Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemoradiotherapy ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Prospective Studies ; Rectal Neoplasms/pathology* ; Thrombocytopenia/drug therapy* ; Treatment Outcome ; Adult ; Aged

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

Background:: Visual-spatial neglect (VSN) is a neuropsychological syndrome, and right-hemisphere stroke is the most common cause. The pathogenetic mechanism of VSN remains unclear. This study aimed to investigate the behavioral and event-related potential (ERP) changes in patients with or without VSN after right-hemisphere stroke. Methods:: Eleven patients with VSN with right-hemisphere stroke (VSN group) and 11 patients with non-VSN with righthemisphere stroke (non-VSN group) were recruited along with one control group of 11 age- and gender-matched healthy participants. The visual-spatial function was evaluated using behavioral tests, and ERP examinations were performed. Results:: The response times in the VSN and non-VSN groups were both prolonged compared with those of normal controls (P < 0.001). In response to either valid or invalid cues in the left side, the accuracy in the VSN group was lower than that in the non-VSN group (P < 0.001), and the accuracy in the non-VSN group was lower than that in controls (P < 0.05). The P1 latency in the VSN group was significantly longer than that in the control group (F[2, 30] = 5.494, P = 0.009), and the N1 amplitude in the VSN group was significantly lower than that in the control group (F[2, 30] = 4.343, P = 0.022). When responding to right targets, the lefthemisphere P300 amplitude in the VSN group was significantly lower than that in the control group (F[2, 30] = 4.255, P = 0.025). With either left or right stimuli, the bilateral-hemisphere P300 latencies in the VSN and non-VSN groups were both significantly prolonged (all P < 0.05), while the P300 latency did not differ significantly between the VSN and non-VSN groups (all P > 0.05). Conclusions: Visual-spatial attention function is impaired after right-hemisphere stroke, and clinicians should be aware of the subclinical VSN. Our findings provide neuroelectrophysiological evidence for the lateralization of VSN.

OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min•1.73 m, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min•1.73 m, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min•1.73 m per year. CONCLUSION Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).
Adult ; Disease Progression ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; drug effects ; Humans ; Kidney Diseases ; drug therapy ; physiopathology ; Male ; Middle Aged ; Outcome Assessment (Health Care)

BACKGROUND: Visual-spatial neglect (VSN) is a neuropsychological syndrome, and right-hemisphere stroke is the most common cause. The pathogenetic mechanism of VSN remains unclear. This study aimed to investigate the behavioral and event-related potential (ERP) changes in patients with or without VSN after right-hemisphere stroke. METHODS: Eleven patients with VSN with right-hemisphere stroke (VSN group) and 11 patients with non-VSN with right-hemisphere stroke (non-VSN group) were recruited along with one control group of 11 age- and gender-matched healthy participants. The visual-spatial function was evaluated using behavioral tests, and ERP examinations were performed. RESULTS: The response times in the VSN and non-VSN groups were both prolonged compared with those of normal controls (P < 0.001). In response to either valid or invalid cues in the left side, the accuracy in the VSN group was lower than that in the non-VSN group (P < 0.001), and the accuracy in the non-VSN group was lower than that in controls (P < 0.05). The P1 latency in the VSN group was significantly longer than that in the control group (F[2, 30] = 5.494, P = 0.009), and the N1 amplitude in the VSN group was significantly lower than that in the control group (F[2, 30] = 4.343, P = 0.022). When responding to right targets, the left-hemisphere P300 amplitude in the VSN group was significantly lower than that in the control group (F[2, 30] = 4.255, P = 0.025). With either left or right stimuli, the bilateral-hemisphere P300 latencies in the VSN and non-VSN groups were both significantly prolonged (all P < 0.05), while the P300 latency did not differ significantly between the VSN and non-VSN groups (all P > 0.05). CONCLUSIONS Visual-spatial attention function is impaired after right-hemisphere stroke, and clinicians should be aware of the subclinical VSN. Our findings provide neuroelectrophysiological evidence for the lateralization of VSN.
Adult ; Aged ; Cerebral Infarction ; physiopathology ; Electrophysiology ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Nitric Oxide Synthase Type III ; genetics ; PPAR gamma ; genetics ; Perceptual Disorders ; genetics ; metabolism ; physiopathology ; Polymorphism, Genetic ; genetics ; Reaction Time ; genetics ; physiology ; Reactive Oxygen Species ; metabolism ; Stroke ; genetics ; metabolism ; physiopathology ; Superoxide Dismutase ; genetics

OBJECTIVETo investigate the factors associated with the occurrence of transplant renal artery stenosis (TRAS).

METHODSA retrospective analysis was conducted in 26 recipients who developed TRAS and 40 concurrent renal recipients without TRAS. We also conducted a nested case-control study in 14 patients with TRAS (TRAS-SD group) and another 14 non-TRAS recipients who received the allograft from the same donor (non-TRAS-SD group).

RESULTSCompared with those in the concurrent recipients without TRAS, acute rejection (AR) occurred at a significantly higher incidence (P=0.004) and the warm ischemia time (WIT) was significantly longer (P=0.015) and the level of high?density lipoprotein cholesterol (HDL--C) significantly lower (P=0.009) in the recipients with TRAS. Logistic regression analysis suggested that AR (P=0.007) and prolonged WIT (P=0.046) were risk factors of TRAS while HDL-C (P=0.022) was the protective factor against TRAS. In recent years early diagnosis of TRAS had been made in increasing cases, the interval from transplantation to TRAS diagnosis became shortened steadily, and the recipients tended to have higher estimated glomerular filtration rate at the time of TRAS diagnosis.

CONCLUSIONApart from the surgical technique, AR and prolonged WIT are also risk factors of TRAS while a high HDL-C level is the protective factor against TRAS. The improvement of the diagnostic accuracy by ultrasound is the primary factor contributing to the increased rate of early TRAS diagnosis in recent years.

This study aimed to investigate the prevalence and molecular characteristics of Listeria monocytogenes in cooked products in Zigong City, China. The overall occurrence of the L. monocytogenes in the ready-to-eat (RTE) shops and mutton restaurants surveyed was 16.2% (141/873). An occurrence of 13.5% was observed in RTE pork, 6.5% in RTE vegetables, and more than 24.0% in either cooked mutton or cooked haggis. Serotype 1/2b (45.4%), 1/2a (33.3%), and 1/2c (14.2%) were the predominant types. By comparing the clonal complexes (CCs) based on multilocus sequence typing (MLST) of the L. monocytogenes from cooked foods in Zigong City and 33 listeriosis cases from different districts of China, CC87, CC9, CC8, and CC3 were showed to be prevalent in cooked products and CC87 and CC3 were the first two frequent types in the 33 clinic-source strains. All CC87 stains harbored the newly reported Listeria pathogenicity island 4 (LIPI-4) gene fragment ptsA, and all CC3 strains possessed the Listeria pathogenicity island 3 (LIPI-3) gene fragment llsX. These may increase the occurrence of the strains belonging to CC87 and CC3 in listeriosis cases in China and also underline the risk of infection owing to the consumption of the cooked products from Zigong. ST619 (serotype 1/2b) harbored both llsX and ptsA, indicating a potential hypervirulent sequence type in Zigong.
China ; epidemiology ; Cooking ; Fast Foods ; microbiology ; Food Contamination ; Food Microbiology ; Humans ; Listeria monocytogenes ; genetics ; pathogenicity ; Listeriosis ; epidemiology ; microbiology ; Meat ; microbiology ; Multilocus Sequence Typing ; Prevalence ; Seasons

BACKGROUND: Studies have shown that bone marrow mesenchymal stem cells have the potential of differentiation into alveolar epithelial cells in vitro, but so far no study has indicated that adipose-derived mesenchymal stem cells (ADSCs) can be differentiated into alveolar epithelial cells through long-term Transwell co-culture. OBJECTIVE: To observe whether rat lung epithelial-T-antigen negative cell lines (RLE-6TN) can induce rat ADSCs to differentiate into type II alveolar epithelial cells by long-term Transwell co-culture. METHODS: Three SPF health female Sprague-Dawley rats were used as donors to separate, extract, culture and identity ADSCs. The experimental group was subjected to the Transwell co-culture of ADSCs and RLE-6TN, while the control group was subjected to the culture of ADSCs alone. The morphological changes of ADSCs were observed by the inverted phase contrast microscope at 21 days after co-culture. Immunofluorescence staining using surfactant protein C (SP-C) was performed on the co-cultured ADSCs. The fluorescence staining was observed using the inverted fluorescence microscope. Integral optical density (IOD) analysis was conducted by Image pro plus 6.0 software. RESULTS AND CONCLUSION: RLE-6TN cells were identified by fluorescence staining with stable expression of SP-C protein (red fluorescence) in the experimental group, and there was no red fluorescence in the control group. After 21-day co-culture, the cell shape in the experimental group was transformed from the long spindle shape into oval or polygon shape gradually, while the cell shape in the control group remained fibroblast-like. These results show that RLE-6TN can induce ADSCs to differentiate into type II alveolar epithelial cells after a long-term (21 days) co-culture.

Background:Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course,and available treatments for delaying the progression to end-stage renal disease are limited.This study aimed to assess the efficacy and safety of the traditional Chinese medicine,Niaoduqing particles,for delaying renal dysfunction in patients with stage 3b-4 CKD.Methods:The present study was a prospective,randomized,double-blind,placebo-controlled,multicenter clinical trial.From May 2013 to December 2013,300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml,min-1· 1.73 m-2,aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces.Patients were randomized in a 1∶1 ratio to either a test group,which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks,or a control group,which was administered a placebo using the same methods.The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment.The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test.The present study reported results based on an intention-to-treat (ITT) analysis.Results:A total of 292 participants underwent the ITT analysis.At 24 weeks,the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the test and control groups,respectively (Z =2.642,P =0.008),and the median change in eGFR was-0.2 (-4.3-2.7) and-2.2 (-5.7-0.8) ml·min-1.1.73 m-2,respectively (Z =-2.408,P =0.016).There were no significant differences in adverse events between the groups.Conclusions:Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD.This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction.