This paper summarizes Professor WANG Xixing's clinical experience in treating immune checkpoint inhibitor-related pneumonitis （CIP） based on the theory of "cough attributed to the five zang （脏） organs". Cough is a common predominant symptom of CIP. According to the theory of "cough attributed to the five zang organs"， drug toxicity triggers cancer toxin， leading to disharmony among the five zang organs， and then lung failing to diffuse and govern descent as the core pathogenesis. Therefore， treatment should focus on harmonizing the five zang organs to restore the normal function of lung qi to diffuse and govern descent. In clinical practice， CIP can be classified into four syndrome patterns， including lung yin depletion， deficiency of both the lung and the spleen with phlegm-dampness， liver fire harassing the lung， and lung-kidney yin deficiency. Correspondingly， Chaimai Jinluo Runfei Decoction （柴麦金络润肺汤） is used to nourish yin and moisten the lung； Qigui Peitu Huayin Decoction （芪桂培土化饮汤） is used to fortify the spleen and tonify the lung， resolve dampness and dispel phlegm； Chaidan Shuyu Runjin Decoction （柴丹疏郁润金汤） is used to drain liver and clear the lung； and Dimai Jinshui Xiangsheng Decoction （地脉金水相生汤） is used to nourish the kidney and moisten the lung.

Objective To observe the value of neurite orientation dispersion and density imaging(NODDI)for diagnosing unilateral temporal lobe epilepsy(TLE)complicated with hippocampal sclerosis(HS)(TLE-HS).Methods Brain diffusion kurtosis imaging(DKI),3D T1WI and 3D fluid attenuated inversion recovery(FLAIR)sequence images were prospectively collected in 55 patients with unilateral TLE-HS(TLE-HS group)and 55 healthy controls(HC group),and NODDI parameter maps were acquired.The hippocampus NODDI parameters values and FLAIR signal intensity were compared among the affected side,the healthy side in TLE-HS group and HC group,as well as between each two,and their value for diagnosing unilateral TLE-HS were analyzed.Results Significant differences of hippocampus intracellular volume fraction(ICVF),isotropic volume fraction(ISOVF),orientation dispersion index(ODI)values and FLAIR signal intensity were found among the affected side,the healthy side in TLE-HS group and HC group(all P＜0.05).There were significant differences of ICVF,ISOVF and ODI values between the affected side and the healthy side in TLE-HS group(all P＜0.05),of ICVF,ISOVF,ODI values and FLAIR signal intensity between the affected side in TLE-HS group and HC group(all P＜0.05),and of ISOVF values and FLAIR signal intensity between the healthy side in TLE-HS group and HC group(both P＜0.05).The area under the curve(AUC)of ICVF,ISOVF,ODI and their combination for differentiating the affected side and the healthy side of TLE-HS was 0.913,0.712,0.912 and 0.964,for differentiating the affected side of TLE-HS and HC was 0.940,0.822,0.871 and 0.971,respectively,and the combination both had the highest AUC(both P＜0.05).The AUC of ISOVF,ODI and their combination for differentiating the healthy side of TLE-HS and HC was 0.666,0.630 and 0.744,respectively,being not significant different(all P＞0.05).The AUC of FLAIR signal intensity for differentiating the affected side and the healthy side of TLE-HS,the affected side of TLE-HS and HC,the healthy side of TLE-HS and HC was 0.627,0.756 and 0.653,respectively.Conclusion Bilateral hippocampus NODDI parameters were helpful for diagnosing unilateral TLE-HS,which might be superior to commonly used FLAIR sequence.

Objective To establish a rat model of acclimatization to motion sickness(MS)induced by rotational stimulation.Methods To determine the stimulation conditions of MS,SD rats were divided into a static control group(SCG)and a single rotation stimulation group(SRG)before being subjected to the motion sickness index(MSI)measurement,open-field experiment and Morris water maze experiment after rotational stimulation to verify the feasibility of MS being induced in rats.Morris water maze experiments were performed to find out whether rotational stimulation could be used to induce MS in rats.During experiments on acclimatization,the SD rats were divided into the control group(Ctrl),one day of rotational stimulation group(Day1),three days of continuous rotational stimulation group(Day3),and seven days of continuous rotational stimulation group(Day7)before the changes in the MSI and behavior of these rats were recorded so as to explore the relationship between continuous stimulation and MS acclimatization in rats.Results After rotational stimulation,the rats showed a significant increase in the number of fecal pellets(P<0.0001)and in the MSI(P<0.0001)compared with the SCG.In the open field experiment,the rats showed a significant decrease in the spontaneous activity time(AT)(P<0.0001),total spontaneous activity distance(TD)(P<0.001)and distance moved by the center point per second(DMCPS)(P<0.001).The time taken to climb onto the platform(latency to find the platform,LP)(P<0.0001)and the total distance to the platform(distance to the platform,DP)(P<0.001)were significantly increased during the Morris water maze experiment.Acclimatization experiments revealed a significant increase in MSI and in the number of fecal pellets in the Day1 and Day3 groups of rotational stimulation compared to the Ctrl group(P<0.0001).AT(P<0.01),TD(P<0.05)and DMCPS(P<0.01)were significantly decreased,while LP and DP were significantly increased(P<0.0001),but there was no statistically significant difference in indices compared with the Day7 group(P>0.05).Conclusion Sinusoidal stimulation can induce MS in rats,and twice-a-day,continuous rotational stimulation for seven days can lead to acclimatization.The rat MS model can be assessed via behavioral experiments.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder and its symptoms are subject to the composition of the gut microbiota. However, it is not yet clear how probiotics relieve IBS, and there is no well-acknowledged standards concerning the clinical application of probiotics. This systematic review was conducted on the literature published from January 2020 to December 2023 and included 12 randomized controlled trials on probiotics in the treatment of IBS. Compared with placebo, the probiotic preparations improved the overall efficacy in IBS patients and was also well tolerated, suggesting the potential of probiotics in IBS management. Nevertheless, different probiotic strains, dosages, combinations, and dosing schedules may affect the outcomes. In the future, large-scale, multi-center, long-term follow-up studies are still needed to clarify the effective strains and methods of use and to promote the use of probiotics in the treatment of IBS.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder and its symptoms are subject to the composition of the gut microbiota. However, it is not yet clear how probiotics relieve IBS, and there is no well-acknowledged standards concerning the clinical application of probiotics. This systematic review was conducted on the literature published from January 2020 to December 2023 and included 12 randomized controlled trials on probiotics in the treatment of IBS. Compared with placebo, the probiotic preparations improved the overall efficacy in IBS patients and was also well tolerated, suggesting the potential of probiotics in IBS management. Nevertheless, different probiotic strains, dosages, combinations, and dosing schedules may affect the outcomes. In the future, large-scale, multi-center, long-term follow-up studies are still needed to clarify the effective strains and methods of use and to promote the use of probiotics in the treatment of IBS.

Objective To observe the value of neurite orientation dispersion and density imaging(NODDI)for diagnosing unilateral temporal lobe epilepsy(TLE)complicated with hippocampal sclerosis(HS)(TLE-HS).Methods Brain diffusion kurtosis imaging(DKI),3D T1WI and 3D fluid attenuated inversion recovery(FLAIR)sequence images were prospectively collected in 55 patients with unilateral TLE-HS(TLE-HS group)and 55 healthy controls(HC group),and NODDI parameter maps were acquired.The hippocampus NODDI parameters values and FLAIR signal intensity were compared among the affected side,the healthy side in TLE-HS group and HC group,as well as between each two,and their value for diagnosing unilateral TLE-HS were analyzed.Results Significant differences of hippocampus intracellular volume fraction(ICVF),isotropic volume fraction(ISOVF),orientation dispersion index(ODI)values and FLAIR signal intensity were found among the affected side,the healthy side in TLE-HS group and HC group(all P＜0.05).There were significant differences of ICVF,ISOVF and ODI values between the affected side and the healthy side in TLE-HS group(all P＜0.05),of ICVF,ISOVF,ODI values and FLAIR signal intensity between the affected side in TLE-HS group and HC group(all P＜0.05),and of ISOVF values and FLAIR signal intensity between the healthy side in TLE-HS group and HC group(both P＜0.05).The area under the curve(AUC)of ICVF,ISOVF,ODI and their combination for differentiating the affected side and the healthy side of TLE-HS was 0.913,0.712,0.912 and 0.964,for differentiating the affected side of TLE-HS and HC was 0.940,0.822,0.871 and 0.971,respectively,and the combination both had the highest AUC(both P＜0.05).The AUC of ISOVF,ODI and their combination for differentiating the healthy side of TLE-HS and HC was 0.666,0.630 and 0.744,respectively,being not significant different(all P＞0.05).The AUC of FLAIR signal intensity for differentiating the affected side and the healthy side of TLE-HS,the affected side of TLE-HS and HC,the healthy side of TLE-HS and HC was 0.627,0.756 and 0.653,respectively.Conclusion Bilateral hippocampus NODDI parameters were helpful for diagnosing unilateral TLE-HS,which might be superior to commonly used FLAIR sequence.

Objective To establish a fast,stable,and sensitive zebrafish model of osteoporosis(OP)using different method.Methods OP models were induced by iron overload or prednisolone(Pred),and bone formation and mortality were observed.The groups were divided into:Control group,model group(include FAC group and Pred group),and positive control group(AC group).Ammonium ferric citrate was used as the model drug in the iron-overload induction method.For the Pred induction models,the modeling time for the Pred-3 days post-fertilization(dpf)method was 3～9 dpf,the modeling time for the Pred-5 dpf method was 5～10 dpf,and Pred was administered from 3 dpf and removed from 7～9 dpf for the Pred withdrawal method.To compare the anti-osteoporosis(OP)effects of commonly used drugs such as Alfacalcidol(AC),Calcitriol(CA),and Alendronate(AL),it's important to select a stable and sensitive positive control drug and to further optimize different staining methods and conditions.Results There was no significant effect of ammonium ferric citrate 500 μg/mL on bone formation.Bone formation and the length of the first vertebra were significantly decreased in the Pred group induced by Pred-3 dpf compared with those in the control group(P＜0.01,P＜0.05),but zebrafish mortality was higher.There was no significant difference between the Pred-5 dpf method,but bone formation was significantly reduced in the Pred withdrawal group(P＜0.01),with no mortality.Alfacalcidol,calcitriol,and alendronate all had anti-OP effects,with CA having the most sensitive and stable anti-OP effect.Alizarin red staining showed that the optimal dye parameters were 0.02%concentration for dyeing 2 h,with washing in 0.5%KOH and glycerol under the conditions of a 3∶1 ratio for 3 h followed by a 1∶1 ratio for 14 h.The result of staining showed that calcein was more sensitive for staining bone nodes and ARS staining was more sensitive for staining the first vertebra.Conclusions The Pred withdrawal method can be used to establish a rapid,stable,and sensitive OP model in zebrafish as a reliable model for studying OP.

Objective:To explore the role of interleukin-18 (IL-18) in the pathogenesis of dermatomyositis (DM) associated with positive anti-melanoma differentiation-associated gene 5 antibodies(MDA5-DM).Methods:Twenty-eight cases of MDA5-DM in the department of rheumatology and immunology, the first hospital of Nanjing medical university and the first affiliated hospital od Wannan medical colledge from August 2018 to December 2011 were included in this study, comprising 15 cases with combined rapidly progressive interstitial pneumonia (RPILD) and 13 cases without RPILD (nonRPILD). Additionally, 28 cases of antisynthetase syndrome (ASS) and 28 healthy volunteers (HC) were included for comparison. Clinical, laboratory, and imaging data were collected for both the DM and ASS groups. Serum IL-18 levels were measured using ELISA. Independent t test, Mann-whitney U test, χ2 test and Fisher′s exact probability method were used for analysis. Results:Significant differences were observed in LDH, hydroxybutyrate dehydrogenase (HBDH), ESR, CRP, serum ferritin (SFE), and IL-18 levels between the MDA5-DM group, the ASS group and the HC group ( F=46.65, 43.19, 31.28, 23.94, 30.94, 49.44, all P<0.001). Additionally, lymphocyte counts and hemoglobin levels differed significantly among the three groups( F=35.26, P<0.001; F=18.59, P<0.001). MDA5-DM patients exhibited higher incidences of Gottron′s sign, helitrope rash, periungual erythema, skin ulcers, and RPILD compared to ASS patients ( χ2=20.96, P<0.001; χ2=5.85, P=0.016; χ2=13.69, P<0.001; χ2=9.16, P=0.002; χ2=4.79, P=0.029). However, the incidence of mechanic′s hand was lower in MDA5-DM patients ( χ2=3.90, P=0.048). The level of IL-18 significantly decreased in MDA5-DM after treatment[(104.28(71.96,151.10)pg/ml vs. 78.30(56.20, 94.80)pg/ml, =2.27, P=0.023)]. Similar reductions were observed in the ASS group[(72.30(61.39, 95.94)pg/ml vs. 45.30(29.00,84.10)pg/ml, Z=2.691, P=0.007]. The IL-18 level changes in the MDA5-DM combined with RPILD group were not statistically significant [99.49 (77.65, 130.87)pg/ml vs. 89.40(54.80, 120.20)pg/ml, Z=0.65, P=0.515]. In the MDA5-DM survival group, IL-18 levels decreased significantly after treatment [59.45(53.58, 81.63)pg/ml vs. 106.37(83.62, 152.07)pg/ml, Z=2.80, P=0.005], while the changes in the IL-18 levels of patients in the MDA5-DM death group were not statistically significant [99.49(56.70, 140.15)pg/ml vs. 94.80(71.40, 155.45)pg/ml, Z=1.75, P=0.080]. Conclusion:MDA5-DM patients are different from the ASS patients in clinical manifestations and indicators involved in laboratory tests. The expression level of IL-18 tends to increase during the active phase of MDA5-DM and ASS, and decrease with remission of the disease. MDA5-DM may play an important role in the pathogenesis, and persistent high level of IL-18 is responsible for RPILD and death of MDA5-DM. Sustained high level of IL-18 can be used as a potential biomarker for the estimating development of MDA5-DM into RPILD.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

Particle size and surface properties are crucial for lymphatic drainage(LN),dendritic cell(DC)uptake,DC maturation,and antigen cross-presentation induced by nanovaccine injection,which lead to an effective cell-mediated immune response.However,the manner in which the particle size and surface properties of vaccine carriers such as mesoporous silica nanoparticles(MSNs)affect this immune response is un-known.We prepared 50,100,and 200 nm of MSNs that adsorbed ovalbumin antigen(OVA)while modifying β-glucan to enhance immunogenicity.The results revealed that these MSNs with different particle sizes were just as efficient in vitro,and MSNs with β-glucan modification demonstrated higher efficacy.However,the in vivo results indicated that MSNs with smaller particle sizes have stronger lymphatic targeting efficiency and a greater ability to promote the maturation of DCs.The results also indicate that β-glucan-modified MSN,with a particle size of-100 nm,has a great potential as a vaccine delivery vehicle and immune adjuvant and offers a novel approach for the delivery of multiple thera-peutic agents that target other lymph-mediated diseases.