Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

A 82-year-old man was admitted to hospital with fever,unresponsiveness,elevated hypersensitive C-reactive protein and neutrophile granulocyte.Ceftriaxone was administrated by intravenous dripping in the emergency room,but the effect was not satisfactory.Following his admission to the ward,cefoperazone sulbactam were given.Elizabethkingia meningoseptica was identified by blood culture and further confirmed by 16S rRNA sequencing.The lumbar puncture showed that cerebrospinal fluid pressure was 80 mmH2O(1 mmH2O=0.0098 kPa)and biochemical results were normal.After 11 days of cefoperazone sulbactam treatment,the patient was discharged with negative blood culture.The hypersensitive C-reactive protein and neutrophile granulocyte had also declined.The patient received levofloxacin tablets for anti-infection treatment for 14 d after discharge.No signs of infection were observed in three months'following up.

Objective:To construct a nomogram model for predicting the risk of leukopenia among tuberculosis patients receiving anti-tuberculosis therapy.Methods:A total of 2 681 tuberculosis patients admitted to the affiliated Dongyang Hospital of Wenzhou Medical University from Jan 2013 to Jun 2024，were enrolled in this study. All cases received first line anti-tuberculosis treatment and were randomly divided into training（ n=1 876）and validation groups（ n=805）at a ratio of 7∶3. The endpoint was the occurrence of leukopenia during anti-tuberculosis therapy. In the training group，the predictors were screened by Lasso regression and multivariable Logistic regression analysis，and used to establish a nomogram prediction model. The discrimination power，fitness and clinical applicability were evaluated using the receiver operating characteristic（ROC）curve，calibration curve and decision curve analysis，respectively. Several machine learning models based on different methods（random forest，support vector machine，extreme gradient boosting and naive Bayes）were also constructed in the validation group. Results:There were 15.0%（273/1 876）and 15.9%（128/805）of cases developing leukopenia during anti-tuberculosis therapy in the training group and validation groups，respectively. Following Lasso regression analysis，the multivariable Logistic regression analysis showed that age ≥65 years（ OR=2.997，95% CI 2.185-4.128），alcohol consumption（ OR=4.803，95% CI 3.502-6.593）and diabetes（ OR= 5.459，95% CI 3.914-7.621）were risk factors related to the occurrence of leukopenia；while the higher levels of baseline hemoglobin（ OR=0.979，95% CI 0.971-0.987）and platelet count（ OR=0.996，95% CI 0.995-0.998）were protective factors. Based on these five factors，a nomogram prediction model was developed. The areas under ROC curve（AUCs）were 0.836（95% CI 0.810-0.863）and 0.818（95% CI 0.776-0.860）in the training group and the validation group，respectively. Moreover，this model had good fitness and clinical applicability. The discrimination power of nomogram model was comparable to those of machine learning models. Conclusion:The established nomogram model in this study has good discrimination power，calibration ability and clinical applicability for predicting the risk of leucopenia in tuberculosis patients undergoing anti-tuberculosis therapy.

Objective:To construct a nomogram model for predicting the risk of leukopenia among tuberculosis patients receiving anti-tuberculosis therapy.Methods:A total of 2 681 tuberculosis patients admitted to the affiliated Dongyang Hospital of Wenzhou Medical University from Jan 2013 to Jun 2024，were enrolled in this study. All cases received first line anti-tuberculosis treatment and were randomly divided into training（ n=1 876）and validation groups（ n=805）at a ratio of 7∶3. The endpoint was the occurrence of leukopenia during anti-tuberculosis therapy. In the training group，the predictors were screened by Lasso regression and multivariable Logistic regression analysis，and used to establish a nomogram prediction model. The discrimination power，fitness and clinical applicability were evaluated using the receiver operating characteristic（ROC）curve，calibration curve and decision curve analysis，respectively. Several machine learning models based on different methods（random forest，support vector machine，extreme gradient boosting and naive Bayes）were also constructed in the validation group. Results:There were 15.0%（273/1 876）and 15.9%（128/805）of cases developing leukopenia during anti-tuberculosis therapy in the training group and validation groups，respectively. Following Lasso regression analysis，the multivariable Logistic regression analysis showed that age ≥65 years（ OR=2.997，95% CI 2.185-4.128），alcohol consumption（ OR=4.803，95% CI 3.502-6.593）and diabetes（ OR= 5.459，95% CI 3.914-7.621）were risk factors related to the occurrence of leukopenia；while the higher levels of baseline hemoglobin（ OR=0.979，95% CI 0.971-0.987）and platelet count（ OR=0.996，95% CI 0.995-0.998）were protective factors. Based on these five factors，a nomogram prediction model was developed. The areas under ROC curve（AUCs）were 0.836（95% CI 0.810-0.863）and 0.818（95% CI 0.776-0.860）in the training group and the validation group，respectively. Moreover，this model had good fitness and clinical applicability. The discrimination power of nomogram model was comparable to those of machine learning models. Conclusion:The established nomogram model in this study has good discrimination power，calibration ability and clinical applicability for predicting the risk of leucopenia in tuberculosis patients undergoing anti-tuberculosis therapy.

A 82-year-old man was admitted to hospital with fever, unresponsiveness and elevated hypersensitive C-reactive protein, neutrophile granulocyte. Ceftriaxone was administrated by intravenous dripping in the emergency room, but the effect is not satisfied. Following his admission to the ward, anti-infection treatment started and antibiotics including cefoperazone sulbactam were given. Elizabethkingia meningoseptica was identified by blood culture and 16S rRNA sequencing. The lumbar puncture showed that cerebrospinal fluid pressure was 80 mmH₂O (1 mmH₂O=0.0098 kPa), and biochemical results were normal. After 11 days of anti-infection treatment, the patient was discharged with negative blood culture,and his hypersensitive C-reactive protein and neutrophile granulocyte declined. The patient received levofloxacin tablets for anti-infection treatment for 14 d after discharge, and no signs of infection were observed in three months' following up.

Objective:To explore the clinical effects of artificial dermis combined with split-thickness skin for repairing wounds with bone and tendon exposure in hands and feet.Methods:A prospective randomized controlled study was conducted. From October 2018 to February 2020, 82 patients with bone and tendon exposed wounds in hands and feet admitted to the Department of Burns of Zhengzhou First People′s Hospital who met the inclusion criteria were selected. All the patients were divided into flap group (41 cases, including 27 males and 14 females) and artificial dermis+split-thickness skin group (41 cases, including 29 males and 12 females) according to the random number table, with age of (37±7) years. After complete debridement of wounds of patients in the two groups, the wounds of patients in flap group were transplanted with anterolateral femoral free flaps; the wounds of patients in artificial dermis+split-thickness skin group were grafted with artificial dermis with continuous negative pressure suction applied, and then grafted with split-thickness skin from autologous lateral thigh once the vascularization of artificial dermis was completed. One week after autologous skin graft/flap grafting, the survival of wound graft was observed and the graft survival rate was calculated. The complete wound healing time, number of operation, length of hospital stay, hospitalization cost, and the occurrence of surgery-related complications during hospitalization after autologous skin graft/flap grafting were recorded, and the incidence of complications was calculated. Six months after autologous skin graft/flap grafting, the scar hyperplasia of recipient area was evaluated by Vancouver Scar Scale (VSS), while the recovery of hand and foot function was evaluated by Total Action Mobility (TAM) System Rating method and American Orthopaedic Foot and Ankle Society Ankle and Hindfoot Function Scale (AOFAS-AHS), respectively. Data were statistically analyzed with chi-square test, Fisher's exact probability test, and independent sample t test. Results:One week after autologous skin graft/flap grafting, the survival rates of wound grafts were similar in the two groups ( P>0.05). The complete wound healing time and length of hospital stay were (29±5) and (35±5) d for patients in artificial dermis+split-thickness skin group, respectively, which were significantly longer than (22±4) and (28±5) d in flap group ( t=6.96, 6.22, P<0.01). Compared with those in flap group, the number of operations was fewer ( t=7.39, P<0.01), the incidence of surgery-related complications during hospitalization after autologous skin graft/flap grafting was lower ( P<0.01), but there was no significant change in hospitalization cost of patients in artificial dermis+split-thickness skin group ( P>0.05). Six months after autologous skin graft/flap grafting, the VSS scores of recipient area of patients in the two groups were similar ( t=0.32, P>0.05); the TAM score of hand function and AOFAS-AHS score of foot function of patients in artificial dermis+split-thickness skin group were 40±6 and 62±12, respectively, which were significantly higher than 34±6 and 53±11 of flap group ( t=4.66, 3.41, P<0.01). Conclusions:The combined application of artificial dermis and split-thickness skin results in fewer number of operation compared with using flaps in the repair of wounds with bone and tendon exposure in hands and feet, reducing the incidence of surgery-related complications and improving the postoperative hand and foot joint function of patients, without significant scar hyperplasia, although it may also prolong the wound healing time and length of hospital stay accordingly.

Bombyx mori is a lepidopteran insect with important economic value. Bombyx mori nucleopolyhedrovirus (BmNPV) causes huge economic loss to silkworm industry in China every year. The objective of this study is to determine the anti-BmNPV mechanism of Bombyx mori strain NC99R, and to provide a basis for understanding the molecular mechanism of the silkworm resistance strain. The normal control Dazao (DZ) strain and the NC99R resistant strain were fed with occlusion bodies (OB). The median lethal dose (LD50) analysis of the DZ and NC99R showed that the LD50 of DZ was 1.2×10⁵ OBs/larva, while NC99R was 1.8×10⁶ OBs/larva. The LD50 of the NC99R was about 15 times higher than the DZ. The mortality of DZ and NC99R were analyzed, which were fed with 1×10⁶ OBs/larva and injection with 1×10⁶ BVs/larva. The results showed that the death peak of DZ was concentrated in the 4th to 6th day. And the death peak of NC99R was concentrated in the 6th to 8th day, with a delay of 1-2 days compared with the control. The BmNPV DNA copy number showed that the BmNPV genome in DZ proliferated rapidly. The copy number of BmNPV DNA in NC99R were increased slowly after oral infection and body injection. HE staining showed that midgut tissue has no significant difference between DZ and NC99R in the early stage of oral infection. At 96 h p.i., the nucleus of DZ midgut became larger and shedding. The NC99R had enlarged nuclei, but the cells were still arranged neatly. Finally, the expression of virus genes in different periods were analyzed by RT-PCR. The results indicated that the immediate early gene ie-1 expression levels began to down-regulate after 24 h p.i.. The early, late, and extremely late genes were also down-regulated, and finally maintained at a lower expression level.

Objective: To investigate the risk factors of postoperative acute kidney injury (AKI) in patients aged between 40 and 50 years old undergoing cardiac valvular surgery and the impact on outcome. Methods: The clinical data of 286 patients aged between 40 and 50 years old undergoing cardiac valve surgery in Guangdong Provincial People′s Hospital from January 2012 to December 2016 were analyzed retrospectively. Preoperative coronary angiography was performed in all patients. All patients enrolled were divided into AKI group and non-AKI group according to the existence or not of postoperative AKI. Patients with AKI were further divided into AKI stage 1, stage 2, and stage 3 groups according to KDIGO guideline. Demographic characteristics, preoperative clinical data including serum creatinine, estimated glomerular filtration rate, hemoglobin, uric acid, urinary protein, presence or absence of chronic kidney disease, left ventricular ejection fraction, pulmonary artery pressure, New York Heart Association (NYHA) functional classification, preoperative co-morbidity (hypertension, diabetes, anemia, cerebrovascular disease, peripheral artery disease), preoperative medication(vasoactive drugs, diuretic, renin-angiotensin system inhibitor (RASI), surgical data (contrast dosage in coronary angiography, type of cardiac valve surgery) were recorded and analyzed in this retrospective study. The risk factors for postoperative AKI and its impact on clinical outcomes (mortality, hospitalization expenses and Intensive Care Unit stay duration) were evaluated. Logistic regression analysis was used to determine the risk factors for postoperative AKI and the adjusted variables with P<0.2 were selected for the multivariate logistic regression analysis to define the independent determinants for AKI. Results: AKI was defined in 106 out of 286 enrolled patients, including 96 patients with AKI stage 1, 10 patients with AKI stage 2 and no patients with AKI stage 3. The proportion of coexisting cerebrovascular diseases was higher in AKI group than in non-AKI group (9(8.49%) and 5(2.78%), χ²=4.677, P=0.031), while there was no difference among other baseline data between the two groups. Multivariate logistic regression analysis showed that preoperative complications of cerebral vascular disease was an independent risk factor of postoperative AKI (OR=3.578, 95%CI 1.139-11.242, P=0.029). Five out of 106 AKI patients died during hospitalization while there was only 1 patient died among 180 patients without AKI. Patients with AKI after cardiac valve operation experienced higher mortality than patients without AKI (χ²=5.625, P=0.028). Further analysis showed that there was no difference in hospitalization mortality between patients with AKI stage 2 and stage (χ²=0.686, P=0.408) while the hospitalization mortality in patients with AKI stage 2 was higher than those without AKI (χ²=8.113, P=0.004). The hospitalization expenses in patients with AKI were 10.38(8.59,12.54) ×10⁴ RMB, significantly higher than that in patients without AKI (9.72(8.03,11.93) ×10⁴ RMB)(P=0.043). There was no difference in hospitalization expenses between patients with AKI stage 1 and without AKI (P=0.635). The hospitalization expenses in patients with AKI stage 2 was higher than those without AKI (P=0.023). Intensive Care Unit stay duration in patients with AKI was 3(1,4) days, significantly higher than those without AKI (P=0.044). There was no difference in Intensive Care Unit stay duration in patients with AKI stage 1 and without AKI (P=0.978), while Intensive Care Unit stay duration in patients with AKI stage 2 was significantly longer than those without AKI (P=0.006). Conclusions Preoperative complications of cerebral vascular disease is an independent risk factor of postoperative AKI. Non-senile patients with AKI after cardiac valvular surgery is associated with a higher proportion of mortality, hospitalization expenses and Intensive Care Unit stay duration as compared patients without postoperative AKI.

Objective To evaluate the value of proteinuria in predicting acute kidney injury (AKI) after cardiac surgery in elderly patients.Methods To retrospectively analyze the perioperative clinical data of elderly patients (age 60 or older)undergone cardiac surgery with cardiopulmonary bypass at Guangdong General Hospital from January 2005 to December 2010.Target patients were divided into two groups according to AKI defined by the KDIGO criteria.Data for those two groups were examined by single-factor analysis,and then logistic regression analysis was used to further determine independent factors of AKI after cardiac surgery.Results Among 848 elderly patients,AKI occurred in 524(61.8％) participants,including 39.2％(n=332)at AKI stage 1,16.6％ (n =141) at AK I stage 2,and 6.0 ％ (n=51) at AKI stage 3.A total of 15.9 ％ of patients(n=135) had preoperative proteinuria,including 12.4 ％ (n =106) with mild proteinuria,and 3.5 ％ (n =30) with heavy proteinuria.Logistic regression analysis showed that proteinuria was correlated with postoperative AKI.With the increase of proteinuria,the risk of AKI also increased,and the OR values of mild and severe proteinuria were 1.758 (1.020-3.029) and 4.758 (1.326-17.077),respectively.Conclusions Preoperative proteinuria may predict the occurrence of AKI after cardiac surgery in elderly patients.There is a gradual increase in the risk of AKI as proteinuria becomes more severe.Early institution of therapeutic interventions may be used in elderly patients with preoperative proteinuria undergoing cardiac surgery to attenuate the risk of AKI.

Objective Pulmonary hypertension (PH) was an independent predictor of mortality and new onset cardiovascular events in maintenance hemodialysis (MHD) patients. Recent studies revealed PH complicated by pericardial effusion (PE) increased mortality in non-CKD (chronic kidney disease) population. No such evidence existed in MHD patients. Methods We enrolled 108 MHD patients with diagnosed PH by echocardiography (61 with PE) between 2009 and 2011. All patients had been followed-up for 2 years. The endpoints were all-cause mor-tality, cardiovascular (CV) mortality and new onset CV events. Results The mean age was (60.2 ± 14.1) years, 55.6% were males and SPAP was (53.0 ± 15.4) mmHg. 12.0% were severe PH and 1.9% were moderate-to-severe PE. The overall mortality, cardiovascular mortality and new on-set cardiovascular events in PE and non-PE group were 34.4% vs. 21.3%、 23.0% vs. 12.8% and 54.1% vs. 42.6%, respectively (P > 0.05). Kaplan-Meier curve showed there was no difference on all-cause mortality , CV mortality nor new-onset CV events between PE and non-PE group (Log Rank P > 0.05). Conclusions Compared with patients without PE, the presence of PE in patients with PH did not increase the mortality and worsen the cardiovascular outcome in MHD patients.