Pulmonary fibrosis(PF)is a chronic progressive lung disease caused by a variety of etiologies and is also a common outcome of various chronic inflammatory lung diseases.The incidence of pulmonary fibrosis is increasing year by year,with a high mortality rate that seriously threatens the life and health of patients.Although two drugs,pirfenidone and nintedanib,are already on the market for the treatment of pulmonary fibrosis,they can only slow down the progression of the disease but cannot reverse or stop the process of pulmonary fibrosis,and long-term use can produce a variety of adverse reactions.Therefore,it is highly necessary to develop new drugs for pulmonary fibrosis that are more targeted,effective,and well-tolerated by patients.The phosphatidylinositol-3-kinase(PI3K)signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis.Targeted inhibition of the PI3K signaling pathway may be an important direction for the development of new drugs for pulmonary fibrosis.At present,some PI3K signaling pathway inhibitors have shown good effects in preventing and treating pulmonary fibrosis,but most of them are still in the research stage.This article reviews the role of the PI3K signaling pathway in PF,further summarizes promising PI3K pathway inhibitors with PF therapeutic effects,including inhibitors in clinical trials and preclinical studies,and discusses their mechanisms of action and development prospects.

The neural circuit is the material carrier for the realization of brain function,consisting of a complex network of different neurons.Neural circuit identification technology tracks the structure and activity of specific neural circuits,to study their adequacy and necessity for brain function,which is crucial for understanding the pathogenesis of brain diseases.As a high-tech tool in the fields of neuroscience and brain science,neural circuit identification technology has been gradually introduced into basic traditional Chinese medicine(TCM)research in recent years.This systematic review considers the principles of neural circuit identification technology and progress in its application in the field of TCM neuroscience.We note that future developments in this field should be based on the overall concept of TCM characteristics and the design of syndrome differentiation and treatment.Further research on the neural circuit mechanisms of diverse method of TCM in diseases will help to promote the deep integration of TCM and modern neuroscience.

Objective:To explore the characteristics and factors affecting the occurrence of renal injury in patients with abnormal biochemical indexes of renal function after the use of immune checkpoint inhibitors (ICIs), and to provide reference for selection of clinical treatment regimen.Methods:Patients who were treated with immune checkpoint inhibitors researched and developed independently in China including camrelizumab, sintilimab, tislelizumab, and toripalimab from March 1, 2021 to February 28, 2022 and showed estimated glomerular filtration rate (eGFR) <90 ml/(min·1.73 m 2) and/or serum creatinine (Scr)>105 μmol/L were retrieved from the China Hospital Pharmacovigilance System. The clinical data including general information, anti-tumor treatment regimen, laboratory test results, and concomitant medications were collected. Patients were divided into kidney injury group and non-kidney injury group, and all the clinical characteristics were compared between the 2 groups, the influencing factors of kidney injury were analyzed using a binary logistic regression model, the odds ratio ( OR) and its 95% confidence interval ( CI) were calculated. Results:A total of 222 patients were entered in the analysis, including 170 males and 52 females, with a median age of 67 (36, 85) years. Of them, 144 patients were treated with carrilizumab, 38 with sindilizumab, 31 with tirelizumab, and 9 with treprolizumab; 29 patients (13.1%) developed kidney injury, including 26 cases of grade 1 and 3 cases of grade 2 renal injuries; the time of renal injury occurrence was 19-355 days after the first application of ICIs, and the median time was 108 days. After diagnosed of kidney injury, 13 out of 29 patients stopped ICIs, of which 6 had recovered kidney function and 7 had no improvement; 16 patients continued the ICIs treatment, of which 10 patients had recovered or improved kidney function and 6 had no improvement. The clinical characteristics of patients in the 2 groups were compared, and 10 variables including age, gender, baseline renal function, previous use of carboplatin, previous radiotherapy, combined chemotherapy containing cisplatin, combined paclitaxel chemotherapy, combined tyrosine kinase inhibitor (TKI) anti-vascular therapy, combined proton pump inhibitors, and combined radiotherapy were screened for the binary logistic regression analysis. The results showed that female ( OR=3.046, 95% CI: 1.149-8.077), ≤65 years ( OR=3.649, 95% CI: 1.435-9.274), combined TKI anti-vascular therapy ( OR=4.773, 95% CI: 1.496-15.227), and combined radiotherapy ( OR=8.655, 95% CI: 1.268-59.076) were independent risk factors for the development of kidney injury. Conclusions:The incidence of kidney injury in patients with eGFR <90 ml/(min·1.73 m 2) and/or Scr >105 μmol/L after using ICIs is 13.1%. In these patients, female, ≤65 years, combined TKI anti-vascular therapy, and combined radiotherapy may be risk factors for the development of ICI-associated kidney injury.

Objective:To explore the characteristics and factors affecting the occurrence of renal injury in patients with abnormal biochemical indexes of renal function after the use of immune checkpoint inhibitors (ICIs), and to provide reference for selection of clinical treatment regimen.Methods:Patients who were treated with immune checkpoint inhibitors researched and developed independently in China including camrelizumab, sintilimab, tislelizumab, and toripalimab from March 1, 2021 to February 28, 2022 and showed estimated glomerular filtration rate (eGFR) <90 ml/(min·1.73 m 2) and/or serum creatinine (Scr)>105 μmol/L were retrieved from the China Hospital Pharmacovigilance System. The clinical data including general information, anti-tumor treatment regimen, laboratory test results, and concomitant medications were collected. Patients were divided into kidney injury group and non-kidney injury group, and all the clinical characteristics were compared between the 2 groups, the influencing factors of kidney injury were analyzed using a binary logistic regression model, the odds ratio ( OR) and its 95% confidence interval ( CI) were calculated. Results:A total of 222 patients were entered in the analysis, including 170 males and 52 females, with a median age of 67 (36, 85) years. Of them, 144 patients were treated with carrilizumab, 38 with sindilizumab, 31 with tirelizumab, and 9 with treprolizumab; 29 patients (13.1%) developed kidney injury, including 26 cases of grade 1 and 3 cases of grade 2 renal injuries; the time of renal injury occurrence was 19-355 days after the first application of ICIs, and the median time was 108 days. After diagnosed of kidney injury, 13 out of 29 patients stopped ICIs, of which 6 had recovered kidney function and 7 had no improvement; 16 patients continued the ICIs treatment, of which 10 patients had recovered or improved kidney function and 6 had no improvement. The clinical characteristics of patients in the 2 groups were compared, and 10 variables including age, gender, baseline renal function, previous use of carboplatin, previous radiotherapy, combined chemotherapy containing cisplatin, combined paclitaxel chemotherapy, combined tyrosine kinase inhibitor (TKI) anti-vascular therapy, combined proton pump inhibitors, and combined radiotherapy were screened for the binary logistic regression analysis. The results showed that female ( OR=3.046, 95% CI: 1.149-8.077), ≤65 years ( OR=3.649, 95% CI: 1.435-9.274), combined TKI anti-vascular therapy ( OR=4.773, 95% CI: 1.496-15.227), and combined radiotherapy ( OR=8.655, 95% CI: 1.268-59.076) were independent risk factors for the development of kidney injury. Conclusions:The incidence of kidney injury in patients with eGFR <90 ml/(min·1.73 m 2) and/or Scr >105 μmol/L after using ICIs is 13.1%. In these patients, female, ≤65 years, combined TKI anti-vascular therapy, and combined radiotherapy may be risk factors for the development of ICI-associated kidney injury.

Objective:To explore CT and MRI features of the endolymphatic sac tumor (ELST).Methods:The CT and MRI morphology confirmed by surgical pathology for 19 patients with ELST were retrospectively analyzed from June 2011 to May 2019 in Eye & ENT Hospital of Fudan University. The features of CT and MRI included location, size, adjacent structures invasion, CT values, bone destruction, features of T 1WI and T 2WI, enhancement distribution characteristics, dynamic enhancement curve morphology, DWI signal characteristics. The ADC values of the lesions and ipsilateral medial pterygoid muscles were compared using a paired t test. Results:Nineteen ELST patients (one with bilateral diseases) were included. Totally 20 ears (right 9 and left 11) of 13 females and 6 males were studied. The masses with slightly high-density and obscure boundary were located around the vestibular aqueduct at the posterior edge of the petrosal bone. Bone destruction involved mastoid process of the middle ear (16 ears), jugular foramen (11 ears), semicircular canal (10 ears), facial nerve canal (7 ears) and internal auditory canal (9 ears). A large amount of residual bone could be found in the interior of nineteen masses. The CT value was (78.6±21.9) HU. The lesion showed central iso-intensity and peripheral hyperintensity on T 1WI and T 2WI in 16 ears, while no obvious hyperintensity on T 1WI in the other 4 ears. The hyperintensity on T 1WI was around the margin of the lesion in 10 ears, situated at lateral side in 5 ears and all over the lesion in 1 ear. Flow voids signals could be seen in 9 ears as well. Liquid-liquid plane was seen on T 2WI in 2 ears. The solid mass portion which showed iso-intensity on both T 1WI and T 2WI presented marked enhancement on contrast-enhanced T 1WI, while other part of the mass no enhancement. DWI of 14 ears illustrates no evidence of restricted diffusion, and the ADC value [(1.25±0.08)×10 -3 mm 2/s] was slightly higher than that of the medial pterygoid muscles ( t=4.437, P=0.001). The style of time-signal intensity curves of the dynamic contrast-enhanced MRI was rapidly ascending followed by descending curves in 2 ears. Conclusion:Imaging findings of ELST have some characteristics, including located around the vestibular aqueduct at the posterior edge of the petrosal bone, bone destruction, peripheral hyperintensity on T 1WI and no restricted diffusion, which is helpful for its diagnosis.

[ABSTRACT] SET domain-containing protein 2 (SETD 2), an epigenetic gene encoding a tri-methyltransferase of histone H3 lysine 36 (H3K36), has been found to be recurrently mutated in a variety of malignancies in the past few decades. SETD2 mutation was firstly identified in solid tumors including renal clear cell carcinoma, glioma and breast cancer, then recently found in multiple hematological malignancies. Increasing evidences have revealed that SETD2 played a pivotal role in regulating the functions of hematopoietic stem cells and the normal development of hematopoietic system. Inactivating mutations of SETD2 can promote the pathogenesis of myeloid, lymphoid leukemia and lymphoma as well as the development of therapeutic resistance. Further elucidation of the molecular mechanisms underlying SETD2-associated hematological malignancies and drug resistance is of great significance for the innovations of diagnosis and treatment methods. In this review, the progress of SETD2 in hematological malignancies are elaborated.

OBJECTIVE: To evaluate the application of decision tree method and Logistic regression in the prediction of acute myocardial infarction (AMI) events. METHODS: The clinical data of 295 patients, who underwent coronary angiography due to angina or chest pain with unidentified causes in Zhejiang provincial People's Hospital during October 2018 and April 2019, were retrospectively analyzed. Fifty five patients were identified as AMI. Logistic regression and decision tree methods were performed to establish predictive models for the occurrence of AMI, respectively; and the models created by decision tree analysis were divided into Logistic regression-independent model (Tree 1) and Logistic regression-dependent model (Tree 2). The performance of Logistic regression and decision tree models were compared using the area under the receiver operating characteristic (ROC) curve. RESULTS Logistic regression analysis showed that history of coronary artery disease, multi-vessel coronary artery disease, statin use and apolipoprotein (ApoA1) level were independent influencing factors of AMI events (all P<0.05). Logistic regression-independent decision tree model (Tree 1) showed that multi-vessel coronary artery disease was the root node, and history of coronary artery disease, ApoA1 level (the cutoff value:1.314 g/L) and anti-platelet drug use were descendant nodes. In Logistic regression-dependent decision tree model (Tree 2), multi-vessel coronary artery disease was still the root node, but only followed by two descendant nodes including history of coronary artery disease and ApoA1 level. The area under the curve (AUC) of ROC of Logistic regression model was 0.826, and AUCs of decision tree models were 0.765 and 0.726, respectively. AUC of Logistic regression model was significantly higher than that of Tree 2 (95% CI=0.041-0.145, Z=3.534, P<0.001), but was not higher than that of Tree 1 (95% CI=-0.014-0.121, Z=-1.173, P>0.05). CONCLUSIONS The predictive value for AMI event was comparable between Logistic regression-independent decision tree model and Logistic regression model, implying the data mining methods are feasible and effective in AMI prevention and control.