Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To investigate the relationship between serum L-carnitine and its related metabolites[trimethylamine(TMA)and trimethylamine N-oxide(TMAO)]levels and gestational diabetes mellitus(GDM)in the second trimester of pregnant women in Shanghai.Methods A case-control study was conducted in 280 pregnant women between 18 and 23 weeks of gestation from January 2018 to January 2021.Among them,134 cases of GDM were the case group(GDM),and 146 cases with normal blood glucose(BG)were the control group(Con).Serum L-carnitine,TMA and TMAO levels were quantified by ultra high performance liquid chromatography-mass spectrometry.Logistic regression analysis,stratified analysis and linear regression were used to explore the relationship between L-carnitine,TMA and TMAO levels and GDM and glucolipid metabolism.Results Serum L-carnitinelevelwas significantly lower in GDM group than that in Con group(P<0.01).After adjusting for confounders,logistic regression showed a 70%reduction in the risk of GDM in the group with highest tertile of L-carnitine compared with the group with lowest tertile(OR 0.30,95%CI 0.15～0.63).The risk of GDM decreased by 14%for each 1 μmol/L increase in serum L-carnitine(OR 0.86,95%CI 0.80～0.93).Serum L-carnitine was negatively correlated with 1 hPG(r=-0.21,P<0.01)and 2 hPG(r=-0.15,P<0.05),respectively,TMA was negatively correlated with 2 hPG(r=-0.21,P<0.01).Conclusions Higher serum L-carnitine level may be negatively associated with GDM.Serum L-carnitine and TMA levels were negatively correlated with blood glucose levels.

[Abstract] Objective: To investigate the effect of HMGB1 gene on the growth of human epithelial ovarian cancer xenografts in nude mice, and to lay a foundation for finding new targets for the treatment of ovarian cancer. Methods: Human epithelial ovarian cancer SKOV3 cells in logarithmic growth phase were selected to establish a human epithelial ovarian cancer xenograft model in nude mice. Nude mice with successful model establishment were randomly divided into control group and HMGB1-siRNA group. On the 7th, 9th, 11th, 14th, and 16th days after cell inoculation, the same amount of saline and HMGB1-siRNA were respectively injected into two groups of mice under the armpit.After 3 weeks, the nude mice were sacrificed by cervical dislocation, the tumor tissues were separated, and the volume of the tumor was measured. The apoptosis of transplanted tumor cells was detected by Tunnel staining. The expressions of HMGB1, STAT3 and p-STAT3 were detected by Western blotting. The expression of vascular endothelial growth factorA(VEGF-A) and microvascularization were detected by immunohistochemistry. Results: Compared with the control group, the growth of tumor volume slowed down in HMGB1 siRNA group, and on the 21st day, the tumor volume of HMGB1-siRNA group was significantly smaller than that of the control group (P<0.05). HMGB1-siRNA successfully knocked down the expression of HMGB1 mRNA in transplanted tumor tissue. The apoptosis rate of tissue cells in HMGB1-siRNA group was significantly increased ([34±8]% vs [6±2]%, P=0.04), and the expressions of HMGB1 and p-STAT3 were significantly reduced (P<0.05). The expression of VEGF-Aand the number of microvessels were significantly lower than those of the control group (both P<0.05). Conclusion: Knockdown of HMGB1 gene reduces the expression of VEGF-A and microvessel formation possibly by inhibiting the HMGB1/STAT3 signaling pathway, thereby promoting the apoptosis of tumor tissues and slowing the growth of xenografts.

Objective To observe the changes of peripheral blood lymphocyte subsets in patients with postoperative colorectal cancer before and after chemotherapy, and to evaluate the changes of immune function status. Methods 74 patients with stage Ⅱ-Ⅲ colorectal cancer after radical resection admitted in Zhejiang Cancer Hospital from January to December 2016 were enrolled. 25 non-malignant patients in the same period in our hospital were selected as the control group. Flow cytometry was used to analyze the proportion of peripheral blood lymphocyte subsets at one day before the first, sixth and eighth cycles of adjuvant chemotherapy. Results There were no differences in CD3+ (P =0.1532), CD3+CD4+ (P=0.1107), CD3+CD8+ (P=0.2576) T cells in the peripheral blood between patients with colorectal cancer after radical operation and control group (P>0.05). While CD3+CD56+NKT cells (P=0.0210) and CD3-CD56+NK cells (P=0.0045) in the patients with colorectal cancer after radical operation were significantly higher than those of the control group (P <0.05). There was no significant change in the proportion of NK and NKT cells before 6 cycles of postoperative adjuvant chemotherapy (P>0.05). There was no significant change in the proportion of NKT cells before 8 cycles (P>0.05), and the proportion of NK cells only decreased slightly (19.10±4.63 vs 20.31±4.66, P=0.046). Conclusion The proportion of NK and NKT cells in patients with colorectal cancer after radical resection was significantly higher than that in healthy people, and the expression rate remains stable after adjuvant chemotherapy.

Objective To explore the effect of sitting and lateral sputum aspiration on the retention time of tracheal cannula in patients with neurosurgical tracheotomy. Methods Totally 120 cases of neurosurgery tracheotomy in hospitalized patients complicated with pulmonary infection by random number table method, 58 cases were divided into experimental group and control group 62 examples, two groups of patients with sputum top all joint taps to the back of the chest, the experimental group after taps take seat effectively causes cough; In the control group, the lateral position was used to effectively cough or induce cough, and the daily sputum volume of the two groups of patients was observed. To observe the time when the body temperature was restored to normal after the phlegm of the two groups of patients, the time of the lung auscultation, and the time of the tracheal tube retention. Results Implementing position row of phlegm daily sputum volume within a week the experimental group were (44.84±6.85) ml, (44.60±6.80) ml, (43.79±5.98) ml, (44.38±5.42) ml, (42.22±5.45) ml, (38.12±4.77) ml, (36.88±4.57) ml and control group were(36.13±7.34) ml, (35.15±7.34) ml, (36.13±7.34) ml, (37.13±7.34) ml, (37.13±7.34) ml, (32.97±7.17) ml, (31.35±4.36) ml, the difference had statistical significance (t=4.30-7.31, P<0.01);In the two groups, the time of normal body temperature recovery, the time of hearing and the time of the lung and the time spent in the tracheal tube were compared, and the experimental group were respectively (9.93±2.02) d, (32.33±1.50) d, (37.33±1.50) d, while control group were(15.77±1.05) d, (37.63 ± 2.33) d, (42.63 ± 2.33) d, the difference had statistical significance (t=20.04, 14.71, P<0.01). Conclusions It is better to reduce the retention time of tracheal tube in patients with neurosurgical patients than the lateral position.

Objective · To obtain the latest data on phospholipid composition of human milk in Shanghai and compare the differences in phospholipid composition at different lactation stages. Methods · Healthy postpartum women who delivered full-term infants in the Obstetrical Department of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between April and July, 2016 were enrolled. The colostrum, transitional milk, and mature milk were collected at Day 3, 10, and 45 after delivering babies, respectively. Human milk fat was extracted with Folch's method and phospholipids were separated with solid phase extraction (SPE). The phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin were quantitatively analyzed with HPLC/VWD. The differences in phospholipid composition at different lactation stages were compared with univariate analysis of variance and Games-Homell test. Results · One hundred women who provided at least one breast milk sample were enrolled. A total of 70 colostrum samples, 96 transitional milk samples, and 82 mature milk samples were collected. The total phospholipid content of mature milk [(281.93±118.54) μg/g] was significantly lower than that of colostrum [(381.99±205.90) μg/g]. At all lactation stages, the relative content of phosphatidylcholine was the highest (53.74%-59.36%), followed by sphingomyelin (28.12%-32.74%). The relative content of phosphatidylethanolamine was constant (P=0.617), the relative content of phosphatidylcholine gradually decreased (P=0.000), and that of sphingomyelin gradually increased (P=0.000) during the lactation. Conclusion · Sphingomyelin and phosphatidylcholine are major components of human milk phospholipids. The amount of phospholipids varies during the lactation. The total amount of phospholipids is lower in mature milk than in colostrum and transitional milk. The relative content of phosphatidylethanolamine is consistent at all lactation stages, the relative content of phosphatidylcholine gradually decreases, and that of sphingomyelin gradually increases.

Objective To investigate the relationship on the excision repair cross complementing gene 1(ERCC1)‐4533/8092 site single nucleotide polymorphisms(SNPs) and the susceptibility to hepatocellular carcinoma(HCC) in Guangxi Zhuang population . Methods Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method was used to detect the ER‐CC1‐4533/8092 gene polymorphism in 88 cases with primary liver cancer and 82 cases of normal controls .Results There was no difference in the frequency distribution of ERCC1‐4533 in the case group and the control group ,the frequency distribution of the ERCC1‐8092 in the case group and the control group was different(P< 0 .05) .Compared with ERCC1‐8092 CC ,ERCC1‐C8092 CA/AA had higher risk of primary hepatocellular carcinoma(CA :OR=2 .556 ,95% CI:1 .345 -4 .855;AA :OR= 8 .667 ,95% CI:1 .000-75 .092) .ERCC1‐8092 C allele as a reference ,ERCC1‐8092 A allele can increase the risk of primary liver cancer (OR=2 .387 ,95% CI:1 .428-3 .992) .Conclusion The genetic polymorphisms of ERCC1‐8092 sites are associated with susceptibility to hepatocellular carcinoma in Guangxi Zhuang population .

Red-based recombineering has been widely used in Escherichia coli genome modification through electroporating PCR fragments into electrocompetent cells to replace target sequences. Some mutations in the PCR fragments may be brought into the homologous regions near the target. To solve this problem in markeless gene deletion we developed a novel method characterized with two-step recombination and a donor plasmid. First, generated by PCR a linear DNA cassette which comprises a I-Sec I site-containing marker gene and homologous arms was electroporated into cells for marker-substitution deletion of the target sequence. Second, after a donor plasmid carrying the I-Sec I site-containing fusion homologous arm was chemically transformed into the marker-containing cells, the fusion arms and the marker was simultaneously cleaved by I-Sec I endonuclease and the marker-free deletion was stimulated by double-strand break-mediated intermolecular recombination. Eleven nonessential regions in E. coli DH1 genome were sequentially deleted by our method, resulting in a 10.59% reduced genome size. These precise deletions were also verified by PCR sequencing and genome resequencing. Though no change in the growth rate on the minimal medium, we found the genome-reduced strains have some alteration in the acid resistance and for the synthesis of lycopene.
Chromosomes, Bacterial ; genetics ; DNA ; Endonucleases ; metabolism ; Escherichia coli ; genetics ; Genetic Engineering ; methods ; Recombination, Genetic ; Sequence Deletion

OBJECTIVETo investigate the efficacy and adverse effect of DCF regimen with subsequent S-1 maintenance chemotherapy in patients with advanced gastric cancer (AGC).

METHODSSixty AGC patients without disease progression after 4 to 6 cycles of DCF regimen as the first-line chemotherapy were randomized into maintenance group and control group (30 patients each). The patients in the maintenance group received maintenance chemotherapy with S-1 (40 mg/m(2), twice daily for 14 days; 21 days for a treatment cycle) until disease progression or with intolerant toxicity, and those in the control group received optimal supportive care.

RESULTSThe response rate (CR+PR) was 33.3% in the maintenance group, significantly higher than that in the control group (3.33%, P<0.05), and the disease control rate (CR+PR+SD) also differed significantly between the two groups (73.3% vs 46.7%, P<0.05). The median time to progression was 7.9 months in the maintenance group and 6.8 months in the control group, with median overall survival time of 13.8 and 11.7 months, respectively (P>0.05). The most common adverse effect in the maintenance group included nausea, vomiting, leucocytopenia, and hand-foot syndrome; no death occurred in relation to the therapy.

CONCLUSIONS-1 maintenance chemotherapy, with a tolerable toxicity profile, can improve the RR, DCR and median time to progression in AGC patients who respond to DCF regimen, but its efficacy still awaits further evaluation.

Objective To investigate the efficacy and adverse effect of DCF regimen with subsequent S-1 maintenance chemotherapy in patients with advanced gastric cancer (AGC). Methods Sixty AGC patients without disease progression after 4 to 6 cycles of DCF regimen as the first-line chemotherapy were randomized into maintenance group and control group (30 patients each). The patients in the maintenance group received maintenance chemotherapy with S-1 (40 mg/m2, twice daily for 14 days; 21 days for a treatment cycle) until disease progression or with intolerant toxicity, and those in the control group received optimal supportive care. Results The response rate (CR+PR) was 33.3%in the maintenance group, significantly higher than that in the control group (3.33%, P<0.05), and the disease control rate (CR+PR+SD) also differed significantly between the two groups (73.3% vs 46.7%, P<0.05). The median time to progression was 7.9 months in the maintenance group and 6.8 months in the control group, with median overall survival time of 13.8 and 11.7 months, respectively (P>0.05). The most common adverse effect in the maintenance group included nausea, vomiting, leucocytopenia, and hand-foot syndrome; no death occurred in relation to the therapy. Conclusions S-1 maintenance chemotherapy, with a tolerable toxicity profile, can improve the RR, DCR and median time to progression in AGC patients who respond to DCF regimen, but its efficacy still awaits further evaluation.