Objective:To explore the dosimetric advantages of 3D printed individualized molds in assisting postoperative three-dimensional brachytherapy (3D BT) for endometrial cancer.Methods:The 3D BT plans of 21 postoperative patients with early-stage endometrial cancer at the First Affiliated Hospital of Ningbo University were retrospectively selected as the individualized mold group (the mold group). On this basis, virtual single-channel cylindrical applicator plans that employed a 3D inverse simulated annealing algorithm were designed for all the patients using the Beijing Colins Planning System (the single-channel group). Comparisons were made between the two groups of plans regarding the minimum doses exposed to 90%, 98%, and 100% of target area ( D90, D98, and D100), conformity index (CI), homogeneity index (HI), and overdose index (OI), as well as the maximum doses exposed to 0.01, 1, 2, and 5 cm 3organs at risk (bladder, rectum, small intestine, and urethra) ( D0.01 cm 3, D1 cm 3, D2 cm 3, and D5 cm 3). Results:Both groups met clinical requirements. For doses to target volumes, there was no significant difference in D90, D98, and D100 between both groups, with the mold group demonstrating superior CI and HI but lower OI compared to the single-channel group ( t = -3.21, -5.99, 6.25, P < 0.05). Concerning the doses exposed to organs at risk, the mold group displayed significantly reduced D1 cm 3, D2 cm 3, and D5 cm 3 for the bladder, rectum, and urethra compared to the single-channel group ( t = 3.18, 3.21, 3.77, 7.97, 8.92, 10.92, 2.54, 3.46, 4.28, P < 0.05). There was no significant difference in the doses exposed to the small intestine between both groups ( P > 0.05) due to the large distance from the small intestine to the target volumes. Conclusions:3D printed individualized molds exhibit advantages in terms of the homogeneity and conformity indices of target volumes in postoperative three-dimensional brachytherapy for endometrial cancer, accompanied by low doses exposed to the bladder, rectum, and urethra, thereby holding the potential for broader application.

Objective:To identify the dosimetric and radiobiological differences of three radiotherapy techniques of whole breast irradiation with simultaneous integrated boost (WBI-SIB) following breast-conserving surgery for early breast cancer (EBC).Methods:The data of 20 patients with early left-sided breast cancer who received radiotherapy following breast-conserving surgery were retrospectively analyzed. Three radiotherapy techniques, namely hybrid intensity-modulated radiotherapy (HIMRT), intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT), were redesigned with the same prescription dose and target conditions. Then, doses to target volume (TV) and organs at risk (OAR), along with the normal tissue complication probability (NTCP) and secondary cancer risk (SCR) for specific organs, were compared.Results:Compared to HIMRT and IMRT, VMAT led to significant decreases in various dosimetric indices of the affected lung and heart and increases in the Dmean doses to the healthy lung and healthy breast and V5 Gy doses to the healthy breast, with the differences being significantly different ( P < 0.05). The average NTCP values of cardiac death, radiation pneumonitis, and pulmonary fibrosis induced by VMAT were 0.41%, 1.62%, and 23.59%, respectively, significantly lower than those caused by other two techniques ( P < 0.05). No statistical differences were found in 10 dosimetric indices of OAR between IMRT and HIMRT, while the NTCP analysis suggested that the risks of cardiac death ( t = 2.70, P < 0.05) and pulmonary fibrosis ( t =4.11, P < 0.05) induced by IMRT were slightly lower than those caused by HIMRT. In addition, the excess absolute risk (EAR) to the healthy lung posed by VMAT was 1.65 and 1.83 times those induced by HIMRT and IMRT, respectively ( z = -3.92, t = -6.43, P < 0.05). In contrast, the EAR to the healthy breast induced by VMAT was 2.79 and 2.65 times those posed by HIMRT and IMRT, respectively ( z = -3.21, -3.70, P < 0.05). Conclusions:Among three intensive-modulated radiotherapy techniques of WBI-SIB for EBC, VMAT provides the optimal protection for the heart and affected lung but leads to the highest SCR to the healthy lung and breast. When VMAT is employed for young EBC patients or those with normal cardiopulmonary function, special attention should be paid to reducing low-dose irradiations to the healthy breast and thereby minimizing SCR. In contrast, VMAT might be more favorable for patients with pronounced cardiopulmonary risks or aged patients.

Objective:To assess the susceptibility of gonococcal clinical isolates to gentamicin in Guangxi region, China, and to analyze the correlation between the minimum inhibitory concentration (MIC) of gentamicin and MICs of 7 other antibiotics.Methods:From December 2020 to December 2021, 584 gonococcal clinical isolates were collected from 37 medical institutions in 14 prefecture-level cities in Guangxi region. The susceptibility of gonococcal clinical isolates to ceftriaxone, cefixime, azithromycin, spectinomycin, penicillin, tetracycline, ciprofloxacin and gentamicin was determined by using an agar dilution method. The MIC values of antibiotics were logarithmically transformed with base 2, and Spearman correlation analysis was carried out to evaluate the correlation between the MIC of gentamicin and MICs of the other 7 antibiotics.Results:The MIC of gentamicin ranged from 1 to 16 mg/L, and the MIC50 and MIC90 values were 4 and 8 mg/L, respectively; 361 strains (61.8%) were fully sensitive to gentamicin with the MIC ≤ 4 mg/L, 223 strains (38.2%) moderately sensitive with the MIC ranging from 8 to 16 mg/L, and no gentamicin-resistant strains were found. The number of strains resistant to azithromycin, penicillin, tetracycline and ciprofloxacin was 136 (23.3%), 415 (71.1%), 339 (58.0%) and 574 (98.3%) respectively, the number of lowly sensitive strains to ceftriaxone and cefixime was 17 (2.9%) and 6 (1.0%) respectively, and no spectinomycin-resistant strains were found. Spearman correlation analysis showed that the MIC of gentamicin was weakly correlated with the MICs of azithromycin, spectinomycin, penicillin, tetracycline, and ciprofloxacin (all P < 0.05), but was uncorrelated with the MICs of ceftriaxone and cefixime (both P > 0.05) . Conclusion:All gonococcal clinical isolates tested in this study showed a certain degree of susceptibility to gentamicin, and cross-resistance between gentamicin and other antibiotics was less likely to occur.

Objective:To compare three fixed-field intensity-modulated radiotherapy (IMRT) plans for nasal cavity and paranasal sinus tumors, including the coplanar IMRT (C-IMRT) plan and the non-coplanar IMRT(NC-IMRT) plan which were based on a conventional C-arm LINAC (Trilogy), and the coplanar IMRT (H-IMRT) plan based on an O-ring LINAC (Halcyon).Methods:Based on the data of 10 patients in the Ningbo First Hospital from December 2018 to December 2021 with nasal cavity and paranasal sinus tumors who underwent postoperative radiotherapy, this study redesigned three IMRT plans with the same prescribed doses and optimization objectives. Then, this study compared the doses of target volumes and organ at risks(OARs), the validation pass rates, and the execution time of these plans. Friedman test was employed in this study, and multiple comparisons were further made in cases of different results.Results:The differences in the conformal index (CI) of PTV and PTV boost of the three plans were statistically significant ( χ2 = 7.51, 9.69, P < 0.05). The multiple comparisons showed that the median CI of the H-IMRT plan was higher than that of the NC-IMRT plan ( Z = 2.53, 2.68, P < 0.05). The differences in other parameters of target volumes were not statistically significant. Compared with the C-IMRT plan, the H-IMRT plan reduced the Dmax of bilateral lenses, bilateral corneas, ipsilateral optic nerve, and ipsilateral eyeball ( Z = 2.80, 2.80, 2.80, 2.80, 2.81, 2.09, P < 0.05). Compared with the C-IMRT plan, the NC-IMRT reduced the Dmax of bilateral lenses, corneas, and eyeballs and contralateral optic nerve ( Z = 2.80, 2.66, 2.80, 2.70, 2.29, 2.29, 2.65, P < 0.05) and reduced the Dmean of bilateral eyeballs ( Z = 2.80, 2.80, P < 0.05). Compared with the NC-IMRT plan, the H-IMRT plan reduced the Dmax of the ipsilateral lens and cornea ( Z = 2.50, 2.08, P < 0.05), but increased the Dmax of the contralateral optic nerve and the Dmean of bilateral eyeballs ( Z = 2.80, 2.80, 2.80, P < 0.05). The validation pass rate of the three plans met the institutional standards, and the differences were not statistically significant. Moreover, the H-IMRT plan had the shortest median execution time (172.00 s), followed by the C-IMRT plan (337.50 s), and the NC-IMRT plan (388.00 s). Conclusions:The verification pass rate of the three plans can achieve the requirements of treatment implementation. The three plans had similar dosimetric differences in target volumes. However, the H-IMRT and NC-IMRT plans can protect the normal tissues (especially optical organs) more effectively than the C-IMRT plan, which is conducive to reducing the toxicity after radiotherapy and provides space for local dose increase or the radiotherapy for the treatment of tumor recurrence. The execution efficiency of the three plans is in the order of H-IMRT > C-IMRT > NC-IMRT. It is necessary to select appropriate radiotherapy equipment and technology according to actual situations.

Clinicopathological data of 15 patients with pyloric early cancer and precancerous lesions, who received endoscopic submucosal dissection (ESD) in Zhejiang Cancer Hospital from March 2011 to January 2020 were retrospectively analyzed. Postoperative pathology showed 7 cases of low-grade intraepithelial neoplasia, 3 cases of high-grade intraepithelial neoplasia, and 5 cases of early gastric cancer. R0 complete resection was achieved in all patients. The mean operation time was 55.2 min (35-78 min). One patient had delayed postoperative bleeding, and no other complications such as bleeding, perforation or abdominal pain occurred in other 14 patients. No recurrence, metastasis or pyloric stenosis was found during the follow-up of 31.3 months (1-106 months). ESD is safe and effective for early cancer and precancerous lesions in the pylorus.

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.
Adenosine Monophosphate/therapeutic use* ; Alanine/therapeutic use* ; Alveolar Epithelial Cells/virology* ; Antibodies, Neutralizing/therapeutic use* ; COVID-19/virology* ; Down-Regulation ; Drug Discovery ; Human Embryonic Stem Cells/metabolism* ; Humans ; Immunity ; Lipid Metabolism ; Lung/virology* ; RNA, Viral/metabolism* ; SARS-CoV-2/physiology* ; Virus Replication/drug effects*

Objective:To explore the safety and efficiency of a novel bipolar electric knife for endoscopic submucosal dissection.Methods:The thermal damage on tissue caused by the new bipolar knife and traditional monopolar knife were compared by finite element analysis. The vertical thermal damage to the porcine gastric wall caused by the two types of electric knife were analyzed in vitro animal experiments. In vivo animal experiments were used to compare operation related indexes of two types of electric knife, including en bloc resection rate and cutting efficiency in porcine digestive tract submucosal dissection. Results:Through overcoming deviation of experimental individuals and operator experience, the finite element model showed that the length, width and depth of thermal damage on tissue caused by the monopolar knife was 1.08 times, 1.12 times, and 1.23 times of that of the bipolar knife, respectively. Additionally, the bipolar knife caused less vertical thermal damage to the porcine gastric wall than the monopolar knife (433.25±42.58 μm VS 898.03±111.59 μm, t=6.740, P=0.003) in vitro animal experiments when charged for 1 s at the same power. Finally, in vivo animal experiments showed that the en bloc resection rates of the two kinds of electric knife systems were both 100.0%. In addition, the cutting area and cutting time of the bipolar knife was 229.58±185.29 mm 2 and 164.37±96.27 s, respectively. The corresponding indicators of the monopolar knife was 209.70±167.35 mm 2 and 162.65±69.97 s, respectively, and there was no significant difference (all P>0.05). Conclusion:The novel bipolar knife not only ensures the cutting efficiency but also reduces the thermal damage during endoscopic submucosal dissection in simulating experiment and animal experiment, which needs further verification in clinical trial.

In China,peritoneal metastasis of gastric cancer has main characteristics of high incidence,late staging and poor prognosis.However,the proposal of conversion therapy has brought hope to patients.Conversion therapy of peritoneal metastasis in gastric cancer is a novel concept,which aims at down-staging of the gastric cancer's primary lesion and effectively controlling the peritoneal metastases at the same time through valid chemotherapy and other means.Then the surgeons strive for performing radical gastrectomy and lymph node dissection (D2) to prolong survival time of the patients with advanced gastriccancer and improve their life quality.Systemic chemotherapy is the core of the methods of conversion therapy,while the local intraperitoneal chemotherapy can be used as a supplement.Neoadjuvant intraperitoneal-systemic chemotherapy (NIPS) is the most promising technique as conversion therapy due to the comprehensive advantages of the systemic chemotherapy and local intraperitoneal chemotherapy.In recent years,there were many clinical studies reporting NIPS for conversion therapy of peritoneal metastasis in gastric cancer.Therefore,this paper systematically reviews experiences of clinical application in order to provide references for clinical practice of conversion therapy in gastric cancer.

Objective To apply 3D printing technology to fabricate patient-specific silicone tissue compensators for the chest wall and compare the advantages and clinical characteristics between conventional bolus and 3D-printed PLA materials. Methods The chest wall data of two breast cancer patients undergoing mastectomy were obtained based upon the CT images. A patient-specific 3D printing silicone rubber bolus (3D-SRB) was designed and fabricated. The conformability of 3D-SRB,3D-PLA and conventional bolus to the chest wall were validated. Ecipse8. 6 planning system was adopted to statistically compare the dosimetric parameters of virtual plan with those after using three tissue compensators. Results The 3D-SRB was successfully designed and fabricated with a similar hardness to conventional bolus. During the process of validating conformability and radiotherapy planning,3D-SRB and 3D-PLA were superior to conventional bolus in terms of conformability to chest wall and planning dosimetric distribution.3D-SRB was advantageous in repeatability, conformability and comfortable experience compared with 3D-PLA. Regarding dosimetric parameters,3D-SRB yielded the highest repeatability with the virtual plan, followed by 3D-PLA and conventional bolus. Conclusion It is applicable to utilize 3D-SRB as the patient-specific compensators for the chest wall,which is of significance in clinical practice.