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Objective: To investigate whether the combination of neoadjuvant hyperthermic intraperitoneal chemotherapy (NHIPEC) plus intravenous neoadjuvant chemotherapy (IV NACT) has superior efficacy to IV NACT alone. Design: Retrospective cohort study. Setting: Two tertiary referral university hospitals. Population Patients with ovarian cancer who received NACT‐interval debulking surgery (IDS) between 2012 and 2020. Methods: The tumour response to NACT was evaluated with the chemotherapy response score (CRS) system. Survival outcomes were compared. Main outcome measures: CRS 3, progression‐free survival (PFS), and overall survival (OS). Results: In total, 127 patients were included, and 46 received NHIPEC plus IV NACT. The addition of NHIPEC was independently associated with an increased likelihood of CRS 3 (p = 0.033). Patients who received NHIPEC + IV NACT had significantly improved PFS compared with those who received IV NACT alone (median PFS: 22 versus 16 months, p < 0.001). The use of NHIPEC was identified as an independent predictor of PFS (p < 0.0001). OS did not differ significantly between treatment groups (p = 0.062), although a trend favouring NHIPEC was noted. Incidence of grade 3–4 adverse events and the surgical complexity score of IDS were similar between the two groups. Conclusions: Compared with IV NACT alone, the combination of NHIPEC and IV NACT resulted in improved tumour response and longer PFS. The addition of NHIPEC did not increase the risk of adverse effects or affect the complexity of IDS. [ABSTRACT FROM AUTHOR]

Background: The chemotherapy response score (CRS) system is a reproducible prognostic tool for patients receiving neoadjuvant chemotherapy (NACT) for tubo-ovarian high-grade serous carcinoma (HGSC). Achieving CRS 3 following NACT can be used as a surrogate for progression-free survival (PFS) and overall survival (OS). This study aimed to identify predictors of CRS 3 and develop a predictive nomogram. Methods: Data were extracted from 106 HGSC patients receiving NACT. Logistic regression was used to identify independent predictors for CRS 3. A nomogram was established based on the multivariate regression model. Results: All patients received three cycles of NACT, and CRS 3 was observed in 24 (22.6%) patients. Compared with patients in the CRS 1–2 group, patients in the CRS 3 groups had significantly improved PFS (log-rank test P < 0.0001). The multivariate regression analysis identified post-NACT CA125, percent decrease in CA125, post-NACT human epididymis protein 4 (HE4), and post-NACT hemoglobin level as independent predictors of CRS 3. The Hosmer-Lemeshow test showed goodness-of-fit of this regression model (P = 0.272). The nomogram including these factors presented good discrimination (area under the curve = 0.82), good calibration (mean absolute error = 0.039), and a net benefit within the threshold probabilities of CRS 3 > 5%. Conclusions: We validated the prognostic role of the CRS system and developed a nomogram that predicts the possibility of CRS 3 following NACT. The nomogram helps to identify patients who would benefit the most from NACT. More studies are warranted to validate this model. [ABSTRACT FROM AUTHOR]

Using multiple-scale mobile gravity data in the Sichuan-Yunnan area, we systematically analyzed the relationships between spatial-temporal gravity changes and the 2014 Ludian, Yunnan Province Ms6.5 earthquake and the 2014 Kangding Ms6.3, 2013 Lushan Ms7.0, and 2008 Wenchuan Ms8.0 earthquakes in Sichuan Province. Our main results are as follows. (1) Before the occurrence of large earthquakes, gravity anomalies occur in a large area around the epicenters. The directions of gravity change gradient belts usually agree roughly with the directions of the main fault zones of the study area. Such gravity changes might reflect the increase of crustal stress, as well as the significant active tectonic movements and surface deformations along fault zones, during the period of gestation of great earthquakes. (2) Continuous significant changes of the multiple-scale gravity fields, as well as greater gravity changes with larger time scales, can be regarded as medium-range precursors of large earthquakes. The subsequent large earthquakes always occur in the area where the gravity changes greatly. (3) The spatial-temporal gravity changes are very useful in determining the epicenter of coming large earthquakes. The large gravity networks are useful to determine the general areas of coming large earthquakes. However, the local gravity networks with high spatial-temporal resolution are suitable for determining the location of epicenters. Therefore, denser gravity observation networks are necessary for better forecasts of the epicenters of large earthquakes. (4) Using gravity changes from mobile observation data, we made medium-range forecasts of the Kangding, Ludian, Lushan, and Wenchuan earthquakes, with especially successful forecasts of the location of their epicenters. Based on the above discussions, we emphasize that medium-/long-term potential for large earthquakes might exist nowadays in some areas with significant gravity anomalies in the study region. Thus, the monitoring should be strengthened. [ABSTRACT FROM AUTHOR]

Neurogenic pulmonary edema caused by severe brainstem encephalitis is the leading cause of death in young children infected by Enterovirus 71 (EV71). However, no pulmonary lesions have been found in EV71-infected transgenic or non-transgenic mouse models. Development of a suitable animal model is important for studying EV71 pathogenesis and assessing effect of therapeutic approaches. We had found neurological disorders in EV71-induced young gerbils previously. Here, we report severe pulmonary lesions characterized with pulmonary congestion and hemorrhage in a gerbil model for EV71 infection. In the EV71-infected gerbils, six 21-day-old or younger gerbils presented with a sudden onset of symptoms and rapid illness progression after inoculation with 1×105.5 TCID50 of EV71 via intraperitoneal (IP) or intramuscular (IM) route. Respiratory symptoms were observed along with interstitial pneumonia, pulmonary congestion and extensive lung hemorrhage could be detected in the lung tissues by histopathological examination. EV71 viral titer was found to be peak at late stages of infection. EV71-induced pulmonary lesions, together with severe neurological disorders were also observed in gerbils, accurately mimicking the disease process in EV71-infected patients. Passive transfer with immune sera from EV71 infected adult gerbils with a neutralizing antibody (GMT=89) prevented severe pulmonary lesion formation after lethal EV71 challenge. These results establish this gerbil model as a useful platform for studying the pathogenesis of EV71-induced pulmonary lesions, immunotherapy and antiviral drugs. [ABSTRACT FROM AUTHOR]

Summary Objectives In the winter of 2013, people were facing the risk of human-to-human transmission of the re-emerging influenza A(H7N9) virus. We report herein information on the clinical features of two patients from the same family infected with this virus, the genomic sequences of the viruses harbored, and antiviral drug sensitivity. Methods Clinical and epidemiological data of two patients from the same family were collected and analyzed. Sequencing was done for the viruses isolated from these two patients and one epidemiologically related chicken, and the sequences of the eight gene segments of the viruses were analyzed phylogenetically. The sensitivity of the viruses to antiviral drug treatment was determined by neuraminidase inhibitor susceptibility test. Results The two patients from one family cluster shared the same symptoms but had different outcomes, and had a strong epidemiological link. Three strains, two from these two patients and one from the chicken, were isolated. Genome sequencing and analyses of phylogenetic trees demonstrated that the two viruses were almost identical. We noted the presence of the PB2 E627K amino acid substitution that was not present in isolates from the first wave, as well as two new mutations in the NA gene and six in the PB2 gene. Drug sensitivity testing showed that the new isolates were resistant to oseltamivir but sensitive to peramivir. Conclusions The two patients from one family cluster were probable human-to-human transmission cases. The new isolates were sensitive to peramivir but showed reduced sensitivity to oseltamivir. [ABSTRACT FROM AUTHOR]

The deregulation of Bcl2L12 expression in cancer has been recognized, but the causative factors are unknown. Histone acetyltransferases (HAT) play critical roles in the regulation gene transcription. This study tests a hypothesis that the aberrant activities of HAT induce deregulation of Bcl2L12 in nasopharyngeal cancer (NPC). In this study, human NPC tissues were collected from the clinic. The expression of Bcl2L12 and HATs in NPC cells was analyzed by real time RT-PCR and Western blotting. NPC cell apoptosis was analyzed by flow cytometry. The results showed that by screening the subtypes of HAT, the levels of HAT1 were uniquely higher in NPC as compared with non-cancer nasopharyngeal tissue. The levels of Bcl2L12 in NPC cells were positively correlated with HAT1. HAT1 involved in the STAT5 binding to the Bcl2L12 promoter. HAT1 increased the expression of Bcl2L12. Bcl2L12 mediated the effects of HAT1 on suppressing NPC cell apoptosis. Absorption of the HAT1 shRNA plasmid-carrying liposomes induced NPC cell apoptosis. In conclusion, inhibition of HAT1 can induce NPC cell apoptosis via increasing Bcl2L12 expression, which can be a potential therapy for NPC treatment. [ABSTRACT FROM AUTHOR]

Background Appropriate antimicrobial dosing for patients receiving continuous venovenous hemofiltration (CVVH) is complex. Pharmacist participation in antimicrobial dosing adjustment for patients receiving CVVH may be advantageous. Methods A comparative study was performed in a China hospital intensive care unit (ICU).Patients receiving CVVH in the intervention group received antimicrobial dosing adjustment service by pharmacists from January 2012 to June 2012, whereas patients in the control group received routine medical care between July 2012 and December 2012. The primary outcomes including patients’ length of ICU stay, mortality in ICU, ICU hospitalization costs, and the occurrence of adverse drug events (ADEs) were then compared. Results 87 and 93 patients were included in the control and intervention groups. During the intervention period, pharmacists made 256 antimicrobial dosing adjustment recommendations for 93 enrolled patients receiving CVVH, of which 224 (87.5%) recommendations were accepted by physicians. Changing in CVVH-related variables (175, 68.4%) were the most common risk factors for dosing errors, whereas β-lactams (131, 51.2%) were the most frequency of antimicrobials associated with dosing errors. Compared with the control group, pharmacist dosing adjustment resulted in £1637.7 cost savings per patient, and 2.36 times reduction of antimicrobial-related adverse drug events (ADEs) (11 vs 26, P = 0.002), while length of ICU stay and mortality in ICU showed no significant difference ( P > 0.05). Conclusions The involvement of pharmacist to participate in the ICU team rounds for patients receiving CVVH is associated with cost savings and reduction of ADEs. Hospital may consider employing ICU pharmacists. [ABSTRACT FROM AUTHOR]

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV)., Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment., Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p =0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p =0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p =0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p =0.031)., Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Objective: To investigate whether the combination of neoadjuvant hyperthermic intraperitoneal chemotherapy (NHIPEC) plus intravenous neoadjuvant chemotherapy (IV NACT) has superior efficacy to IV NACT alone., Design: Retrospective cohort study., Setting: Two tertiary referral university hospitals., Population: Patients with ovarian cancer who received NACT-interval debulking surgery (IDS) between 2012 and 2020., Methods: The tumour response to NACT was evaluated with the chemotherapy response score (CRS) system. Survival outcomes were compared., Main Outcome Measures: CRS 3, progression-free survival (PFS), and overall survival (OS)., Results: In total, 127 patients were included, and 46 received NHIPEC plus IV NACT. The addition of NHIPEC was independently associated with an increased likelihood of CRS 3 (p = 0.033). Patients who received NHIPEC + IV NACT had significantly improved PFS compared with those who received IV NACT alone (median PFS: 22 versus 16 months, p < 0.001). The use of NHIPEC was identified as an independent predictor of PFS (p < 0.0001). OS did not differ significantly between treatment groups (p = 0.062), although a trend favouring NHIPEC was noted. Incidence of grade 3-4 adverse events and the surgical complexity score of IDS were similar between the two groups., Conclusions: Compared with IV NACT alone, the combination of NHIPEC and IV NACT resulted in improved tumour response and longer PFS. The addition of NHIPEC did not increase the risk of adverse effects or affect the complexity of IDS., (© 2022 John Wiley & Sons Ltd.)

Objective: To investigate whether CA125 normalization following neoadjuvant chemotherapy (NACT) can complement the chemotherapy response system (CRS) in the prognostication of patients with tubo-ovarian high-grade serous carcinoma (HGSC). Methods: In total, 118 HGSC patients who received NACT followed by interval debulking surgery (IDS) for FIGO stage IIIC-IV disease were included, and their clinical data were retrospectively reviewed. The primary endpoint was progression-free survival (PFS). Cox regression analysis was performed to identify predictors of PFS. Results: Following NACT, CRS3 was noted in 35 patients (29.7%), and CA125 normalization (≤ 35 U/ml) was noted in 54 patients (45.8%). Both CRS3 and CA125 normalization were identified as independent prognosticators of PFS. Combining these two factors, we stratified the 106 patients into three groups with different risks of recurrence: low-risk group (CRS3 + post-NACT CA125≤ 35 U/ml; n = 17, 14.4%), intermediate-risk group (CRS3 + post-NACT CA125 > 35 U/ml; n = 19, 16.1%) and high-risk group (CRS1-2; n= 82, 69.5%). The differences in PFS between the three groups were significant (log-rank test, P < 0.0001). In Cox regression analyses, the new stratification method was found to have an independent prognostic effect. Conclusion: Both the CRS system and the normalization of CA125 following NACT could reliably predict the risk of recurrence following primary treatment. The combination of the two factors refined the prognostic stratification of HGSC patients who were treated with NACT and IDS., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: In 2012, we proposed and described a modified triple incision technique (MTIT) for vulvar cancer patients with locally advanced disease. The MTIT has undergone a series of modifications, and a modified MTIT (M-MTIT) has been developed. The purpose of this study was to introduce the M-MTIT and compare it with the MTIT. Study design: This was a retrospective cohort study. Fifty-seven vulvar cancer patients with clinical stage T2 (≥ 4 cm) or T3 disease were included. Of these patients, 28 underwent the MTIT and 29 underwent the M-MTIT. Data on surgery-related complications and survival outcomes were compared. Results: Patients who were treated with the M-MTIT developed significantly less surgery-related morbidities than patients treated with the MTIT (24.1% vs. 60.7%, P = 0.005). Wound breakdown was the most common complication in our cohort, which occurred less frequently in the M-MTIT group than in the MTIT group (10.3% vs. 35.7%, P = 0.022). Multivariate logistic regression analysis identified the M-MTIT as an independent predictor of a reduced risk of wound breakdown. The incidence of other complications, including lymphedema, wound infection and cellulitis, was lower in the M-MTIT group than in the MTIT group; however, the differences did not reach statistical significance. The median follow-up time of this study was 33 months. Kaplan-Meier survival graphs did not show significant differences in recurrence-free survival or overall survival between the two groups. Conclusions: The M-MTIT correlates with lower morbidity rates than the MTIT and does not compromise oncological safety. The M-MTIT can be considered a safe and feasible option for vulvar cancer patients with locally advanced disease., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

A reliable disease model mimicking Enterovirus 71 (EV71) infection in humans is essential for understanding pathogenesis and for developing a safe and effective vaccine. Commonly used rodent models including mouse or rat models are not suitable for vaccine evaluation because the rodents are resistant to EV71 infection after they reach the age of 6 days. In this study, 21-day-old gerbils inoculated intraperitoneally (IP) with a non mouse-adapted EV71 strain developed neurological lesion-related signs including hind limb paralysis, slowness, ataxia and lethargy similar to those of central nervous system (CNS) infection of EV71 in humans. The infected gerbils eventually died of the neurological lesions and EV71 could be isolated from lung, liver, spleen, kidney, heart, spinal cord, brain cortex, brainstem and skeletal muscle. Significantly high virus replication was detected in spinal cord, brainstem and skeletal muscle by cellular analysis, real-time quantitative PCR (RT-PCR) and immunohistochemical staining. Histopathologic changes such as neuronal degeneration, neuronal loss and neuronophagia were observed in spinal cord, brain cortex, brainstem, and skeletal muscle along with necrotizing myositis and splenic atrophy. Gerbils that received two doses of inactive whole-virus vaccine showed no EV71-specific symptoms after challenged with EV71. In contrast, gerbils that received mock vaccination died of EV71-induced neuropathology after challenged with EV71. The result indicates that gerbils can serve as a reliable disease model for evaluating safety and efficacy of EV71 vaccine.

Objective: To analyse the emergence of YMDD motif (tyrosine-methionine-aspartate-aspartate) variants in patients with hepatitis B treated with lamivudine., Methods: The amino acid substitution from methionine or isoleucine at the YMDD motif at the HBV polymerase gene is a main mutation resistant to lamivudine treatment. Generated from a fragment of domain C of the polymerase gene, patients' HBV DNA, which had been positive previously became positive again ever since it had been negative during lamivudine therapy. Variants were detected by cleavage of the products of the three PCRs with following enzymes: FokI, SspI, Alw441. The results of PCR-RELP were analysed by 8.4% polypropylene acidemide gel electrophoresis. PCR-RFLP assay was compared to direct sequencing., Results: HBV DNA was positive again in 33 patients and positive for one year in 2 patients. YMDD variants were detected in serum 14 of 35 patients, YIDD variants in 4, YVDD variants in 6, and YI/MDD variants in 1; all were in concordance with the results of direct sequencing. The samples of other 3 patients showed YI/VDD mutations, as shown by direct sequencing. The results of PCR-RFLP assay of the mixed sera of YIDD and YVDD variants were similar to those sera of YI/VDD variants., Conclusion: PCR-RFLP is suitable for rapid detection of YMDD variants of viral polymerase in hepatitis B virus patients treated with lamivudine.