) were newly found alpha mutations; the IVS-2-654 (C→T) (40.83%) was the most common genotype among β-thalassemia, CD41-42 (-TCTT) (35.94%) and CD17 (A→T) (9.78%) in hot pursuit. CONCLUSION The genotype of thalassemia in Fuzhou area is highly heterogenic, --/αα is the most common genotype among α-thalassemia, IVS-2-654 (C→T) is the most common genotype among β-thalassemia, Meanwhile, two α-mutation sites are found in this study which were not reported in the Database of Human Hemoglobin Variants and Thalassemias.
China ; Female ; Genotype ; Humans ; Mutation ; Pregnancy ; alpha-Thalassemia ; beta-Thalassemia

Papillary thyroid carcinoma (PTC) can exhibit lateral neck lymph node metastasis at an early stage. Lateral neck lymph node metastasis is a crucial factor affecting the prognosis of PTC and is an absolute indication for neck lymph node dissection surgery. Additionally, it is a relative contraindication of endoscopic surgery for most medical centers. Therefore, the preoperative identification of lateral neck lymph node metastasis is vital for surgical decision-making and prognosis assessment. Ultrasound, CT, cytology, and clinical features can provide some information on lateral neck lymph node metastasis, but their accuracy does not fully meet clinical needs. Deep learning is a primary method for medical image recognition or feature extraction. In recent years, deep learning-based ultrasound, CT, cytology, conventional clinical parameters, or multimodal models combining these data have been developed and are expected to achieve routine clinical application. With the establishment and sharing of large datasets, automated annotation, algorithm optimization, and resolution of data security issues, deep learning is expected to accurately predict lateral neck lymph node metastasis in PTC. Furthermore, it can be integrated into electronic medical record systems for automated real-time analysis and assist clinical decision-making.

OBJECTIVE: To evaluate the clinical efficacy and safety of Congrong Shujing Granules ( , CSGs) in treating patients with Parkinson's disease (PD) and Chinese medicine (CM) syndrome of Shen (Kidney) essence deficiency, and to investigate the potential mechanism involving efficacy through a transcriptome sequencing approach. METHODS: Eligible PD patients with syndrome of Shen essence defificiency were randomly assigned to a treatment group or a control group by a random number table, and were treated with CSGs combined with Western medicine (WM), or placebo combined with WM, respectively. Both courses of treatment lasted for 12 weeks. The Unifified Parkinson's Disease Rating Scale (UPDRS) score, the PD Question-39 (PDQ-39) score, CM Syndrome Scale score, and drug usage of all patients were evaluated before and after treatment. Safety was evaluated by clinical laboratory tests and electrocardiographs. Blood samples from 6 patients in each group were collected before and after the trial and used for transcriptomic analysis by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Differentially expressed genes were validated using reverse transcription-polymerase chain reaction. RESULTS: A total of 86 PD patients were selected from the Third Affifiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2017 and December 2017. Finally, 72 patients completed the trial, including 35 in the treatment group and 37 in the control group. When compared with the control group after treatment, patients in the treatment group showed signifificant decreases in UPDRS sub-II score, PDQ-39 score, CM syndrome score, and Levodopa equivalent dose (P<0.05). During the treatment course, no signifificant changes were observed in safety indicators between the two groups (P>0.05). A possible mechanism of clinical effificacy was proposed that involved regulating cell metabolism-related processes and ribosome-related pathways. Treatment with CSGs had shown to affect relevant gene loci for PD, including AIDA, ANKRD36BP2, BCL2A1, BCL2L11, FTH1P2, GCH1, HPRT1, NFE2L2, RMRP, RPS7, TGFBR1, WIPF2, and COX7B. CONCLUSIONS CSGs combined with WM can be used to treat PD patients with CM syndrome of Shen essence defificiency with a good safety. The possible mechanism of action and relevant gene loci were proposed. (Registration No. ChiCTR-IOR-16008394).