[Efficacy and influencing factors of immunotherapy combined with chemotherapy and bevacizumab in patients with non-small cell lung cancer after epidermal growth factor receptor tyrosine kinase inhibitors treatment failure].

Objective: To investigate the efficacy and influencing factors of immunotherapy combined with chemotherapy and bevacizumab in patients with non-small cell lung cancer (NSCLC) who failed epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. Methods: A retrospective analysis was made on the clinical data of 60 NSCLC patients who were treated with immunotherapy combined with chemotherapy and bevacizumab after EGFR-TKIs treatment failure in the Affiliated Cancer Hospital of Shandong First Medical University from January 2019 to March 2022. Patients were followed up by telephone or outpatient review up to October 1, 2022, with a median follow-up of 8.2 months (95%CI: 7.1-9.3). All 60 patients were followed up. The response evaluation criteria in solid tumors were used to evaluate the short-term efficacy. The adverse reactions of patients were evaluated according to the common terminology criteria for adverse events. The survival curve was drawn by Kaplan-Meier method. Cox proportional hazard regression models were utilized to analyze the influencing factors of progression-free survival (PFS). Results: Among the 60 NSCLC patients, 22 were males. The age ranged from 41 to 75 years, with a median age of 61 years. Eleven patients had partial response, 19 patients had stable disease and 30 patients had progressive disease. The median PFS was 8.2 months (95%CI: 7.2-9.2). The median PFS of patients with low expression of programmed death receptor-ligand 1 (PD-L1) [Tumor cell Proportion Score (TPS)<1%], moderate expression of PD-L1 (1%≤TPS≤49%), and high expression of PD-L1 (TPS≥50%) were 6.4 (95%CI: 4.8-8.0), 8.3 (95%CI: 7.3-9.3) and 10.6 months (95%CI: 7.2-14.1), respectively, and there were statistically significant differences (χ2=13.58, P<0.001). Multivariate Cox proportional risk regression model analysis showed that age>65 years old (HR=4.017, 95%CI: 1.468-10.992, P=0.007) was a risk factor for PFS in NSCLC patients who received immunotherapy combined with chemotherapy and bevacizumab after EGFR-TKIs treatment failure. Moderate expression of PD-L1 (HR=0.360, 95%CI: 0.139-0.930, P=0.035) and high expression of PD-L1 (HR=0.155, 95%CI: 0.039-0.625, P=0.009) were protective factors for PFS. Most of the treatment-related adverse reactions in the whole group were grade 1-2, including bone marrow suppression (n=24), nausea (n=25), decreased appetite (n=24), fatigue (n=22), vomiting (n=18), abnormal liver function (n=17), blood creatinine increased (n=10), and so on. These were tolerated by the patients. Conclusions: NSCLC patients who failed EGFR-TKIs treatment can tolerate adverse reactions related to immunotherapy combined with chemotherapy and bevacizumab treatment. PFS is significantly prolonged in those aged≤65 years and those with moderate and high expression of PD-L1.

[Value of high-resolution anoscopy in the diagnosis of anal precancerous lesions].

Objective: To evaluate the value of high-resolution anoscopy (HRA) in the diagnosis of anal precancerous lesions. Methods: A retrospective cohort study was performed, which included 142 patients who underwent HRA in vulvar and anal clinic at Obstetrics and Gynecology Hospital of Fudan University from January 2014 to December 2019. With the perianal and anal canal biopsy pathology as the "gold standard", the diagnostic value of HRA and specific findings for anal precancerous lesions were evaluated and the clinical characteristics of patients with anal precancerous lesions were analyzed. Results: (1) Agreement between HRA and anal pathology were 76.6% (95/124, perianal) and 70.0% (84/120, anal canal), in which there was no significant difference (χ2=1.365, P=0.243). The strength of agreement with weighted Kappa statistic were 0.604 (perianal) and 0.455 (anal canal) respectively. HRA diagnosis were more overestimated [16.9% (21/124) in perianal and 25.0% (30/120) in anal canal] than underestimated [6.5% (8/124) in perianal and 5.0% (6/120) in anal canal]. The sensitivity and specificity of HRA in the diagnosis of anal precancerous lesions were all more than 60.0% (perianal lesions: 97.8% and 74.7%; anal canal lesions: 90.9% and 66.7%), and Youden's index were >0.5 (perianal lesions: 0.725; anal canal lesions: 0.576). The positive predictive value of HRA in anal canal lesions (50.8%) was lower than that in perianal lesions (68.8%). (2) The thin acetowhite epithelium was the most common finding in anal precancerous lesions, and its performance in anal canal lesions (the sensitivity, the specificity and the Youden's index were 78.8%, 62.4% and 0.412, respectively) were better than those in perianal lesions (the sensitivity, the specificity and the Youden's index were 28.9%, 96.9% and 0.258, respectively). The dense acetowhite epithelium and vascular patterns were only seen in anal canal lesions. Lugol's iodine was little useful for perianal lesions (the incidence of iodine negative was 0),but quite useful to evaluate the canal lesions (the positive predictive value was 83.3% and the negative predictive value was 82.3%). (3) The average age of patients with low-grade anal precancerous lesion was (37±10) years old, and high-grade anal precancerous lesion was (42±11) years old, and there was significant difference between them (P=0.034). Age curve showed that the peak age was 30-40 years old. Vulvar intraepithelial lesion was the risk factor of anal precancerous lesions (χ2=4.284, P<0.05). Conclusions: HRA patterns are reliable in the diagnosis of anal precancerous lesions, which is important for guiding biopsy. However, it is easy to be overestimated, especially for anal canal lesions. The acetowhite epithelium is the most common finding in anal precancerous lesions, but vascular patterns are only seen in anal canal lesions.

[Analysis of lens opacity and its influencing factors of medical radiation workers].

Objective: To explore the association between long-term low-dose radiation exposure and other influencing factors with the risk of lens opacity on medical radiation workers. Methods: In July 2019, a retrospective cohort study was conducted by collecting the basic demographic information, dose data and health inspection result of 2708 radiologists in 22 hospitals of Guangzhou from the Occupational Health Inspection Information System and the Personal Dose Monitoring System of the Guangdong Prevention and Treatment Center for Occupational Disease between 2010 to 2018. The association between the average annual effective dose and lens opacity risk was calculated by using Time-Dependent Cox Regression Model. Results: From 2010 to 2018, the incidence density of lens opacity was 185.90/10000 person years. Compared with the radiation workers in the age <30 years group (93.74%) , the 5-year normal rate of lens in the age ≥50 years group (72.51%) was lower (P<0.01) ; Compared with the radiation workers in the exposure age <10 years group (92.69%) , the 5-year normal rate of lens in more than 20 years exposed group (83.05%) was lower (P<0.01) . Multifactor analysis showed that age was an independent influencing factor for lens opacity in medical radiation workers (HR=14.485, P<0.01) . The risk of lens opacification increased by 4.9%, 10.1% and 15.5% in 30-, 40- and 50-years group, respectively. Gender, cigarette, alchol, type of work, length of service and annual effective dose had no significant effect on lens opacity (P>0.05) . Conclusion: Age is the main influencing factor of lens opacification in medical radiation workers, their radiation working time and intensity should be strictly controlled and radiation protection should be done.

[Regulatory effect of miR-30b on migration and invasion of pancreatic cancer stem cells].

Objective: To detect the expression of micro RNA(miRNA, miR)-30bin pancreatic cancer stem cells (PCSCs) and to observe the regulatory effect of miR-30b on epithelial-mesenchymal transformation (EMT) process, migration and invasion of PCSCs. Methods: CD24, CD44 and EpCAM triple-positive PCSCs in pancreatic ductal adenocarcinoma(PDAC) cell line PANC-1 were sorted out by flow cytometry and the expression of Nanog and Oct4 were evaluated. The expression profile of miR-30 family in PCSCs and common cancer cells was analyzed, and the memberwith the most obvious differential expression was selected.miR-30b mimic was transfected into PCSCs and then RT-qPCR or Western Blot were performed to investigate the expression of EMT markers. The effect of miR-30b on the migration and invasion ability of PCSCs was detected by Transwell assay. Then, miR-30b agomir was transfected into PCSCs and inoculated in nude mice to study the effect of mir-30b on the tumorigenic ability. Results: PCSCs accounted for 4.52-8.09% of the total. The mRNA and protein levels of Oct4 and Nanog of PCSCswere significantly higher than those of PANC-1(P<0.001). The expression levels of miR-30b, c and d were significantly down-regulated, among which miR-30b was the most significant. After miR-30b overexpression in PCSCs, E-cadherin was significantly up-regulated (P<0.001), N-cadherin (P<0.001) and transcription factor Snail (P<0.001) were significantly down-regulated, while vimentin expression was not significantly changed. Transwell assay showed that both migration and invasiveness of PCSCs were significantly decreased after transfection (P<0.001). In vivo experiments, the tumor volume and weight of the nude mice injected with PCSCs overexpressing miR-30b were also significantly lower than those of the control group (P<0.01). Conclusions: CD24, CD44 and EpCAMtriple positive PCSCs in pancreatic cancer cells showed obvious stemness characteristics. miR-30b can reverse the EMT process of PCSCs, reduce their migration and invasion, and inhibit the tumorigenicity of PCSCs.

[Clinical analysis of transumbilical single-incision laparoscopic cholecystectomy with totally free umbilical ring by conventional instruments].

Objective: To summarize the clinical experience of transumbilical single-port laparoscopic cholecystectomy, and evaluate its clinical utility and the feasibility of widely usage. Methods: Between April 2012 and June 2017, 500 cases who underwent transumbilical single-port laparoscopic cholecystectomy with totally free umbilical ring by conventional instruments were enrolled. The clinical data were retrospectively analyzed. Results: A total of 487 patients were successfully completed the operation. In addition, 3 cases were converted to open cholecystectomy, 10 cases were converted to multi-port laparoscopy and drainage tubes were placed in 5 cases. The mean operating time of transumbilical single-port laparoscopic cholecystectomy(from the Trocars being put to the gallbladders being removed)shortened from 72.3 min to 13.2 min. The average bleeding amount was less than 10 ml. After the operation, 3 cases had delayed bile leakage and 3 cases had transient up-regulation of bilirubin at the beginning of the technique. No patients had hemorrhage and Trocar hernia. The average hospital stay of patients was 2.1 days. The cosmetic effect was remarkable during follow-up. Conclusion: The transumbilical single-port laparoscopic cholecystectomy with totally free umbilical ring by conventional instruments should be widely carried out in hospitals at all levels because of its minimal postoperative pain, rapid recovery, hidden incision, low costs and low incidence of port-site hernia.

[Detection trend of vaginal intraepithelial neoplasia diagnosed by colposcopy guided biopsy from 2013 to 2015].

Objective: To explore the detection trend of vaginal intraepithelial neoplasia (VaIN) of lower genital tract from 2013 to 2015. Methods: A retrospective analysis was undertaken of colposcopy-directed biopsy of cervical, vaginal and vulvar intraepithelial neoplasia lesions include cervical intraepithelial neoplasia (CIN), VaIN and vulvar intraepithelial neoplasia (VIN) in Obstetrics and Gynecology Hospital of Fudan University from January 2013 to December 2015. Results: (1) Overall data of CIN, VaIN and VIN: a total of 16 732 cases were diagnosed of lower genital intraepithelial neoplasia in 3 years, accounting for 23.20% (16 732/72 128) of total colposcopy-directed biopsy cases. Among them, CIN, VaIN and VIN accounted for 19.48% (14 053/72 128), 2.67% (1 923/72 128), 1.05% (756/72 128) of total colposcopy-directed biopsy cases of the lower genital tract, 83.99% (14 053/16 732), 11.49% (1 923/16 732), 4.52% (756/16 732) of total lower genital intraepithelial neoplasia, respectively. (2) Annual data of CIN, VaIN and VIN from 2013 to 2015. The annual proportion of CIN in all intraepithelial neoplasia of lower gential tract was basically stable, consisting of 86.02%(3 955/4 598),83.25%(4 795/5 760) and 83.20% (5 303/6 374), respectively. The annual proportion of VaIN was gradually increasing, consisting of 8.09%(372/4 598), 12.45%(717/5 760) and 13.08%(834/6 374), respectively. The annual proportion of VIN was gradually decreasing, consisting of 5.89%(271/4 598), 4.31%(248/5 760) and 3.72%(237/6 374), respectively. Conclusion: The increasing detection of VaIN from 2013 to 2015 might correlate with the increasing attention to inspection of the entire vaginal wall.

[Clinical analysis of laparoscopic surgery in patients with maintenance hemodialysis and colon cancer].

OBJECTIVE: To explore the safety of laparoscopic assisted radical resection of colon cancer in uremic patients. METHODS: Retrospective analysis of Zhejiang Jinhua Guangfu hospital 2012 March to 2015 March 5 cases of uremia patients complicated with colon cancer underwent laparoscopic assisted colorectal cancer radical resection, and compared with 10 cases, observing two groups of operative time, intraoperative bleeding volume, postoperative drainage volume, lymph nodes dissect, anal exhaust time, postoperative complications, postoperative hospitalization time and postoperative pathological staging. RESULTS: Before operation two groups of age, gender, tumor location was no significant difference (P>0.05). In preoperative comorbidities uremic patients were significantly more than that of ordinary patients, mainly in cardiovascular complications, and patients in the two groups in operation time, intraoperative bleeding, post operative drainage volume, lymph node dissection numbers were no significant difference, the postoperative gastrointestinal function recovery was almost no difference, but postoperative hospitalization time significantly prolonged (P<0.05). CONCLUSIONS: Patients with uremia as long as full preoperative preparation, perioperative management, plus timely hemodialysis, uremia patients undergoing laparoscopic assisted radical surgery is safe and feasible, and it is worth promoting.

Unbalanced translocation in an adult patient with premature ovarian failure and mental retardation detected by spectral karyotyping and array-comparative genomic hybridization.

BACKGROUND: There are only three cases of unbalanced translocation (X;1) reported in childhood in the literature, while no such phenotypic information is available in adults. MATERIALS AND METHODS: To delineate the phenotype-genotype relationship of unbalanced translocation (X;1) in adulthood, we reported here a 20-year-old female with an unbalanced translocation (X;1) which was determined by spectral karyotyping, array-comparative genomic hybridization and subtelomeric fluorescence in situ hybridization (FISH). RESULTS: The phenotype of partial trisomy 1 and partial monosomy X of the present case was much attenuated, including premature ovarian failure, mental retardation, class I obesity, mild dysmorphism and delayed secondary sexual characteristics. The breakpoints of the unbalanced translocation were accurately located at Xq28 and 1q32.1. The large amplification on Chromosome 1 q arm was found to involve 312 genes and the deletion on Chromosome X q arm also involved 141 genes. Overall, genes associated with physiological process (47 genes), cellular process (33), development (23), response to stimulus (1) and reproduction (1) were observed in the amplification on Chromosome 1 q arm. In addition, genes related to physiological process (23 genes), cellular process (13), development (6) and response to stimulus (2) were observed in the large deletion on chromosome X q arm. Late-replication studies revealed the existence of skewed X inactivation in the derivative X chromosome. CONCLUSIONS: The phenotype of partial monosomy X and partial trisomy 1q is much attenuated in case of unbalanced translocation (X;1) in adulthood probably owing to skewed X inactivation in derivative X chromosome.

Polymorphisms of CD14 gene and TLR4 gene are not associated with ulcerative colitis in Chinese patients.

BACKGROUND AND AIMS: Toll-like receptor 4 and CD14 are the components of the lipopolysaccharide receptor complex. The aim of this study was to investigate the associations between polymorphisms TLR4 Asp299Gly and CD14 C-260T and Chinese patients with ulcerative colitis (UC). METHODS: Using a polymerase chain reaction based restriction fragment length polymorphism, the study genotyped polymorphisms TLR4 Asp299Gly and CD14 C-260T in 114 patients with UC and 160 healthy controls in the Chinese Han population. Moreover a comparison was made with 170 healthy Dutch white subjects. RESULTS: No TLR4 Asp299Gly mutation was detected in any patients or healthy controls in the Chinese Han population, which was similar to Japanese subjects, but the mutation occurred in 10% of the Dutch white subjects. There were no significant differences of CD14 genotypes between healthy controls and the patients with UC.

Germ cell apoptosis induced by ureaplasma urealyticum infection.

AIM: To study the effect of Ureaplasma urealyticum (UU) infection on germ cell apoptosis of male rats. METHODS: Male rats were infected artificially with UU serotype 8 (T960). Morphological changes of germ cells in the seminiferous tubules and the lumen of the epididymides were observed under the light microscope. Fluorescence-conjugated polyclonal antibodies to Fas and Fas ligand (FasL) were used to localize Fas and FasL. TUNEL staining of germ cells and Sertoli cells was performed by the AKPase method. TUNEL-positive rate (% positive cells) and TUNEL-positive area (area occupied by stained cells) were analysed by KS400 Image Analysis System. The DNA laddering analysis was performed by agarose gels electrophoresis. RESULTS: In those rats infected with UU: (1) Exfoliated germ cells were dramatically increased. Many multinucleated giant cells were found in the seminiferous tubules and the lumen of the epididymides. (2) The number of TUNEL-positive cells and the TUNEL-positive area were significantly increased. (3) The expression of Fas and FasL in germ cells and Sertoli cells was up-regulated. (4) Discrete bands of fragmented DNA were found in the testicular cells. CONCLUSION: In male rats, germ cell apoptosis was increased in UU infection.

[Study on growth rhythm in populations of Pinellia ternata (Thunb.) Breit].

OBJECTIVE: To study the genetic diversity of Pinellia ternata. the growth rhythm. METHOD: Sixteen populations of P. ternata. originated mostly from middle and lower reaches of Yangtze River valley were collected and cultivated in Weigang Experimental Farm of Nanjing Agricultural University with same cultural conditions, whose differences in growth rhythm have been observed and compared continuously for two years. RESULT AND CONCLUSION: There are obvious differences in sprouting, lamina spreading, bolting and "sprout tumble", Three times of "sprouting" and so-called "sprout tumble" and two fast-growing periods for plants in most of the populations in spring and autumn respectively were observed within a year, including mass bolting in May. But the starting time and duration are very different from population to population, with flowering being prior to sprouting in the population originated from Jurong county.

[Comparative study on three types of chemicals extracted from tubers of populations of Pinellia ternata (Thunb.) Breit].

OBJECTIVE: To study the genetic diversity of Pinellia ternata. on the chemical composition. METHOD: Fifteen populations of Pinellia ternata. originated mostly from middle and lower reaches of Yangtze River valley were collected and cultivated in Weigang Experimental Farm of Nanjing Agricultural University with same cultural conditions, and contents in three types of index chemicals extracted from tubers of the populations have been compared continuously. RESULT AND CONCLUSION: The difference in contents of beta-sitosterol and Val and Arg extracted from tubers of the populations has been observed, and those contents are also different with harvesting time. But the mean contents of each of the three types of chemicals in autumn are all higher than those in summer respectively.

[Advances in research on Chinese medicinal plant breeding].

In this paper, the author reviewed the study in Chinese medicinal plant breeding from the following aspects: selection breeding, crossbreeding, induced mutation breeding, tissue culture and improved variety propagation, etc.