Abstract On August 11, 2022, Tongxiang Center for Disease Control detected a case of brucellosis, and the case was not engaged in related work. Case finding and risk factor investigation were immediately conducted to trace the source of infection. It was revealed that the case sold aquatic products at a farmer's market and frequently picked up goods at a seafood warehouse adjacent to a lamb slaughtering site. There was a potential risk of infection due to indirect contact with slaughtered lambs or contaminants. Serological tests were conducted on 9 employees of the slaughtering site and 48 residents nearby, and the brucellosis cases diagnosed in hospitals in the same area were searched. A total of 11 brucellosis cases were identified, including 9 confirmed cases and 2 asymptomatic infections. There were 2 cases of slaughtering workers and 9 cases of non-occupational individuals from the surrounding area of the slaughtering site. Brucella melitensis biovar 3 were isolated from a slaughtering worker and a non-occupational individual. The slaughtered lambs primarily came from northern regions such as Inner Mongolia and Heilongjiang. It was concluded that it was a cluster caused by Brucella melitensis biovar 3 and spread through direct or indirect contact with imported infected lambs or contaminated environments from a lamb slaughtering site. It is suggested to strengthen the quarantine of imported sheep, legally shut down non-compliant lamb slaughtering sites, implement designated slaughtering and enhance occupational protection.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Objective:To evaluate the clinical effects of adjustable traction skin stretchers used in repair of wounds at the lower leg, foot and ankle.Methods:A retrospective study was performed to analyze the clinical data of 56 patients who had been treated for skin defects at the lower leg, foot and ankle from August 2016 to September 2022 at The First Affiliated Hospital of Zhengzhou University, Honghui Hospital, Affiliated to Xi'an Jiaotong University Medical College, The First Affiliated Hospital of Henan Polytechnic University, and Yunnan Zhongde Orthopedic Hospital. There were 35 males and 21 females, aged (39.9±18.7) years. There were 43 traumatic wounds, 3 burns, 6 inflammatory wounds, 3 relief incisions due to osteofascial compartment syndrome, and 1 scar. The areas of skin defect ranged from 2.5 cm × 2.0 cm to 20.0 cm × 10.0 cm. The duration of wounds was (8.6±7.8) d. All the wounds were repaired with adjustable traction skin stretchers. The row-hook type of skin stretchers was used in 28 cases, the single-rod type in 20 cases, the single-rod type combined with an external fixator in 5 cases, and a combination of the row-hook type and the single-rod type in 3 cases.The time for wound traction closure, color of wound skin margin, skin swelling around the wound, functional recovery of affected limb and complications were recorded.Results:The time from skin stretching to wound closure was (7.8±3.8) d in the 56 patients. The color of wound skin edge after stretching was normal in 16 cases, dark red in 38 cases, and dark in 2 cases; the skin swelling around the wound was degree 1 in 21 cases, degree 2 in 33 cases, and degree 3 in 2 cases. The 56 patients were followed up for (8.9±4.1) months. Primary wound closure was achieved in 48 patients, and secondary wound closure in 8 patients after repair with an autologous skin graft. Partial skin necrosis occurred due to tension blisters after skin stretching in 2 patients, one of whom was repaired with an autologous skin graft and the other of whom by dressing change. Deep bone infection recurred in 2 patients whose wounds healed after their bone defects were repaired using Ilizarov technique of bone transfer. In the 56 patients, the muscle strength of the lower extremity beyond the wound was recovered to normal, and the range of motion of the joints adjacent to the wound also recovered to normal.Conclusion:In repair of wounds at the lower leg, foot and ankle, adjustable traction skin stretchers can lead to fine clinical effects and limited complications, because the stretchers can control the tension of skin digitally and precisely.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To investigate the teaching effect of flipped classroom combined with problem-based learning (PBL) in the teaching of the Diagnostic Audiology course.Methods:A total of 72 undergraduate students majoring in audiology and speech rehabilitation in the classes of 2019 and 2020 in Chongqing Medical University were enrolled as subjects, and three chapters of the Diagnostic Audiology course were selected for teaching reform. The 34 students in the class of 2019 were enrolled as control group and received lecture-based learning (LBL), and the 38 students in the class of 2020 were enrolled as experimental group and received flipped classroom combined with PBL. The teaching effect was evaluated by comparing the two groups in terms of classroom test scores, classroom participation scores, degree of satisfaction with teaching effect, and overall satisfaction with teaching. SPSS 23.0 software was used to perform the t-test, the chi-square test, and the Mann-Whitney U test. Results:The experimental group had a significantly higher classroom test score than the control group (25.95±1.21 vs. 23.21±1.55, P<0.001). In terms of classroom participation scores, the experimental group had significantly higher scores of participation in class discussion, cooperative and collaborative abilities, and questioning skills than the control group (all P<0.001). In terms of the degree of satisfaction with teaching, compared with the control group, the experimental group had significantly higher degrees of satisfaction in the dimensions such as interest in learning, mastery of theoretical knowledge, teamwork and collaboration abilities, self-learning ability, and self-presentation ( P=0.005, 0.009, 0.001, 0.016, and 0.005). In addition, the experimental group had a significantly higher degree of overall satisfaction with teaching than the control group ( P=0.006). Conclusion:Flipped classroom combined with PBL has a good teaching effect in the Diagnostic Audiology course and thus holds promise for further application.

Objective:To investigate the characteristics of distribution and drug resistance of urinary bacteria in the mid-stream urine of patients with infectious stones.Methods:The retrospective study analyzed the clinical data of 254 patients with infectious stones in the First Affiliated Hospital of Guangzhou Medical University from September 2016 to September 2018. All patients were treated with PCNL. Overall, there were 101 male and 153 female patients, with the mean age of(51.5±12.3) years, and the mean stone burden of 1443.5(660.8, 2837.5) mm2. There were 58 (22.8%) patients with hypertension, 17(6.7%) patients with diabetes and 195(76.8%)with hydronephrosis. The mid-stream urine samples were obtained for bacterial culture and susceptibility test, and the results of urine culture and antimicrobial susceptibility were recorded and analyzed.Results:Of 254 patients involved in this study, 89(35.0%) were positive and 165 (65.0%) were negative for urinary bacterial culture of the mid-stream. The proportion of patients with positive urine bacterial culture of the mid-stream who had positive urine leucocytes, positive urine nitrite and postoperative pyrexia were 86.5%(77/89), 64.0%(57/89), 25.8%(23/89), respectively, which was higher than that of patients with negative urine bacterial culture of the mid-stream [50.3%(83/165), 14.5%(24/165), 14.5%(24/165), P<0.05]. Four teen kinds of bacteria were detected from the mid-stream urine, and the three bacteria with the highest detection rate in turn were Escherichia coli of 38.2%(34/89), Proteus mirabilis of 15.7%(14/89), and Pseudomonas aeruginosa of 11.2%(10/89). The results of this study showed that three common bacteria had high resistance to drug including Cefazolin, Cefuroxime, Cefuroxime ester, Ampicillin and Co-trimoxazole (all resistance rate>40%). The resistance rates of Escherichia coli and Pseudomonas aeruginosa to Ciprofloxacin and Levofloxacin were higher than or equal to 40%. The resistance rates of Escherichia coli and Proteus mirabilis to meropenem, imipenem, ertapenem, piperacillin/tazobactam and amikacin were all lower than 10%. In addition, the resistance rates of Escherichia coli to nitrofurantoin and tigecycline and Proteus mirabilis to tobramycin, aztreonam and cefoxitin were all less than 10%. The resistance rates of Pseudomonas aeruginosa to ceftazidime, cefepime, gentamicin and aztreonam were less than 10%. Conclusions:The highest detection rate of urinary bacteria in culture of the mid-stream with infectious stones are Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa, all of which showed high resistance to Ampicillin, Cotrimoxazole, and some cephalosporins. Escherichia coli and Pseudomonas aeruginosa showe high resistance to Ciprofloxacin and Levofloxacin, and all of the three bacteria have low resistance rates to some β-Lactamase inhibitor complex and carbapenems, suggesting a reference for clinical empirical medical treatment.

【Objective】 To analyze ABO subtype samples from tumor patients using both blood group serology and molecular biology technology. 【Methods】 32 samples of ABO subtype, identified by routine blood group serology in the Department of Transfusion, of solid tumor patients treated in Cancer Hospital of Chinese Academy of Medical Sciences from July 2014 to December 2019 were analyzed by sequence specific primer polymerase chain reaction (PCR-SSP) and gene sequencing (PCR-SBT). 5 samples were detected by PCR-SSP, 28 PCR-SBT, 1 both PCR-SSP and PCR-SBT. The serological and genotyping results were comparatively analyzed. 【Results】 66% (21/32) of the samples in this study were confirmed as ABO subtypes or harbored mutations by genotyping assays, including 7 cases of B(A).04, 2 of B(A).02, 1 of cis AB.01, 3 of BW.12, 4 of BEL.03, 1 of AEL.02, 1 of B 974G>C, 1 of A 797insT, and 1 of A 617C>G. Among the 21 subtype samples or harbored mutations, 15 had the same blood group serology and genotyping results, and 6 had no A or B antigen detected in the serological adsorption-elution test. An additional 34% (11/32) of the samples had no variants in the gene responsible for ABO subtype detected by molecular analysis. 【Conclusion】 Molecular biology techniques can assist in the identification of difficult ABO blood types caused by weakened antigens or antibodies, and subtypes in solid tumor patients, which is an important auxiliary method for accurate identification of difficult ABO blood group.

Objective:To assess the effect of stone and urine bacteria culture on the treatment of postoperative infection in percutaneous nephrolithotomy (PCNL).Methods:Between September 2016 and September 2018, 1060 patients with kidney stones treated with first-stage PCNL were included in the study. There were 614 male and 446 female patients, with the mean age (52.4±12.2) years. The mean stone burden was (1 499.6±1 435.3) mm 2. The midstream urine sample and the stone sample were sent for bacterial culture, identification of bacterial strain and antimicrobial susceptibility tests. The results of urine culture (UC), stone culture (SC) and their antimicrobial susceptibility, the details of perioperatively administered antibiotics and postoperative infections were recorded. The relationship between the postoperative infection and the SC was analyzed. Results:In 1 060 patients, 22 bacterial species were identified in UC and 52 bacterial species were identified in SC. The positive rate was higher in SC than in UC[31.8%(337/1 060)vs. 20.9%(222/1 060), P<0.001]. Escherichia coli was the most common bacteria in both UC and SC, but was more prevalent in UC than in SC [52.3%(116/222)vs. 43.6%(147/337), P<0.05]. E. coli cultured from UC and SC had high resistance to ampicillin, cefazolin, ceftriaxone, cefotaxime, levofloxacin, ciprofloxacin (all resistance rate >40%), but were sensitive to meropenem, cefoperazone/sulbactam, piperacillin/tazobactam, and amikacin (all resistance rate <10%). There was no statistical difference in the antibiotic resistance rates of E. coli from the UC and SC (all P >0.05). There were 111 (10.5%) patients who developed fever and 22 (2.1%) who developed urosepsis postoperatively. The incidences of postoperative fever and urosepsis were higher in the patients with positive SC than the patients with negative SC [23.7%(80/337)vs. 4.3%(31/723); 4.2%(14/337)vs. 1.1%(8/723), P<0.05]. Even in patients with negative UC, The incidence of postoperative fever was higher in the group with positive SC than the group with negative SC [17.9%(30/168) vs. 4.2%(28/670), P<0.05]. The incidence of postoperative fever in SC positive patients was lower if they were treated with sensitive antibiotics to the bacteria in stone than those treated with nonsensitive antibiotics [17.5%(22/126) vs. 27.5%(58/211), P<0.05]. Conclusions:The SC had high rate of culture positive, complicated bacterial species and high rate of multi-drug resistant. Positive SC was associated with increased incidence of postoperative infection even if the patients had negative UC. The SC might have a importance clinical value in the treatment of postoperative infection in PCNL.