Objective To elucidate the kinetic characteristics of viral replication and transcription,an in vitro model of viral replication and transcription was established.Utilizing single-molecule magnetic tweezers technology,the dynamic process of SARS-CoV-2 RNA-dependent RNA polymerase(RdRp)during in vitro replication and transcription was investigated.Methods The force field of the single-molecule magnetic tweezer system was corrected using DNA fragments,followed by the construction of RNA fragments to explore the kinetics of RdRp replication and transcription in vitro.Results The force field calibration results were consistent with the worm-like chain model(WLC).The ssRNA strand was found to be approximately 0.3 pm longer than the dsRNA strand and could be stably extended under a 30 pN force field.The average synthesis rate of RdRp extension was determined to be 3.27 nt/s,with an average processivity of 886 nt.Conclusions By implementing force calibration in single-molecule magnetic tweezers,the real-time tracking of RdRp kinetics during the full-cycle replication-transcription process(initiation,elongation,and termination)in vitro was achieved,thereby constructing a mechanistic model of RdRp-driven nucleic acid synthesis.This study provides a basis for further investigating the kinetics of viral RdRp in physiological processes including replication,transcription,and backtracking under varied in vitro environments using single-molecule magnetic tweezers,and establishes a single-molecule manipulation framework for evaluating the effects of therapeutic compounds on viral replication-transcription processes in vitro.

Objective:To retrieve, evaluate, and summarize evidence on the nonpharmacological management of chemotherapy-induced peripheral neuropathy (CIPN) to provide an evidence-based basis for the clinical nursing of patients undergoing cancer chemotherapy.Methods:In accordance with the "6S" model of evidence-based search resources, guidelines, evidence summaries, clinical decisions, expert consensus, and systematic reviews on the nonpharmacological management of CIPN were systematically searched on domestic and international websites or databases. The search period was from January 1, 2019 to December 31, 2023.Results:A total of 19 papers were included, including one evidence summary, one guideline, six expert consensus, and 11 systematic reviews. Forty pieces of best evidence in five aspects of assessment/screening, prevention, intervention, clinical management, and health education were summarized.Conclusions:The 40 best evidence for nonpharmacological management of CIPN summarized can be used to prevent or reduce CIPN in cancer patients. Clinical medical and nursing staff should select evidence entries as appropriate for different clinical situations, taking into account the patient's own condition and the feasibility and appropriateness of evidence implementation.

Objective To elucidate the kinetic characteristics of viral replication and transcription,an in vitro model of viral replication and transcription was established.Utilizing single-molecule magnetic tweezers technology,the dynamic process of SARS-CoV-2 RNA-dependent RNA polymerase(RdRp)during in vitro replication and transcription was investigated.Methods The force field of the single-molecule magnetic tweezer system was corrected using DNA fragments,followed by the construction of RNA fragments to explore the kinetics of RdRp replication and transcription in vitro.Results The force field calibration results were consistent with the worm-like chain model(WLC).The ssRNA strand was found to be approximately 0.3 pm longer than the dsRNA strand and could be stably extended under a 30 pN force field.The average synthesis rate of RdRp extension was determined to be 3.27 nt/s,with an average processivity of 886 nt.Conclusions By implementing force calibration in single-molecule magnetic tweezers,the real-time tracking of RdRp kinetics during the full-cycle replication-transcription process(initiation,elongation,and termination)in vitro was achieved,thereby constructing a mechanistic model of RdRp-driven nucleic acid synthesis.This study provides a basis for further investigating the kinetics of viral RdRp in physiological processes including replication,transcription,and backtracking under varied in vitro environments using single-molecule magnetic tweezers,and establishes a single-molecule manipulation framework for evaluating the effects of therapeutic compounds on viral replication-transcription processes in vitro.

Objective:To retrieve, evaluate, and summarize evidence on the nonpharmacological management of chemotherapy-induced peripheral neuropathy (CIPN) to provide an evidence-based basis for the clinical nursing of patients undergoing cancer chemotherapy.Methods:In accordance with the "6S" model of evidence-based search resources, guidelines, evidence summaries, clinical decisions, expert consensus, and systematic reviews on the nonpharmacological management of CIPN were systematically searched on domestic and international websites or databases. The search period was from January 1, 2019 to December 31, 2023.Results:A total of 19 papers were included, including one evidence summary, one guideline, six expert consensus, and 11 systematic reviews. Forty pieces of best evidence in five aspects of assessment/screening, prevention, intervention, clinical management, and health education were summarized.Conclusions:The 40 best evidence for nonpharmacological management of CIPN summarized can be used to prevent or reduce CIPN in cancer patients. Clinical medical and nursing staff should select evidence entries as appropriate for different clinical situations, taking into account the patient's own condition and the feasibility and appropriateness of evidence implementation.

Objective:To analyze the clinic effects of arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint (CMCJ) Eaton stage II/III arthrosis.Methods:A retrospective study was conducted on a total of 15 cases (16 hands) of patients including 5 males (1 bilateral) and 10 females with CMCJ stage II/III arthrosis who underwent surgical treatment at the first affiliated hospital of Shenzhen university from January 2020 to June 2022, with mean age of 56.7±6.4 years (range, 46-75 years). The duration from pain to treatment was 7.8±3.2 months (range, 4-14 months). X-ray showed narrowing of CMCJ with osteophytes and distal radial subluxation. All the patients were treated with arthroscopic partial trapeziectomy and suture button suspensionplasty. The preoperative and last postoperative follow-up radiographs, visual analogue scale (VAS), thumb's Kapandji scores, disabilies of the arm, shoulder, and hand (DASH) scores, grip and pinch strength and time to return to work were compared.Results:All cases were followed up for 19.6±6.3 months (range, 11-36 months). The postoperative X-ray showed all the CMCJs were reduced with a normal height of first metacarpal. The mean time for patients to return to their daily activities was 18.69±3.70 d and the mean time to return to work was 24.63±4.91 d. The average VAS score decreased from 6.56±1.15 preoperatively to 1.00 (0.75, 1.25). The preoperative Kapandji's score was 8.00±0.82 and the postoperative Kapandji's score was 8.00 (7.25, 9.00). The average DASH values improved from 24.06±3.19 to 4.00 (3.00, 5.00). The were significant differences except for Kapandji score ( Z=-4.905, P<0.001; Z=-0.121, P=0.905; Z=-4.846, P<0.001). The mean grip and pinch strength showed improvement from an average of 16.4 (14.13, 18.68) kg and 1.70±0.35 kg to 26.14±3.27 kg and 3.58±0.91 kg with significant difference ( Z=-4.617, P<0.001; t=-7.669, P<0.001). Conclusion:Arthroscopic partial trapeziectomy and suture button suspensionplasty is a minimally invasive surgery for the treatment of first CMCJ Eaton stage II/III arthrosis. By this technique, the patients' existing instability and pain problems can be solved.

Objective:To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle between gonadotropin-releasing hormone (GnRH) antagonist protocol and progestin-primed ovarian stimulation (PPOS) protocol in patients aged 20-50 years.Methods:A retrospective cohort study was conducted to analyze 3 752 infertile patients aged 20-50 years who received in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). They used either GnRH antagonist protocol or PPOS protocol at the Center of Assisted Reproduction in Shanghai First Maternity and Infant Hospital from January 2017 to April 2021. One to one propensity score matching (PSM) was used to match the population characteristics. Baseline, clinical and laboratory characteristics, as well as pregnancy outcomes were compared between the two groups. The differences of CLBR was analyzed by multivariate logistic regression and subgroup analysis. Results:After matching, 1 466 patients (733 in each group) were included in the analysis. No significant differences were detected in age, body mass index, infertility type, cause and duration of infertility, number of stimulation cycles, basal follicle-stimulating hormone, number of antral follicles and composition ratio of insemination methods between the two groups ( P>0.05). Serum estradiol level [1 700.30 (1 011.76, 2 580.50) ng/L] and luteinizing hormone (LH) level [1.95 (1.07, 5.27) U/L] on trigger day were significantly lower in GnRH antagonist group than in PPOS group [2 056.50 (884.08, 3 601.59) ng/L, P=0.010; 3.00 (1.51, 5.00) U/L, P<0.001]. The cycle cancellation rate of PPOS group [30.56% (224/733)] was significantly higher than that of GnRH antagonist group [18.83% (138/733), P<0.001]. The numbers of oocytes obtained, available embryos and good-quality embryos were similar to those in GnRH antagonist group (all P>0.05). For each embryo transfer cycle, the implantation rate [16.97% (207/1 220) vs. 21.42% (266/1 242)], the clinical pregnancy rate [21.78% (188/863) vs. 27.38% (233/851)], the onging pregnancy rate [16.11% (139/863) vs. 21.62% (184/851)] and the live birth rate [15.06% (130/863) vs. 20.80% (177/851)] were significantly lower in PPOS group than in GnRH antagonist group ( P=0.010, P=0.012, P=0.004 and P=0.002, respectively). The CLBR of PPOS group was significantly lower than that of GnRH antagonist group [17.74% (130/733) vs. 24.15% (177/733), P=0.003]. Multivariate logistic regression analysis showed that ovarian stimulation protocol was an independent risk factor for CLBR [ OR=1.42, 95% CI: 1.03-1.95, P=0.032]. The results of subgroup analysis showed that the CLBR of PPOS group was significantly lower than that of GnRH antagonist group in the population aged ≤35 years and underwent non-first IVF/ICSI cycle [21.35% (111/520) vs. 28.93% (151/522), P=0.005; 7.85% (41/522) vs. 12.23% (62/507), P=0.019]. Conclusion:Compared with PPOS regimen, antagonist regimen can improve the CLBR per oocyte cycle in infertile patients aged 20-50 years, and is more significant in women aged ≤35 years and non-first oocyte collection patients.

Objective:To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle between gonadotropin-releasing hormone (GnRH) antagonist protocol and progestin-primed ovarian stimulation (PPOS) protocol in patients aged 20-50 years.Methods:A retrospective cohort study was conducted to analyze 3 752 infertile patients aged 20-50 years who received in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). They used either GnRH antagonist protocol or PPOS protocol at the Center of Assisted Reproduction in Shanghai First Maternity and Infant Hospital from January 2017 to April 2021. One to one propensity score matching (PSM) was used to match the population characteristics. Baseline, clinical and laboratory characteristics, as well as pregnancy outcomes were compared between the two groups. The differences of CLBR was analyzed by multivariate logistic regression and subgroup analysis. Results:After matching, 1 466 patients (733 in each group) were included in the analysis. No significant differences were detected in age, body mass index, infertility type, cause and duration of infertility, number of stimulation cycles, basal follicle-stimulating hormone, number of antral follicles and composition ratio of insemination methods between the two groups ( P>0.05). Serum estradiol level [1 700.30 (1 011.76, 2 580.50) ng/L] and luteinizing hormone (LH) level [1.95 (1.07, 5.27) U/L] on trigger day were significantly lower in GnRH antagonist group than in PPOS group [2 056.50 (884.08, 3 601.59) ng/L, P=0.010; 3.00 (1.51, 5.00) U/L, P<0.001]. The cycle cancellation rate of PPOS group [30.56% (224/733)] was significantly higher than that of GnRH antagonist group [18.83% (138/733), P<0.001]. The numbers of oocytes obtained, available embryos and good-quality embryos were similar to those in GnRH antagonist group (all P>0.05). For each embryo transfer cycle, the implantation rate [16.97% (207/1 220) vs. 21.42% (266/1 242)], the clinical pregnancy rate [21.78% (188/863) vs. 27.38% (233/851)], the onging pregnancy rate [16.11% (139/863) vs. 21.62% (184/851)] and the live birth rate [15.06% (130/863) vs. 20.80% (177/851)] were significantly lower in PPOS group than in GnRH antagonist group ( P=0.010, P=0.012, P=0.004 and P=0.002, respectively). The CLBR of PPOS group was significantly lower than that of GnRH antagonist group [17.74% (130/733) vs. 24.15% (177/733), P=0.003]. Multivariate logistic regression analysis showed that ovarian stimulation protocol was an independent risk factor for CLBR [ OR=1.42, 95% CI: 1.03-1.95, P=0.032]. The results of subgroup analysis showed that the CLBR of PPOS group was significantly lower than that of GnRH antagonist group in the population aged ≤35 years and underwent non-first IVF/ICSI cycle [21.35% (111/520) vs. 28.93% (151/522), P=0.005; 7.85% (41/522) vs. 12.23% (62/507), P=0.019]. Conclusion:Compared with PPOS regimen, antagonist regimen can improve the CLBR per oocyte cycle in infertile patients aged 20-50 years, and is more significant in women aged ≤35 years and non-first oocyte collection patients.

Objective:To investigate the effect of preimplantation genetic testing for aneuploidies (PGT-A) based on next-generation sequencing technology (NGS) on the clinical outcomes of patients with recurrent implantation failure (RIF).Methods:A retrospective cohort study was conducted and the outcomes of patients with a history of RIF were analyzed, of which 63 women underwent PGT-A strategy (study group) and 179 women who underwent conventional in vitro fertilization (IVF) treatment (control group) at the Centre of Assisted Reproduction in Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine from December 2018 to January 2020. Propensity score matching (PSM) was conducted by female age. Baseline characteristics, stimulation characteristics and pregnancy outcomes were analyzed between the two groups. Logistic regression model was used to evaluate the relative prognostic significance of independent variables in relation to the live birth rate (LBR) and cumulative live birth rate (CLBR). Results:Totally 203 patients including 61 patients in study group and 142 patients in control group remained in each group after PSM, there were no significant differences in female age, body mass index, cause of infertility, duration of infertility, number of previous embryo transfer failures, basal follicle-stimulating hormone (bFSH), antral follicle count and ovarian stimulation protocols after matching (all P>0.05). More patients had unavailable embryos in study group than in control group [45.90% (28/61) vs. 13.38% (19/142), P<0.001], while the number of transferable embryos was significantly lower than that in control group [1(0, 2) vs. 2(1, 4), P<0.001]. The implantation rate [61.54% (24/39)], the clinical pregnancy rate [61.54% (24/39)], the ongoing pregnancy rate [61.54% (24/39)] and the live birth rate [61.54% (24/39)] per embryo transfer cycle in study group were significantly higher than those in control group [27.47% (75/273), P<0.001; 41.51% (66/159), P=0.024; 37.11% (59/159), P=0.006 and 37.11% (59/159), P=0.006, respectively]. However, there was no significant difference in CLBR between the two groups [39.34% (24/61) vs. 41.55% (59/142), P=0.770]. Logistic regression revealed that women used PGT was 2.71 times more likely to achieve live birth per transfer cycle compared with those women used non-PGT [ OR (95% CI) =2.71(1.32-5.58), P=0.007], however, the use of PGT was not associated with CLBR [ OR (95% CI)=2.49(0.87-7.13), P=0.089]. Conclusion:Compared with conventional IVF treatment, NGS-PGT strategy can improve the live birth rate per embryo transfer cycle, but cannot improve the cumulative live birth rate in RIF patients. Therefore, the clinical value of NGS-PGT strategy in RIF patients is still debatable.

Objective:To investigate the effect of preimplantation genetic testing for aneuploidies (PGT-A) based on next-generation sequencing technology (NGS) on the clinical outcomes of patients with recurrent implantation failure (RIF).Methods:A retrospective cohort study was conducted and the outcomes of patients with a history of RIF were analyzed, of which 63 women underwent PGT-A strategy (study group) and 179 women who underwent conventional in vitro fertilization (IVF) treatment (control group) at the Centre of Assisted Reproduction in Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine from December 2018 to January 2020. Propensity score matching (PSM) was conducted by female age. Baseline characteristics, stimulation characteristics and pregnancy outcomes were analyzed between the two groups. Logistic regression model was used to evaluate the relative prognostic significance of independent variables in relation to the live birth rate (LBR) and cumulative live birth rate (CLBR). Results:Totally 203 patients including 61 patients in study group and 142 patients in control group remained in each group after PSM, there were no significant differences in female age, body mass index, cause of infertility, duration of infertility, number of previous embryo transfer failures, basal follicle-stimulating hormone (bFSH), antral follicle count and ovarian stimulation protocols after matching (all P>0.05). More patients had unavailable embryos in study group than in control group [45.90% (28/61) vs. 13.38% (19/142), P<0.001], while the number of transferable embryos was significantly lower than that in control group [1(0, 2) vs. 2(1, 4), P<0.001]. The implantation rate [61.54% (24/39)], the clinical pregnancy rate [61.54% (24/39)], the ongoing pregnancy rate [61.54% (24/39)] and the live birth rate [61.54% (24/39)] per embryo transfer cycle in study group were significantly higher than those in control group [27.47% (75/273), P<0.001; 41.51% (66/159), P=0.024; 37.11% (59/159), P=0.006 and 37.11% (59/159), P=0.006, respectively]. However, there was no significant difference in CLBR between the two groups [39.34% (24/61) vs. 41.55% (59/142), P=0.770]. Logistic regression revealed that women used PGT was 2.71 times more likely to achieve live birth per transfer cycle compared with those women used non-PGT [ OR (95% CI) =2.71(1.32-5.58), P=0.007], however, the use of PGT was not associated with CLBR [ OR (95% CI)=2.49(0.87-7.13), P=0.089]. Conclusion:Compared with conventional IVF treatment, NGS-PGT strategy can improve the live birth rate per embryo transfer cycle, but cannot improve the cumulative live birth rate in RIF patients. Therefore, the clinical value of NGS-PGT strategy in RIF patients is still debatable.

Background/Aims: We aimed to study the clinical characteristics, treatment modality, and the prognosis of synchronous multiple primary esophageal squamous cell carcinomas (SMPESCC). Methods: A total of 117 SMPESCC cases were evaluated retrospectively from 2010 to 2015. Results: The most common locations of SMPESCC were mid- and lower thoracic segments (n = 208, 84.9%). The 1-, 2-, and 3-year overall survival rates were 53.8%, 30.8%, and 15.4%, respectively; the median survival time (MST) was 12.5 months. With definitive radiotherapy and surgery, respectively, the MST of stage I/II patients were 34.2 and 26.7 months, of stage III patients were 8.3 and 13.2 months (p = 0.163), and of stage IV patients were and 8 and 12.6 months (p = 0.379). Clinical stage, family history of cancer, and Karnofsky performance status were independent prognostic factors for the whole cohort by Cox multivariate regression analysis (hazard ratio [HR] = 0.859, p < 0.001; HR = 0.579, p = 0.032; and HR = 0.586, p = 0.013). Conclusions Although the prognosis of SMPESCC is poor, stage I/II patients can achieve long-term survival with aggressive treatment, especially those with a Karnofsky performance score 90 or higher and who have no family history of cancer. Definitive radiotherapy could achieve a similar survival rate to definitive surgery at different clinical stages.