Research progress in pharmacokinetics and therapeutic drug monitoring of tyrosine kinase inhibitors in the treatment of gastrointestinal stromal tumors / 中国药房

Tyrosine kinase inhibitors （TKIs） represent a class of small-molecule targeted drugs that improve the survival time of patients with gastrointestinal stromal tumor （GIST）. Imatinib， sunitinib， regorafenib， ripretinib， and avapritinib are commonly used TKIs in the clinical treatment of various types of GIST. This article provides a comprehensive review of the pharmacokinetics and therapeutic drug monitoring （TDM） of these five drugs， finding that there is significant individual variability in the pharmacokinetics of these drugs. Among them， the absorption of imatinib， regorafenib， and avapritinib are influenced by food intake. Imatinib should be taken with meals and 200 mL of water， regorafenib is taken with a low-fat meal， while avapritinib is taken on an empty stomach. TKIs are mainly metabolized by cytochrome P450 3A4 （CYP3A4）， and when used in combination with CYP3A4 inducers or inhibitors， drug exposure levels will significantly change； apart from metabolic enzymes， the exposure levels of TKIs are also influenced by interactions with the transporter proteins P-glycoprotein and breast cancer resistance protein. Currently， research on TDM for TKIs is still in the exploratory stage， with a substantial amount of literature reporting the effective concentrations of imatinib， sunitinib and regorafenib. However， the precise relationship between exposure levels and efficacy/ toxicity needs further exploration. Currently， there is a lack of research on the correlation between exposure levels and efficacy/ toxicity of ripretinib and avapritinib. It is recommended to implement TDM in patients taking these drugs and explore their therapeutic window in combination with pharmacokinetic models. The commonly used methods for clinical TDM of TKIs include immunoassay， chromatography， and surface-enhanced Raman spectroscopy， providing a technical basis for clarifying the therapeutic window of TKIs.

Inhibitory effect and mechanism of total flavonoids from Melicope pteleifolia on transplanted tumor of colorectal cancer in nude mice / 中国药房

OBJECTIVE To study the inhibitory effect and mechanism of total flavonoids from Melicope pteleifolia （TF-MPL） on transplanted tumor of colorectal cancer in nude mice. METHODS The transplanted tumor model of colorectal cancer was induced by injecting 0.2 mL colorectal cancer cell LoVo subcutaneously via the right armpit of nude mice. After successful modeling， nude mice were randomly divided into model group， 5-fluorouracil group （positive control， 10 mg/kg）， TF-MPL high- dose and low-dose groups （25， 12.5 mg/kg）； a normal group （normal saline containing 0.3% carboxymethyl cellulose sodium） without modeling was additionally set up， with 6 mice in each group. Each group was intraperitoneally injected with the corresponding drug solution/solvent for 21 consecutive days. The inhibitory rate of the transplanted tumor， liver and spleen index， and the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum were detected after the last medication； the morphological changes of tumor tissue were observed； immunohistochemical staining was used to detect protein expressions of Toll- like receptor 4 （TLR4） and nuclear factor-κB subunit p65 （NF-κB p65） in tumor tissue of nude mice. Western blot assay was used to detect protein expressions of TLR4， myeloid differentiation factor 88 （MyD88）， TNF receptor-associated factor 6 （TRAF6）， interleukin-1 receptor-associated kinase 1 （IRAK-1）， NF-κB p65 and caspase-3 in tumor tissue of nude mice. RESULTS Compared with the model group， TF-MPL high-dose group showed a significant decrease in tumor weight （inhibitory rate of 36.91%）， liver and spleen index， serum levels of TNF-α and IL-6 and protein expressions of TLR4， MyD88， TRAF6，IRAK-1 and NF- κB p65 （P＜0.05 or P＜0.01）； the expression of caspase-3 protein was increased significantly （P＜0.05）， and more tumor cell shrinkage and deformation， nuclear pyknosis and fragmentation were observed. CONCLUSIONS TF-MPL can significantly inhibit the growth of transplanted tumor of colorectal cancer in nude mice， the mechanism of which may be associated with reducing inflammatory response， inhibiting TLR4/MyD88/NF-κB signaling pathway， and promoting apoptosis in colorectal cancer cells.

Current status of AIDS knowledge, attitudes, practices and associated factors of high risk sexual behavior among college students in Tianjin City / 中国学校卫生

Objective@#To understand the current status of acquired immunodeficiency syndrome (AIDS) knowledge, attitudes, and practices of college students in Tianjin City and to further investigate the associated factors of high risk sexual behaviors, so as to provide a scientific and theoretical basis for accurate prevention and treatment of AIDS.@*Methods@#A stratified cluster random sample of 64 697 students in 56 colleges and universities in Tianjin City in November to December 2022 was investigated about the current status of AIDS knowledge, attitudes and practices. Information was collected using online survey via Questionnaire Star. Descriptive analysis was used for the current status of AIDS knowledge, attitudes and practices among college students. Chi square test and multiple Logistic regression analysis were used to analyze the influencing factors of high risk sexual behavior among college students.@*Results@#The AIDS awareness rate of college students in Tianjin City reached 87.33%. The sexual openness rate was 70.73 %. Among the 3 463 students who had sex during the past year, 42.13% of students reported high risk sexual behavior. Multivariate Logistic regression showed that female, having a romantic partner, having received sex education and prevention and treatment knowledge of AIDS were negatively associated with high risk sexual behavior ( OR =0.66, 0.59, 0.81, 0.59, P <0.05). Being in sophomore year, non heterosexuality (homosexuality, bisexuality, not knowing), prejudice against AIDS, and misunderstanding the testing methods for AIDS showed positive correlations with highrisk sexual behavior ( OR =1.22, 2.49, 2.30, 3.17, 1.43, 1.22 , P <0.05).@*Conclusions@#The awareness rate of AIDS in college students in Tianjin is high, but high risk sexual behaviors are still at a high level. Further targeted knowledge education and behavioral interventions are needed to scientifically prevent the spread of AIDS.

Mitochondria-specific near-infrared photoactivation of peroxynitrite upconversion luminescent nanogenerator for precision cancer gas therapy

Gas therapy is emerging as a highly promising therapeutic strategy for cancer treatment. However, there are limitations, including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision, associated with gas therapy. In this study, we developed a series of photoactivatable nitric oxide (NO) donors NRh-R-NO (R = Me, Et, Bn, iPr, and Ph) based on an N-nitrosated upconversion luminescent rhodamine scaffold. Under the irradiation of 808 nm light, only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence (FUCL) signal at 740 nm, ascribed to lower N-N bond dissociation energy. We also investigated the involved multistage near-infrared-controlled cascade release of gas therapy, including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation, the superoxide anion O2⋅- produced by the photodynamic therapy (PDT) effect of NRh-Ph, and highly toxic peroxynitrite anion (ONOO‒) generated from the co-existence of NO and O2⋅-. After mild nano-modification, the nanogenerator (NRh-Ph-NO NPs) empowered with superior biocompatibility could target mitochondria. Under an 808 nm laser irradiation, NRh-Ph-NO NPs could induce NO/ROS to generate RNS, causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation, which further induced tumor immunogenic cell death (ICD). In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy, demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL imaging. Collectively, this versatile strategy defines the targeted RNS-mediated cancer therapy.

Preliminary identification of the cloning， expression， and function of Marmota himalayana type I interferon receptor β subunit / 临床肝胆病杂志

ObjectiveTo clone the gene of Marmota himalayana type ‍Ⅰ interferon receptor β subunit （mhIFNAR2）， and to perform antibody preparation and functional identification. MethodsRT-PCR was used for amplification in the spleen tissue of Marmota himalayana to obtain the sequence， which was cloned to the prokaryotic expression vector pRSET-B to express the recombinant protein. Electrophoresis and Western blot were used for identification. BALB/c mice were immunized with the recombinant protein to prepare the polyclonal antibody of its extracellular domain； immunohistochemistry， immunofluorescence assay， and Western Blot were used for identification， and the method of siRNA blockade was used to investigate its function. An analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for comparison between two groups. ResultsA fragment of mhIFNAR2 （149‍ ‍—‍ ‍1 ‍300 bp） was obtained from spleen tissue， which showed the highest homology of 98.05% in marmot. A prokaryotic expression plasmid was successfully constructed for expression of the extracellular domain of the mhIFNAR2（50-181aa） and was named pRSET-B.mhIFNAR2， and the recombinant protein expressed by this plasmid had a molecular weight of 27 kD， a purity of about 95% after purification， and a concentration of 160 μg/mL. After BALB/c mice were immunized with the purified recombinant protein， 1∶1 000 specific polyclonal antibodies were obtained， and immunohistochemistry and immunofluorescence assay showed the expression in cell membrane and cytoplasm. Among the three siRNAs synthesized， the siRNA starting from the 277 locus （siRNA277） could silence the expression of target genes and weaken the interferon signaling pathway compared with the blank control group and the negative control group （both P<0.05）. ConclusionThe fragment of mhIFNAR2 is obtained， and the polyclonal antibody for the extracellular domain of mhIFNAR2 is successfully prepared， with relatively high titer and specificity， and can be used for immunohistochemistry， immunofluorescence assay， and Western blot.

The Prevention and Treatment of Pulmonary Nodules “Nodule-cancer Transformation” Based on the View of “Disease with Latent Pathogen Induced by a New Pathogen” / 中医杂志

As one of the pathogenic mechanisms contained in The Inner Canon of Yellow Emperor （《黄帝内经》）， “disease with latent pathogen induced by a new pathogen” means that the induced new pathogen resulted to a combination of the latent previous pathogen and the new pathogen， which caused the disease. Based on this， it is believed that the change of “nodule-cancer transformation” of pulmonary nodules is actually based on the deficiency of original qi， and the new pathogen induces the latent pathogens like phlegm coagulation， qi stagnation， blood stasis， toxicity， so healthy qi can not drive the pathogens out， and the long-time detention generated into cancerous turbidity， and deve-loped into cancerous tumour at the end. Therefore， based on the three-stage treatment of unformed cancer， dense cancerous toxin， and developed cancer， the clinical practice applied six methods of clearing， expelling， dissipating， tonifying， harmonizing， and transforming， taking into account both the manifestation and root cause， moving the treatment window of pulmonary nodules forward， attacking the pathogens when the toxin was not yet overbearing， supporting the healthy qi before declining， delaying the process of nodules-cancer transformation， and providing ideas for the prevention and treatment of pulmonary nodules “nodule-cancer transformation” in traditional Chinese medicine.

Research progress in the diagnosis and treatment of neurotrophic keratitis / 国际眼科杂志(Guoji Yanke Zazhi)

Neurotrophic keratitis(NK)is a degenerative corneal disease caused by impairment of trigeminal innervations. It can lead to spontaneous corneal epithelial defects, corneal ulceration and perforation. Early diagnosis of NK is crucial and requires accurate investigation of clinical history and thorough examination of ocular surface to determine clinical stage. Treatment for NK needs to be divided into stages according to disease severity. In addition to conventional treatments including artificial tears, blepharorrhaphy, and amniotic membrane transplantation, there are also emerging treatments such as targeted drug therapy and corneal neurotization. This article summarized the epidemiology, clinical manifestations and classification, etiology, diagnosis, differential diagnosis and treatment of NK, aiming to provide reference for the early diagnosis and treatment of NK in the future.

Treatment of Inflammatory Bowel Disease by Targeting M1/M2 Macrophage Polarization Balance with Traditional Chinese Medicine and Active Components： A Review / 中国实验方剂学杂志

Inflammatory bowel disease （IBD）， consisting of ulcerative colitis and Crohn's disease， is a chronic relapsing inflammatory gastrointestinal disease closely associated with immune dysfunction. The pathogenesis of IBD is closely related to genetic susceptibility， immune system dysfunction， environmental change， and intestinal microbial dysbiosis. Modern research has found that macrophage polarization plays an important role in the development of IBD and can affect the level of inflammatory response， intestinal mucosal repair， and intestinal microbial balance， making it a potential target for IBD treatment. Increasing evidence suggests that traditional Chinese medicine and its active components can regulate macrophage polarization through multiple pathways and balance the M1/M2 macrophage ratio， thus inhibiting inflammatory response， promoting intestinal mucosal repair， and slowing down the progression of IBD. This article summarized the biological processes and targets involved in macrophage polarization and discussed its impact on IBD. It also provided a brief overview of the latest research on how traditional Chinese medicine and its active components can improve IBD by regulating macrophage polarization， so as to provide new directions and strategies for the clinical application of traditional Chinese medicine in IBD treatment.

Identification of mixed medicinal powder of Epimedii Folium with different origins based on pyrosequencing technology / 药学学报

There are many multi-original medicinal materials in Chinese Pharmacopoeia, and the mixed use of medicinal materials from different sources is common, which has certain influence on the stability of clinical medication. In this study, pyrosequencing technology was used to screen species-specific single nucleotide polymorphisms (SNP) from commonly used DNA barcode sequences, and a rapid and accurate molecular identification method for original species in mixed medicinal powder of Epimedii Folium was established. Multiple sequence alignment analysis showed that the 176th (C/T) mutation and the 196th (A/G) mutation of ITS, the 123rd (C/G) mutation of matK and the 892nd (A/C) mutation of rbcL could be used as the unique SNPs of E. sagittatum, E. koreanum, E. brevicornu and E. pubescens, respectively. In this study, the applicability of pyrosequencing and Sanger sequencing methods in the sequencing of mixture samples was investigated from the perspective of sensitivity and stability. Pyrosequencing method has higher detection sensitivity than Sanger sequencing method for low content samples in the mixed samples. Stability analysis showed that pyrosequencing technology could still obtain effective sequencing results for the amplified products of template DNA after 45 min of 95 ℃ high temperature water bath, while the critical point of Sanger sequencing method was 30 min. In this study, a new identification technology of Epimedii Folium mixed powder primordial species based on pyrosequencing and specific SNP was developed, which can quickly and accurately identify the mixed use of Epimedii Folium with high sensitivity and stability, and can also support the identification of different primordial species and mixed powder primordial herbs, which is conducive to ensuring the consistency and stability of clinical medication.

Comparing Arsenic-Containing Qinghuang Powder and Low-Intensity Chemotherapy in Elderly Patients with Acute Myeloid Leukemia / 中国结合医学杂志

OBJECTIVE@#To compare the clinical effect of arsenic-containing Qinghuang Powder (QHP) and low-intensity chemotherapy (LIC) in treatment of elderly acute myeloid leukemia (eAML) patients.@*METHODS@#Clinical data of 80 eAML patients treated at Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2015 to December 2020 were retrospectively analyzed. The treatment scheme was designed by real world study according to patients' preference, and patients were divided into a QHP group (35 cases) and a LIC group (45 cases). The median overall survival (mOS), 1-, 2-, and 3-year OS rates, and incidence of adverse events were compared between the two groups.@*RESULTS@#The mOS of 80 patients was 11 months, and the 1-, 2-, and 3-year OS rates were 45.51%, 17.96%, and 11.05%, respectively. The QHP and LIC groups demonstrated no significant difference in mOS (12 months vs. 10 months), 1- (48.57% vs. 39.65%), 2- (11.43% vs. 20.04%), and 3-year OS rates (5.71% vs. 13.27%, all P>0.05). Moreover, the related factors of mOS demonstrated no significant difference in patients with age>75 years (11 months vs. 8 months), secondary AML (11 months vs. 8 months), poor genetic prognosis (9 months vs. 7 months), Eastern Cooperative Oncology Group performance status score ⩾ 3 (10 months vs. 7 months) and hematopoietic stem cell transplant comorbidity index ⩾ 4 (11 months vs. 7 months) between the QHP and LIC groups (all P>0.05). However, the incidence of myelosuppression was significantly lower in the QHP group than that in the LIC group (28.57% vs. 73.33%, P<0.01).@*CONCLUSIONS@#QHP and LIC had similar survival rates in eAML patients, but QHP had a lower myelosuppression incidence. Hence, QHP can be an alternative for eAML patients who do not tolerate LIC.

Application of dynamic contrast enhanced status in multiparametric magnetic resonance imaging for prostatic cancer with PI-RADS 4 lesion / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the diagnostic value of dynamic contrast enhanced (DCE) of multiparametric magnetic resonance imaging (mpMRI) for prostate imaging reporting and data system (PI-RADS) 4 lesion in prostate peripheral zone.@*METHODS@#The clinical data of patients with PI-RADS 4 lesion in prostate peripheral zone who underwent prostate biopsy from January 2018 to September 2021 in Peking University First Hospital were retrospectively included. According to DCE status, the patients were divided into the conventional group (4 points for diffusion-weighted imaging) and the comprehensive group (3 points for diffusion-weighted imaging + 1 point for DCE positive). Pearson's chi-square test or Fisher's exact test for comparison was conducted between prostate cancer and non-cancer patients. Univariate and multivariate Logistic regression were performed to analyze the correlation of positive biopsy with age, total prostate specific antigen (PSA), free PSA/total PSA (f/tPSA), prostate volume (PV), PSA density (PSAD) and DCE status.@*RESULTS@#Among the 267 prostate biopsy patients, 217 cases were diagnosed as prostatic cancer (81.27%) and 50 cases were non-cancer (18.73%). Statistical analysis between the prostatic cancer group and the non-cancer group showed that there were significant differences in age, tPSA, PV and PSAD (all P < 0.05), but no significant differences in f/tPSA between the two groups. About different PI-RADS 4 lesion groups, the conventional group and the comprehensive group showed significant difference in biopsy results (P=0.001), and the conventional group had a higher positive rate. The PV of comprehensive group was larger than that of the conventional group. Among the prostate cancer patients diagnosed by biopsy, statistical analysis between the conventional group and comprehensive group showed that there were not significant differences in International Society of Urological Pathology (ISUP) grade and distinguishing clinically significant prostate cancer (all P > 0.05). Logistic univariate analysis showed that the diagnosis of prostate cancer was related to age, tPSA, f/tPSA, PV and DCE group status (all P < 0.05). Multivariate analysis showed that age, tPSA, PV and DCE group status (all P < 0.05) were independent risk factors for the diagnosis of prostatic cancer.@*CONCLUSION@#tPSA, f/tPSA, PV and PSAD are the indicators to improve the diagnosis of prostatic cancer with PI-RADS 4 lesion in peripheral zone lesions. DCE status is worth considering, so that we can select patients for biopsy more accurately, reduce the rate of missed diagnosis of prostate cancer as well as avoid unnecessary prostate puncture.

Diagnostic efficacy of prostate cancer using targeted biopsy with 6-core systematic biopsy for patients with PI-RADS 5 / 北京大学学报(医学版)

OBJECTIVE@#To investigate the diagnostic efficacy of targeted biopsy (TBx), systematic biopsy (SBx), TBx+6-core SBx in prostate cancer (PCa) / clinically significant prostate cancer (cs-PCa) for patients with prostate imaging reporting and data system (PI-RADS) score of 5, and thereby to explore an optimal sampling scheme.@*METHODS@#The data of 585 patients who underwent multiparametric magnetic resonance imaging (mpMRI) with at least one lesion of PI-RADS score 5 at Peking University First Hospital from January 2019 to June 2022 were retrospectively analyzed. All patients underwent mpMRI / transrectal ultrasound (TRUS) cognitive guided biopsy (TBx+SBx). With the pathological results of combined biopsy as the gold standard, we compared the diagnostic efficacy of TBx only, SBx only, and TBx+6-core SBx for PCa/csPCa. The patients were grouped according to mpMRI T-stage (cT2, cT3, cT4) and the detection rates of different biopsy schemes for PCa/csPCa were compared using Cochran's Q and McNemar tests.@*RESULTS@#Among 585 patients with a PI-RADS score of 5, 560 (95.7%) were positive and 25(4.3%) were negative via TBx+SBx. After stratified according to mpMRI T-stage, 233 patients (39.8%) were found in cT2 stage, 214 patients (36.6%) in cT3 stage, and 138 patients (23.6%) in cT4 stage. There was no statistically significant difference in the detection rate of PCa/csPCa between TBx+6-core SBx and TBx+SBx (all P>0.999). Also, there was no statistically significant difference in the detection rate of PCa/csPCa between TBx and TBx+SBx in the cT2, cT3, and cT4 subgroups (PCa: P=0.203, P=0.250, P>0.999; csPCa: P=0.700, P=0.250, P>0.999). The missed diagnosis rate of SBx for PCa and csPCa was 2.1% (12/560) and 1.8% (10/549), and that of TBx for PCa and csPCa was 1.8% (10/560) and 1.4% (8/549), respectively. However, the detection rate of TBx+6-core SBx for PCa and csPCa was 100%. Compared with TBx+SBx, TBx and TBx+6-core SBx had a fewer number of cores and a higher detection rate per core (P < 0.001).@*CONCLUSION@#For patients with a PI-RADS score of 5, TBx and TBx+6-core SBx showed the same PCa/csPCa detection rates and a high detection rates per core as that of TBx+SBx, which can be considered as an optimal scheme for prostate biopsy.

Research advances in hemorrhage after endoscopic retrograde cholangiopancreatography / 临床肝胆病杂志

Although hemorrhage after endoscopic retrograde cholangiopancreatography （ERCP） is mostly mild and self－limited， sometimes blood transfusion and endoscopic hemostasis are still needed. However， rebleeding may occur after conventional endoscopic hemostasis and thus requires interventional vascular embolization or surgical intervention， which might significantly increase the risk of death associated with post－ERCP bleeding. This article discusses the risk factors for post－ERCP bleeding， including disease－specific factors， patient－related factors， and operation－related factors， and elaborates on different measures for the prevention and treatment of post－ERCP bleeding， so as to provide a reference for identifying the high－risk population for bleeding and developing precise surgical strategies in clinical practice.

Study on Mechanism of Linggan Wuwei Jiangxintang in Treating Acute Lung Injury / 中国实验方剂学杂志

ObjectiveTo explore the action mechanism of Linggan Wuwei Jiangxintang on the treatment of lipopolysaccharide （LPS）-induced acute lung injury （ALI） in mice. MethodTraditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， GeneCards， DisGeNET， and Herb databases were combined with clinical data from Gene Expression Omnibus （GEO） to screen the key targets of Linggan Wuwei Jiangxintang in the treatment of ALI. The protein-protein interaction （PPI） network was constructed to screen the core targets， and gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analyses were performed. The mouse ALI model was established by LPS induction to verify the effect and key targets of Linggan Wuwei Jiangxintang on the treatment of ALI. The expression levels of Toll-like receptor 4 （TLR4）， nuclear transcription factor-κB p65 （NF-κB p65）， and phosphorylated NF-κB p65 （NF-κB p-p65） in lung tissue were detected by Western blot. ResultThe analysis showed that the treatment of ALI with Linggan Wuwei Jiangxintang was related to 10 core targets such as interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and JUN， involving TNF signaling pathway， Toll-like receptor signaling pathway， NF-κB signaling pathway， etc. The animal experimental results show that Linggan Wuwei Jiangxintang can reduce lung injury， improve the pathological state of ALI mice， significantly reduce the expression of TNF-α and IL-6 in serum， increase the activity of total superoxide dismutase （T-SOD） and catalase （CAT） in lung tissue， and reduce the expression levels of JUN， TLR4， NF-κB p65， and NF-κB p-p65 proteins in lung tissue. ConclusionLinggan Wuwei Jiangxintang can inhibit LPS-induced inflammation and oxidative damage in ALI mice， and its mechanism may be related to the inhibition of TLR4/NF-κB signaling pathway and the reduction of inflammatory factors such as TNF-α and IL-6.

Intervention of Traditional Chinese and Western Medicine in NLRP3 Inflammasome-mediated Digestive System Diseases： A Review / 中国实验方剂学杂志

The aberrant activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 （NLRP3） inflammasome as an essential component of the innate system is implicated in the pathogenesis of several human inflammatory diseases. Studies have confirmed its association with digestive system diseases such as ulcerative colitis， Crohn's disease， and acute pancreatitis， suggesting that the NLRP3 inflammasome plays a role in the initiation and progression of these diseases. Based on the mechanism of NLRP3 inflammasome activation and the pathways that mediate the inflammatory response， this article introduced the relationship between the NLRP3 inflammasome and the pathogenesis of multiple digestive system diseases and the Chinese and western medical therapies. Traditional Chinese medicine （TCM） has demonstrated definite effects on the NLRP3 inflammasome-mediated digestive system diseases. Some single Chinese medicines or TCM prescriptions can treat digestive system diseases by activating or inhibiting NLRP3 inflammasome activation. NLRP3 inflammasome can receive a variety of endogenous and exogenous stimulatory signals， which can initiate， activate， and mediate inflammatory responses. The inflammasome formation and downstream inflammatory cytokines are involved in not only the inflammatory responses but also the development and progression of multiple digestive system diseases. Therefore， the NLRP3 inflammasome can serve as an ideal target for disease treatment. The future rediscovery and in-depth studies of multiple inflammasomes will shed new light on the treatment of multiple digestive system diseases.

The effect and mechanism of anwulignan on improving hepatic fibrosis in rats / 中国药房

OBJECTIVE To investigate the effect and mechanism of anwulignan on improving hepatic fibrosis in rats. METHODS Fifty SD rats were randomly divided into the normal group， model group， colchicine tablet group （0.1 mg/kg）， and anwulignan high-dose and low-dose groups （2.8 and 0.7 mg/kg）， with 10 rats in each group. Except for the normal group， all groups of rats were intraperitoneally injected with 50% CCl4 olive oil mixed solution to replicate the rat model of liver fibrosis. At the end of the modeling， rats in each group were given the corresponding drugs or distilled water intragastrically from the 9th week， once a day， for 4 weeks consecutively. During the experimental period， the general condition of the rats was observed； the liver index was calculated； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， superoxide dismutase （SOD） and malondialdehyde （MDA） were detected by colorimetric assay； the pathomorphology of the liver tissues and liver fibrosis were observed by HE staining and Masson staining； Western blot was used to detect the expression levels of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway and apoptosis-related proteins in liver tissues. RESULTS Compared with the normal group， the dietary amount of rats in the model group decreased， with sparse and disheveled fur， slow response， and a slower rate of weight growth or weight loss； the liver index was significantly increased （P＜0.01）； the serum levels of ALT， AST and MDA were significantly increased， and the SOD level was significantly decreased （P＜0.01）； HE and Masson staining showed that a large amount of fibrous proliferation was present in the liver tissues of the rats， and the collagen volume fraction was significantly increased （P＜0.01）； the protein expressions of PI3K， Akt， phosphorylated Akt and B-cell lymphoma （Bcl-2） were down-regulated significantly， while the protein expression of Bcl-2-associated X protein was increased significantly （P＜0.01）. Compared with the model group， the above indexes of the anwulignan high-dose and low-dose groups and the colchicine tablets group were all reversed significantly. CONCLUSIONS Anwulignan may reduce oxidative stress and inhibit hepatocyte apoptosis by activating the PI3K/Akt signaling pathway， and play the role of anti-hepatic fibrosis.

Environmental and meteorological factors on the risk of lipid-abnormal dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the impact of meteorological factors in different environments in the eastern and western regions of China on the incidence of lipid-abnormal dry eye.METHODS: This is a multicenter retrospective study. From March 1, 2021 to February 28, 2022, all patients with dry eye were selected from the ophthalmology clinic of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine and Friendship Hospital of Xinjiang Yili Kazakh Autonomous Prefecture. General data(gender, age, employment and education)and climate data for outdoor environments(temperature, humidity, air quality index and wind)on the day of the visit were collected. Patients who met the inclusion and exclusion criteria were selected. Single factor, multiple factors and nonlinear model analysis were applied to identify environmental factors of lipid-abnormal dry eye in both regions.RESULTS: There was no significant difference in the incidence of lipid-abnormal dry eye between Nanjing and Yili in different seasons. The incidence of lipid-abnormal dry eye in Yili was significantly higher in all seasons than in Nanjing(P&#x0026;#x003C;0.001). The results of univariate research showed that the factors affecting the incidence of lipid-abnormal dry eye were gender, employment, humidity, air quality, and wind. The results of multivariate Logistic regression analysis showed that humidity, temperature and air quality were statistically significant, and remained significant after adjusting for the three confounding factors of age, gender and employment situation. Nonlinear analysis showed that the probability of lipid-abnormal dry eye increased with the decrease of temperature when the temperature was below 10℃; within the range of 10℃～15℃, the probability of lipid-abnormal dry eye tended to stabilize. When the temperature exceeded 15℃, the probability of lipid-abnormal dry eye increased with the increase of temperature. Humidity was negatively correlated with the onset of lipid-abnormal dry eye. As humidity increased, the probability of lipid-abnormal dry eye decreased.CONCLUSIONS: The risk of lipid-abnormal dry eye in Yili is higher than that in Nanjing throughout the four seasons. Humidity, temperature, air quality and other environmental and meteorological factors can all affect the incidence of lipid-abnormal dry eye.

Effects of pressure controlled ventilation-volume guaranteed mode on intraoperative pulmonary ventilation and postoperative pulmonary complications in elderly patients undergoing thoracoscopic lobectomy / 肿瘤研究与临床

Objective:To explore the effects of pressure controlled ventilation-volume guaranteed (PCV-VG) mode on intraoperative pulmonary ventilation and postoperative pulmonary complications (PPC) in elderly patients undergoing thoracoscopic lobectomy.Methods:Sixty patients of American Society of Anesthesiologists (ASA) classification Ⅱor Ⅲ, aged 65-80 years old, with body mass index (BMI) 18-30 kg/m 2, received thoracoscopic lobectomy under general anesthesia from November 2021 to June 2022 in the Second Hospital of Shanxi Medical University were recruited. The patients were divided into PCV-VG and volume-controlled ventilation (VCV) groups using the randomized number table method, with 30 patients in each group. The ventilatory parameters of two-lung ventilation were set to respiratory rate (RR) at 10-12 breaths/min, with a tidal volume (VT) of 8 ml/kg (ideal body weight). The ventilatory parameters of one-lung ventilation (OLV) were set at 12-16 breaths/min, with a VT of 6 ml/kg (IBW). The peak airway pressure (Ppeak), plateau airway pressure (Pplat), driving pressure (ΔP), dynamic lung compliance (Cdyn), end-tidal carbon dioxide (ETCO 2), heart rate (HR), mean arterial pressure (MAP), partial pressure of oxygen (PaO 2) and partial pressure of carbon dioxide (PaCO 2) were obtained at 1 min before OLV (T 0), 30 min after OLV (T 1) and 60 min after OLV (T 2). The incidence and severity of PPC, chest tube duration time and postoperative hospital stay time were recorded. Results:The Ppeak, Pplat and ΔP were higher and Cdyn was lower in both groups at T 1-T 2 than at T 0 (all P<0.001). The Ppeak, Pplat and ΔP were higher and Cdyn was lower in PCV-VG group than in VCV group (all P<0.05). There were no statistical differences in HR, MAP, ETCO 2, PaO 2 and PaCO 2 between the two groups (all P > 0.05). There were no statistical differences in the incidence of PPC [43.3% (13/30) vs. 30.0% (9/30)] and chest tube duration time [(4.4±0.9) d vs. (4.2±1.2) d] between VCV group and PCV-VG group (all P>0.05). Compared with VCV group, the proportion of patients with ≥grade 2 PPC was lower in PCV-VG group [10.0% (3/30) vs. 36.7% (11/30), χ2=5.96, P<0.05]. The postoperative hospital stay time in PCV-VG group was shorter than that in VCV group [(6.4±1.3) d vs. (8.0±1.9) d, t = 4.85, P<0.05]. Conclusions:PCV-VG mode can effectively reduce the severity of PPC, shorten the postoperative hospital stay time and improve the prognosis in elderly patients undergoing thoracoscopic lobectomy.

Effect of microneedling combined with Lumin OX and Brightline in treatment of melasma / 中华医学美学美容杂志

Objective:To observe the clinical efficacy of micro-needle therapy combined with Biotrisse BTS Lumin OX and Biotrisse BTS Brightline in the treatment of melasma.Methods:From September 2019 to June 2021, 80 patients with facial chloasma, aged 28-48 (37.3±4.9) years, were selected from Nanjing Jiangning Guze Clinic. The micro-needle therapy was combined with lumin OX and brightline for 6 times, and the observation time was 120 days. The mMASI score and VISIA photos before and after treatment were used to improve the results.Results:Eighty patients with refractory melasma on the face were treated with micro-needle therapy for 7 times (1 time per week for the first 5 times, and twice a week for the 9th and 10th weeks). The photos before and after treatment were compared and the mMASI of the patients' facial chloasma was compared. The scores were analyzed statistically, and the melasma were improved to varying degrees. Before treatment, the mMASI score was 5.4±3.22; 90 days later, the mMASI was 3.22±2.16, and the score decreased significantly ( t=5.9, P<0.05); after 120 days, mMASI score was 1.6±0.68, and the score decreased significantly ( t=7.55, P<0.05). Pigmentation occurred in one patient after treatment, and hypopigmentation after repair treatment; none of the patients had adverse reactions such as hypopigmentation. All the 80 patients had different degrees of improvement in pores and skin texture. Conclusions:The combination of micro-needling with lumin OX and brightline in the treatment of chloasma has a definite effect without obvious side effects. It provides a new method for the treatment of chloasma.

Survey on the views of general practitioners on developing special interests in the context of county medical community / 中华全科医师杂志

Objective:To explore the views of general practitioners (GPs) on developing special interests in the context of the county medical community.Methods:A survey was conducted using self-designed questionnaire from November and December 2019, among 49 general practice residents trained in the First Affiliated Hospital of Zhejiang University School of Medicine. Meanwhile, structured interviews were undertaken with 14 general practice residents.Results:Forty-nine valid questionnaires were collected with a response rate of 100.0%. All participants were from the county medical community units. The survey showed that 91.8% (45/49) of respondents were willing to develop special interests and 79.6% (39/45) chose one subject, and the top three subjects were endocrinology, gastroenterology and cardiology. The structured interviews demonstrated that most participants did not understand meaning of general practitioners with special interests (GPwSIs) clearly and were unable to distinguish GPwSIs from specialists; they were confused about the status, training mode, and assessment standards of GPwSIs. The interviews also showed that the demand for developing special interests for them was derived from the needs of patients for diagnosis and treatment, the target population of health care services, peer advice and personal interests.Conclusions:Most general practice residents are willing to develop special interests, and internal medicine is the first choice; however, their understanding of the GPwSIs is insufficient. The survey suggests that the position, training model, assessment and certification of GPwSI need to be further clarified.