Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

Objective To investigate the clinical efficacy of CT-guided drilling,hematoma aspiration and drainage for senile cerebellar hemorrhage.Methods A retrospective analysis was performed on 89 very old patients(75-89 years old)with cerebellar hemorrhage admitted to our hospital from January 2016 to December 2022.According to their wishes,different surgical treatments were adopted,and thus they were divided into puncture group(42 cases,CT-guided drilling,aspi-ration and drainage for hematoma)and craniotomy group(47 cases,craniotomy).GCS,preopera-tive hematoma volume,length of ICU stay,postoperative complications,mortality rate and the mRS score in 3 months postoperatively in the survival were compared between the 2 groups.Re-sults There were no significant differences in age,male ratio,GCS score,preoperative hematoma volume,recurrence rate at 24 h postoperatively and mortality rate at 3 months postoperatively be-tween 2 groups(P＞0.05).The puncture group had significantly shorter length of ICU stay(7.10±1.43 dvs 8.87±1.39 d,P=0.000)and lower intracranial infection rate(4.76％vs 19.15％,P=0.040)than the craniotomy group.In 3 months of follow-up after surgery,the rate of good mRS score was higher in the puncture group than the craniotomy group,and the mRS score was lower in the former group than the latter one(P＜0.05).Conclusion CT-guided drilling,aspiration and drainage for hematoma can reduce the infection rate and improve the prognosis,and is an effective approach in the treatment of patients over 75 years old with cerebellar hemorrhage.

Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.

Objective To explore the efficacy of the retrosigmoid sinus approach through the cerebellopontine angle in the treatment of pontine hemorrhage.Methods A retrospective analysis was performed on 108 patients with pontine hemorrhage in Kaifeng Central Hospital from January 2016 to June 2022.They were divided into two groups according to the treatment methods,the conservative treatment group and the craniotomy treatment group(transcerebellopontine angle sigmoid sinus posterior approach).There were 94 cases in the conservative treatment group and 14 cases in the surgical treatment group.First analysis was conducted to examined whether there are differences in gender,age,Glasgow Coma Score(GCS)on admission,bleeding volume,comorbidities and complications between the two groups.Additional analysis was performed to analyze modified Rankin(modified Rankin scale,mRS)score and mortality rate after three month follow-up in case there was no significant difference at first analysis.Results There were no statistical differences in gender,age,Glasgow Coma Score(GCS)on admission,bleeding volume,comorbidities and complications between the two groups.After 3 months of follow-up,49 patients died in the conservative treatment group and 3 patients in the craniotomy treatment group.The mortality rates of the two groups were 52.1％and 21.4％respectively(χ2=4.600,P<0.05)).There was a statistical difference in the mortality rate between the two groups,and the mortality rate of the craniotomy treatment group was significantly lower than that of the conservative group.The modified Rankin score was 4(3,5)in the conservative treatment group and 3(2,3)in the craniotomy group(Z=-2.994,P<0.01).The modified Rankin score in the craniotomy group was lower than that in conservative treatment group after 3 months.Conclusion Microsurgery through the cerebellopontine angle retrosigmoid sinus approach to treat pontine hemorrhage can significantly reduce patient mortality and improve prognosis and is an effective surgical treatment method.

ObjectiveTo observe the effect of aqueous extract of Sophorae Tonkinensis Radix et Rhizoma （STRR） on rheumatoid arthritis （RA） and to explore the anti-bone destruction mechanism based on phosphatidylinositol 3-kinase （PI3K）/serine/threonine-protein kinase （Akt） pathway. MethodHigh-performance liquid chromatography （HPLC） was used to determine the content of main active components in aqueous extract of STRR， and type Ⅱ collagen to induce RA （CIA） in mice. The blank group， model group， methotrexate （MTX） group （0.5 mg·kg^-1）， and low-dose （100 mg·kg^-1） and high-dose （200 mg·kg^-1） STRR aqueous extract groups were designed. Joint swelling was observed and clinical scores of CIA mice were calculated. Pathological changes of mouse joints were observed based on hematoxylin and eosin （HE） staining， and Micro-CT was performed to monitor joint destruction. TRAP staining was used to observe osteoclast formation in mouse joint， and Western blot to detect the expression of key proteins in PI3K/Akt signaling pathway in mouse joint tissue. ResultThe model group demonstrated higher degree of joint swelling， clinical scores of CIA， and degrees of synovial hyperplasia， inflammatory cell infiltration （P<0.01）， and joint destruction， more osteoclasts， and higher levels of matrix metallopeptidase-9 （MMP-9）， cathepsin K （CTSK）， nuclear factor of activated T-cells cytoplasmic 1 （NFATc1）， PI3K， and phosphorylated-Akt （p-Akt） proteins than the blank group （P<0.01）. Compared with the model group， the low-dose and high-dose aqueous extract of STRR alleviated joint swelling， reduced the clinical scores of CIA mice （P<0.05， P<0.01）， relieved the pathological changes of joint tissue （P<0.01） and joint destruction， decreased osteoclasts （P<0.05， P<0.01）， and lowered the levels of PI3K/Akt signaling pathway-related proteins in joint tissue of mice （P<0.01）. ConclusionThe aqueous extract of STRR can significantly delay the inflammatory response of RA and especially inhibit bone destruction by down-regulating the PI3K/Akt signaling pathway.

Objective:To evaluate the independent prognostic value of minute ventilation/carbon dioxide production slope (VE/Vco 2 slope)on heart failure after acute myocardial infarction. Methods:131 patients with acute myocardial infarction (AMI) treated in the cardiology department of China-Japan Friendship Hospital from September 2018 to September 2019 were collected and followed up 3 months after discharge. They were divided into heart failure (HF) group and non-heart failure (NHF) group. All the patients underwent cardiopulmonary exercise test (CPET) before discharge.Results:Three months after discharge, the VE/Vco 2 slope was higher in HF group than in NHF group (36.7±3.8 vs 29.7±4.0, P=0.014). The best VE/Vco 2 slope cutoff for the prediction of heart failure after 3 month was 33.05 with a sensitivity of 81.4% and a specificity of 80.6% [area under curve (AUC) was 0.844, P<0.001]. VE /Vco 2 slope level was an independent predictor of heart failure in patients with acute myocardial infarction after discharge ( OR=1.245, 95% CI: 1.021-1.366, P=0.019). Other independent indicators related to heart failure included N-terminal pro-B type natriuretic peptid (NT-proBNP) level ( OR=1.283, 95% CI: 1.019-1.399, P=0.033). Conclusions:VE/Vco 2 slope yielded strong, independent predictive value for heart failure at 3 month after discharge to AMI patients.

Objective:To investigate the feasibility of ventral-combined-dorsal exposure of middle hepatic vein via caudal approach in laparoscopic anatomic hemihepatectomy of liver cancer.Methods:A retrospective analysis was performed on the clinical data of 44 patients undergoing laparoscopic antecedent hemihepatectomy with the ventral-combined-dorsal exposure of middle hepatic vein via caudal approach in the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) from January 2021 to September 2021. Among the 44 patients, there were 24 male and 20 female patients, aged 56-66 (61±5) years. The operative time, intraoperative blood loss, occlusion time of the first hilum hepatis, postoperative complications and postoperative hospital stay were analyzed.Results:All 44 patients underwent the surgery successfully. The average operation time was (259.3±33.4) min. Intraoperative blood loss was (113.8±31.0) ml, and no intraoperative blood transfusion was performed. The mean intraoperative occlusion time of the first hilum was (56.1±7.1) min. No postoperative hemorrhage and biliary fistula and other complications occurred. The mean postoperative hospital stay is (9.3±1.4) days. Pathological examination confirmed hepatocellular carcinoma in 36 cases and intrahepatic cholangiocarcinoma in 8 cases.Conclusion:The ventral-combined-dorsal exposure of middle hepatic vein via caudal approach benefits exposure of middle hepatic vein in laparoscopic anatomic hemihepatectomy, reducing intraoperative accidental bleeding and ensuring surgical safety.

Objective:To evaluate surgical therapy for patients of hepatocellular carcinoma(HCC) with bile duct tumor thrombi(BDTT).Methods:A retrospective analysis was made on 66 patients with HCC and BDTT undergoing surgical treatment at the First Affiliated Hospital of Hunan Normal University from Jan 2011 to Dec 2016.Results:The overall median survival time of the patients was 31 months. The 1, 3, and 5-year survival rates were 87.9%, 45.5%, and 13.6%, respectively. Univariate analysis showed hepatitis B virus, liver cirrhosis and history of drinking, AFP≥200 ng/ml, tumor resection combined with biliary incision to remove tumor thrombus, tumor undifferentiated/poorly differentiated, tumor diameter ≥50 mm, AJCC 8th stage Ⅲ/Ⅳ and number of lesions ≥ 2 were risk factors for postoperative survival (all P<0.05). Multivariate analysis showed that drinking history, undifferentiated/poorly differentiated tumor, tumor diameter ≥50 mm, and AJCC 8th Ⅲ/Ⅳ stage were independent risk factors (all P<0.05). Conclusion:Surgical resection of HCC combined with BDTT can achieve a satisfactory survival and prognosis.

Objective: To evaluate whether the self-designed single-channel intracavitary applicator yields equivalent clinical efficacy and safety to the standard Fletcher-type three-channel applicator in the high-dose-rate (HDR) brachytherapy for uterine cervical cancer. Methods: From December 2011 to April 2017, patients initially diagnosed with cervical cancer were randomly assigned into the external beam radiotherapy (EBRT)+ single-channel intracavitary applicator group (the patent single-channel group) and EBRT+ the Fletcher applicator group. Whole pelvis irradiation was delivered with 6-MV photons via a four-field box variant or anterior and posterior parallel fields. Five to six fractions of intracavitary brachytherapy were performed at a dose of 7 Gy at point A once a week after 30 Gy (BED at point A: 80-90 Gy). Chemotherapy was given with intravenous injection of cisplatin at a dose of 40 mg/m² once weekly during EBRT.Clinical efficacy and safety were evaluated after the treatment. Results: In total, 150 eligible cases were assigned into the Fletcher applicator group and 149 cases into the patent single-channel group. The short-term clinical efficacy and acute toxicity did not significantly differ between two groups. The response rate was 94.0% in the Fletcher group, and 94.7% in the patent single-channel group. In the Fletcher applicator group, 76(50.7%) patients developed ≥ grade 3 hematologic toxicity and 61(40.9%) in the patent group (P=0.195). Conclusions: The self-designed patent single-channel intracavitary applicator yields equivalent clinical efficacy and safety (acute toxicity) to the standard Fletcher-type three-channel applicator in the HDR brachytherapy for uterine cervical cancer. Clincal Trial Registration Chinese Clinical Trial Registry (ChiCTR-TRC-12002321).

Butanol is not only an important chemical feedstock but also expected to become a new generation biofuel. Thus, biological butanol production using renewable feedstocks has attracted renewed attention due to the worries of global oil supply and its impact on social and economic development. However, compared with petrochemical-derived butanol, biological butanol production is still not economically competition, because of its major drawbacks: high cost of the feedstocks, low butanol concentration in the fermentation broth and the co-production of low-value byproducts acetone and ethanol. Recently, Shanghai cooperative bio-butanol group (SCBG) developed a simple-to-complex technical route to improve bio-butanol production with a focus on: increasing butanol ratio in the solvent through metabolic engineering of Clostridia spp.; introducing and optimizing the butanol synthetic pathway in the species with high butanol tolerance; overcoming the glucose repression effect to utilize low-cost non-grain based feedstocks. SCBG believes that, through extensive domestic and international industry-university-research cooperation, a sustainable and economically viable process for biological butanol production can be established in the near future.
Biofuels ; Butanols ; metabolism ; Clostridium ; genetics ; metabolism ; Clostridium beijerinckii ; genetics ; metabolism ; Fermentation ; Genetic Engineering ; methods ; Industrial Microbiology ; methods ; trends