Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Objective:To observe the effect of electroacupuncture at the Shuigou point on systolic phenotype-related factors and on the JAK1/STAT3 signaling pathway of the middle cerebral artery smooth muscle cells in rats modeling cerebral infarction; and to explore the molecular mechanism of treating cerebral infarction with electroacupuncture.Methods:A total of 108 healthy male Wistar rats were randomly divided into a blank group ( n=6), a sham operation group ( n=6), a model group ( n=48) and an electroacupuncture group ( n=48). The model and electroacupuncture groups were randomly divided into eight phase subgroups at 1h, 3h, 6h, 12h, 24h, 72h, 7d and 14d after the modeling of middle cerebral artery occlusion (MCAO), with six rats in each group. The electroacupuncture groups received electric acupuncture at the Shuigou acupoint for 20min after successful modeling. Neurological Severity scoring (NSS) was used to evaluate the neurological impairment. PLN protein expression in the middle cerebral artery and the expression of JAK1 and STAT3 proteins in the rats′ brain tissue were detected using western blotting. PDGF-AA content in the middle cerebral artery was measured using enzyme-linked immunosorbent assays. Results:Compared with the blank and sham operation groups, the average NSS score and PDGF-AA protein expression had increased significantly in the model and electroacupuncture groups. PLN protein expression had decreased significantly at 12h-14d in the model group, but decreased significantly at 12h-7d in the electroacupuncture group. Compared with those two groups, there was a significant increase in JAK1 protein expression at 1h-72h, 3h-6h, 24h-72h, and14d in the model group. In the electroacupuncture group the corresponding significant increases were over 1h-14d, 1h-6h, 24h, 72h, and 14d. STAT3 protein expression had increased significantly in the model group over 6h-14d and 3h-14d. In the electroacupuncture group those increases were over 6h-14d. Compared to the model group, a significant increase was observed in the expression of PLN protein at 14d, with a significant decrease in NSS at 72h, 7d and 14d. PDGF-AA protein had increased significantly at 6h-7d. For JAK1 protein that was at 12h and 14d, and for STAT3 protein it was over 12h-72h and at 14d.Conclusion:Electroacupuncture at the Shuigou point may regulate the expression of PDGF-AA and the JAK/STAT signaling pathway so as to regulate the normal expression of PLN, and thus smooth muscle contraction to maintain the normal functioning of the middle cerebral artery. This may be one of the molecular mechanisms by which electroacupuncture at the Shuohui point improves nerve functioning in treating cerebral infarction.

Objective:To compare postoperative complications between acellular dermal matrix（ADM）and direct suture for tongue mucosa defect repair during lingual mucosa urethroplasty.Methods:A retrospective analysis was conducted on 106 patients with anterior urethral stricture who underwent lingual mucosal urethroplasty at the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2022 to July 2024. According to the needs of urethral reconstruction，lingual mucosa was harvested（graft length 0.5 cm longer than the stricture length）. Using an instrumental variable method based on the surgeon’s preference，the tongue wound was repaired either with ADM or direct suture. The ADM group included 56 patients，aged（46.2±18.7）years；diabetes in 8 cases（14.3%），hypertension in 15 cases（26.8%），cardiopulmonary dysfunction in 3 cases（5.3%）；stricture location：penile segment in 44 cases（78.6%），penoscrotal junction in 12 cases（21.4%）；etiology：lichen sclerosus in 8 cases（14.3%），urethritis in 8 cases（14.3%），trauma in 24 cases（42.9%），and re-stricture after hypospadias surgery in 16 cases（28.6%）；maximum urinary flow rate（5.8±2.9）ml/s；graft length（4.02±1.72）cm. The direct suture group included 50 patients，aged（45.8±19.2）years；diabetes in 6 cases（12.0%），hypertension in 12 cases（24.0%），cardiopulmonary dysfunction in 2 cases（4.0%）；etiology：lichen sclerosus in 6 cases（12.0%），urethritis in 8 cases（16.0%），trauma in 25 cases（50.0%），and re-stricture after hypospadias surgery in 11 cases（22%）；stricture location：penile segment in 36 cases（72.0%），penoscrotal junction in 14 cases（28.0%）；maximum urinary flow rate（6.2±3.1）ml/s；graft length（4.18±1.68）cm. There were no statistically significant differences in the above baseline characteristics between the two groups（ P>0.05）.ADM group after electrocautery hemostasis，an ADM patch tailored to the wound size was used to cover the donor site. The edges of the ADM were overlapped with the wound margin and sutured to the submucosal layer using interrupted 4-0 polyglactin sutures. Direct suture group after electrocautery hemostasis，the wound was stretched into a diamond shape and closed in layers by suturing the mucosal layer down to the muscle layer using interrupted 4-0 polyglactin sutures. The primary outcome measures were postoperative tongue complications including hemorrhage，hematoma，and infection（Clavien-Dindo classification）. Secondary outcomes included VAS pain scores，functional recovery（difficulty drinking，difficulty eating，speech impairment，limited mouth opening），and sensory recovery（sensory disturbance，taste disturbance）. Results:The follow-up period ranged from 6 to 24 months，with a mean of 9.2 months. The 6-month follow-up rate was 100%. No Clavien-Dindo grade Ⅲ or higher complications（hemorrhage，hematoma，infection）occurred by the end of follow-up. Regarding secondary outcomes，the VAS pain score on postoperative day 1 was significantly better in the ADM group than in the suture group［0（0，3）vs. 2（0，3），P=0.013］.Functional impact：The incidence of difficulty drinking［24 cases（42.9%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 21 cases（42.0%）］，difficulty eating［20 cases（35.7%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 27 cases（54.0%）］，and speech impairment［20 cases（35.7%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 27 cases（54.0%）］on postoperative day 1，day 7，and within the first month，respectively，was significantly lower in the ADM group（all P<0.05）. On postoperative day 1 and day 7，the incidence of limited mouth opening was higher in the ADM group［0 cases vs. 6 cases（12.0%），0 cases vs. 6 cases（12.0%）］（ P<0.05）.Sensory recovery：The incidence of taste disturbance was higher in the ADM group at 7 days［8 cases（14.3%）vs. 0 cases］，1 month［8 cases（14.3%）vs. 0 cases］，and 3 months［8 cases（14.3%）vs. 0 cases］postoperatively（ P<0.05）. The incidence of sensory disturbance was higher in the ADM group at 1 day［20 cases（35.7%）vs. 6 cases（12.0%）］，7 days［16 cases（28.6%）vs. 6 cases（12.0%）］，and 1 month［16 cases（28.6%）vs. 6 cases（12.0%）］postoperatively（ P<0.05）. Pain scores and complication rates were zero in both groups after 6 months. Conclusions:ADM repair improves early recovery but may increase transient sensory complications. Both methods are safe for clinical application.

Functional constipation is a common functional gastrointestinal disorder with a multifactorial and incompletely understood pathogenesis.Recent studies have revealed that its development involves the interplay of multiple mechanisms,including neurogenic and myogenic dysfunction of the colon,reduction and impairment of interstitial cells of Cajal(ICCs),outlet obstruction,dysregulation of the gut-brain axis,immune activation,and gut microbiota imbalance.Slow-transit constipation is mainly associated with enteric neural abnormalities,disruption of ICC signaling,and inflammation,whereas outlet obstruction constipation often results from pelvic floor dysfunction and rectal hyposensitivity.Dysregulation of the gut-brain axis plays a central role,involving impaired central regulation,hormonal imbalance,and enhanced local immune response.Additionally,gut microbial metabolites such as short-chain fatty acids,bile acids,and methane affect colonic motility and inflammation.This review summarizes the current understanding and research progress on the pathogenesis of functional constipation,providing insights for mechanism-based and individualized therapeutic approaches.

Objective:To compare the clinical efficacy and safety of nanomicroneedle- versus ultrasound-mediated delivery of tranexamic acid for the treatment of melasma.Methods:A prospective, randomized, controlled study was conducted. Patients with melasma were collected from the Department of Dermatology, Guangzhou Dermatology Hospital from March 2023 to May 2024, and divided into a nanomicroneedle group (receiving nanomicroneedle-mediated delivery of tranexamic acid) and an ultrasound group (receiving ultrasound-mediated delivery of tranexamic acid) using the random number table method. Both groups underwent the treatment once a week for a total of 8 sessions. At week 12, outcomes including melasma area and severity index (MASI) scores, treatment response rates, VISIA brown spot scores, pain scores, and adverse reactions were evaluated and compared between the two groups. Statistical analyses were carried out using two-independent-sample t test, Mann-Whitney U test, and chi-square test. Results:A total of 80 patients with melasma were included, with 40 in each group. In the nanomicroneedle group, the patients were aged 40.35 ± 7.39 years (range: 25 - 55 years), with the disease duration being 8.45 ± 4.77 months (range: 1 - 16 months) ; in the ultrasound group, the patients were aged 40.25 ± 7.76 years (range: 25 - 55 years), and their disease duration was 10.45 ± 5.07 months (range: 2 - 17 months) ; there were no significant differences in ages or disease duration between the two groups (both P > 0.05). At week 12, both groups demonstrated reduced MASI scores compared to baseline scores, and the MASI scores were significantly lower in the nanomicroneedle group ( M[ Q1, Q3]: 5.80[4.20, 9.35]) than in the ultrasound group (8.65[5.70, 10.80], Z = 2.50, P = 0.012). The overall response rate was significantly higher in the nanomicroneedle group (97.5%, 39/40) than in the ultrasound group (55.0%, 22/40; χ2 = 19.95, P < 0.001). The lateral facial VISIA brown spot scores were also significantly lower in the nanomicroneedle group (left side: 126.18 ± 36.54 points; right side: 138.50 ± 40.76 points) than in the ultrasound group (left side: 142.37 ± 32.40 points; right side: 157.13 ± 39.59 points; t = -2.10, -2.07, P = 0.039, 0.041, respectively). In the nanomicroneedle group, the pain scores were 4.12 ± 1.47 points, and varying severity of adverse reactions such as erythema, edema and dryness occurred after operation, all of which resolved spontaneously within 48 hours. No marked adverse reactions were observed in the ultrasound group. Conclusion:Nanomicroneedle-mediated delivery of tranexamic acid demonstrated superior clinical efficacy and favorable safety profiles compared to the ultrasound-mediated delivery, providing more options for the treatment of melasma.

Objective:To compare the clinical efficacy and safety of nanomicroneedle- versus ultrasound-mediated delivery of tranexamic acid for the treatment of melasma.Methods:A prospective, randomized, controlled study was conducted. Patients with melasma were collected from the Department of Dermatology, Guangzhou Dermatology Hospital from March 2023 to May 2024, and divided into a nanomicroneedle group (receiving nanomicroneedle-mediated delivery of tranexamic acid) and an ultrasound group (receiving ultrasound-mediated delivery of tranexamic acid) using the random number table method. Both groups underwent the treatment once a week for a total of 8 sessions. At week 12, outcomes including melasma area and severity index (MASI) scores, treatment response rates, VISIA brown spot scores, pain scores, and adverse reactions were evaluated and compared between the two groups. Statistical analyses were carried out using two-independent-sample t test, Mann-Whitney U test, and chi-square test. Results:A total of 80 patients with melasma were included, with 40 in each group. In the nanomicroneedle group, the patients were aged 40.35 ± 7.39 years (range: 25 - 55 years), with the disease duration being 8.45 ± 4.77 months (range: 1 - 16 months) ; in the ultrasound group, the patients were aged 40.25 ± 7.76 years (range: 25 - 55 years), and their disease duration was 10.45 ± 5.07 months (range: 2 - 17 months) ; there were no significant differences in ages or disease duration between the two groups (both P > 0.05). At week 12, both groups demonstrated reduced MASI scores compared to baseline scores, and the MASI scores were significantly lower in the nanomicroneedle group ( M[ Q1, Q3]: 5.80[4.20, 9.35]) than in the ultrasound group (8.65[5.70, 10.80], Z = 2.50, P = 0.012). The overall response rate was significantly higher in the nanomicroneedle group (97.5%, 39/40) than in the ultrasound group (55.0%, 22/40; χ2 = 19.95, P < 0.001). The lateral facial VISIA brown spot scores were also significantly lower in the nanomicroneedle group (left side: 126.18 ± 36.54 points; right side: 138.50 ± 40.76 points) than in the ultrasound group (left side: 142.37 ± 32.40 points; right side: 157.13 ± 39.59 points; t = -2.10, -2.07, P = 0.039, 0.041, respectively). In the nanomicroneedle group, the pain scores were 4.12 ± 1.47 points, and varying severity of adverse reactions such as erythema, edema and dryness occurred after operation, all of which resolved spontaneously within 48 hours. No marked adverse reactions were observed in the ultrasound group. Conclusion:Nanomicroneedle-mediated delivery of tranexamic acid demonstrated superior clinical efficacy and favorable safety profiles compared to the ultrasound-mediated delivery, providing more options for the treatment of melasma.

Functional constipation is a common functional gastrointestinal disorder with a multifactorial and incompletely understood pathogenesis.Recent studies have revealed that its development involves the interplay of multiple mechanisms,including neurogenic and myogenic dysfunction of the colon,reduction and impairment of interstitial cells of Cajal(ICCs),outlet obstruction,dysregulation of the gut-brain axis,immune activation,and gut microbiota imbalance.Slow-transit constipation is mainly associated with enteric neural abnormalities,disruption of ICC signaling,and inflammation,whereas outlet obstruction constipation often results from pelvic floor dysfunction and rectal hyposensitivity.Dysregulation of the gut-brain axis plays a central role,involving impaired central regulation,hormonal imbalance,and enhanced local immune response.Additionally,gut microbial metabolites such as short-chain fatty acids,bile acids,and methane affect colonic motility and inflammation.This review summarizes the current understanding and research progress on the pathogenesis of functional constipation,providing insights for mechanism-based and individualized therapeutic approaches.

Objective:To compare postoperative complications between acellular dermal matrix（ADM）and direct suture for tongue mucosa defect repair during lingual mucosa urethroplasty.Methods:A retrospective analysis was conducted on 106 patients with anterior urethral stricture who underwent lingual mucosal urethroplasty at the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2022 to July 2024. According to the needs of urethral reconstruction，lingual mucosa was harvested（graft length 0.5 cm longer than the stricture length）. Using an instrumental variable method based on the surgeon’s preference，the tongue wound was repaired either with ADM or direct suture. The ADM group included 56 patients，aged（46.2±18.7）years；diabetes in 8 cases（14.3%），hypertension in 15 cases（26.8%），cardiopulmonary dysfunction in 3 cases（5.3%）；stricture location：penile segment in 44 cases（78.6%），penoscrotal junction in 12 cases（21.4%）；etiology：lichen sclerosus in 8 cases（14.3%），urethritis in 8 cases（14.3%），trauma in 24 cases（42.9%），and re-stricture after hypospadias surgery in 16 cases（28.6%）；maximum urinary flow rate（5.8±2.9）ml/s；graft length（4.02±1.72）cm. The direct suture group included 50 patients，aged（45.8±19.2）years；diabetes in 6 cases（12.0%），hypertension in 12 cases（24.0%），cardiopulmonary dysfunction in 2 cases（4.0%）；etiology：lichen sclerosus in 6 cases（12.0%），urethritis in 8 cases（16.0%），trauma in 25 cases（50.0%），and re-stricture after hypospadias surgery in 11 cases（22%）；stricture location：penile segment in 36 cases（72.0%），penoscrotal junction in 14 cases（28.0%）；maximum urinary flow rate（6.2±3.1）ml/s；graft length（4.18±1.68）cm. There were no statistically significant differences in the above baseline characteristics between the two groups（ P>0.05）.ADM group after electrocautery hemostasis，an ADM patch tailored to the wound size was used to cover the donor site. The edges of the ADM were overlapped with the wound margin and sutured to the submucosal layer using interrupted 4-0 polyglactin sutures. Direct suture group after electrocautery hemostasis，the wound was stretched into a diamond shape and closed in layers by suturing the mucosal layer down to the muscle layer using interrupted 4-0 polyglactin sutures. The primary outcome measures were postoperative tongue complications including hemorrhage，hematoma，and infection（Clavien-Dindo classification）. Secondary outcomes included VAS pain scores，functional recovery（difficulty drinking，difficulty eating，speech impairment，limited mouth opening），and sensory recovery（sensory disturbance，taste disturbance）. Results:The follow-up period ranged from 6 to 24 months，with a mean of 9.2 months. The 6-month follow-up rate was 100%. No Clavien-Dindo grade Ⅲ or higher complications（hemorrhage，hematoma，infection）occurred by the end of follow-up. Regarding secondary outcomes，the VAS pain score on postoperative day 1 was significantly better in the ADM group than in the suture group［0（0，3）vs. 2（0，3），P=0.013］.Functional impact：The incidence of difficulty drinking［24 cases（42.9%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 21 cases（42.0%）］，difficulty eating［20 cases（35.7%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 27 cases（54.0%）］，and speech impairment［20 cases（35.7%）vs. 36 cases（72.0%），16 cases（28.6%）vs. 36 cases（72.0%），8 cases（14.3%）vs. 27 cases（54.0%）］on postoperative day 1，day 7，and within the first month，respectively，was significantly lower in the ADM group（all P<0.05）. On postoperative day 1 and day 7，the incidence of limited mouth opening was higher in the ADM group［0 cases vs. 6 cases（12.0%），0 cases vs. 6 cases（12.0%）］（ P<0.05）.Sensory recovery：The incidence of taste disturbance was higher in the ADM group at 7 days［8 cases（14.3%）vs. 0 cases］，1 month［8 cases（14.3%）vs. 0 cases］，and 3 months［8 cases（14.3%）vs. 0 cases］postoperatively（ P<0.05）. The incidence of sensory disturbance was higher in the ADM group at 1 day［20 cases（35.7%）vs. 6 cases（12.0%）］，7 days［16 cases（28.6%）vs. 6 cases（12.0%）］，and 1 month［16 cases（28.6%）vs. 6 cases（12.0%）］postoperatively（ P<0.05）. Pain scores and complication rates were zero in both groups after 6 months. Conclusions:ADM repair improves early recovery but may increase transient sensory complications. Both methods are safe for clinical application.

Objective:To observe the effect of electroacupuncture at the Shuigou point on systolic phenotype-related factors and on the JAK1/STAT3 signaling pathway of the middle cerebral artery smooth muscle cells in rats modeling cerebral infarction; and to explore the molecular mechanism of treating cerebral infarction with electroacupuncture.Methods:A total of 108 healthy male Wistar rats were randomly divided into a blank group ( n=6), a sham operation group ( n=6), a model group ( n=48) and an electroacupuncture group ( n=48). The model and electroacupuncture groups were randomly divided into eight phase subgroups at 1h, 3h, 6h, 12h, 24h, 72h, 7d and 14d after the modeling of middle cerebral artery occlusion (MCAO), with six rats in each group. The electroacupuncture groups received electric acupuncture at the Shuigou acupoint for 20min after successful modeling. Neurological Severity scoring (NSS) was used to evaluate the neurological impairment. PLN protein expression in the middle cerebral artery and the expression of JAK1 and STAT3 proteins in the rats′ brain tissue were detected using western blotting. PDGF-AA content in the middle cerebral artery was measured using enzyme-linked immunosorbent assays. Results:Compared with the blank and sham operation groups, the average NSS score and PDGF-AA protein expression had increased significantly in the model and electroacupuncture groups. PLN protein expression had decreased significantly at 12h-14d in the model group, but decreased significantly at 12h-7d in the electroacupuncture group. Compared with those two groups, there was a significant increase in JAK1 protein expression at 1h-72h, 3h-6h, 24h-72h, and14d in the model group. In the electroacupuncture group the corresponding significant increases were over 1h-14d, 1h-6h, 24h, 72h, and 14d. STAT3 protein expression had increased significantly in the model group over 6h-14d and 3h-14d. In the electroacupuncture group those increases were over 6h-14d. Compared to the model group, a significant increase was observed in the expression of PLN protein at 14d, with a significant decrease in NSS at 72h, 7d and 14d. PDGF-AA protein had increased significantly at 6h-7d. For JAK1 protein that was at 12h and 14d, and for STAT3 protein it was over 12h-72h and at 14d.Conclusion:Electroacupuncture at the Shuigou point may regulate the expression of PDGF-AA and the JAK/STAT signaling pathway so as to regulate the normal expression of PLN, and thus smooth muscle contraction to maintain the normal functioning of the middle cerebral artery. This may be one of the molecular mechanisms by which electroacupuncture at the Shuohui point improves nerve functioning in treating cerebral infarction.

Objective To investigate the effects of Jianpi Yichang Powder on regulating the NLRP3 inflammasome signaling pathway to inhibit dendritic cells(DCs)inflammatory injury induced by TNF-α;To explore its mechanism in the treatment of ulcerative colitis.Methods C57BL/6 mice DCs were primitively isolated and cultured.The cultured DCs were randomly divided into the normal group,model group,negative control group,positive drug group and TCM group.DCs inflammatory microenvironment model was established by TNF-α induction.After corresponding treatments were given to each group,CCK-8 method was used to detect cell proliferation ability,immunofluorescence and Western blot were used to detect the protein expressions of NLRP3,ASC and Caspase-1 in DCs respectively,Western blot and RT-PCR were used to detect the protein and mRNA expressions of IL-1β and IL-18 in DCs.Results Compared with the normal group,the proliferation ability in DCs of model group significantly decreased(P<0.01),the positive expressions of NLRP3,ASC and Caspase-1 significantly increased,the expressions of NLRP3,ASC,Caspase-1,IL-18,IL-1β protein and IL-18,IL-1β mRNA in DCs significantly increased(P<0.01).Compared with the model group and negative control group,the proliferation ability of DCs significantly increased in positive drug group and TCM group(P<0.01),the positive expressions of NLRP3,ASC,and Caspase-1 significantly decreased(P<0.01),the protein expressions of NLRP3,ASC,Caspase-1,IL-1β and IL-18 significantly decreased(P<0.05,P<0.01),and the mRNA expressions of IL-1β and IL-18 significantly decreased(P<0.01).The cell proliferation ability,Caspase-1 positive expression,and IL-18 mRNA expression of TCM group were significantly higher than those of the positive drug group(P<0.05),while the mRNA expression of IL-1β was lower than that of the positive drug group(P<0.05).Conclusion Jianpi Yichang Powder can inhibit the inflammatory response of DCs induced by TNF-α,and its mechanism in the treatment of ulcerative colitis may be related to regulating the expressions of the NLRP3 inflammasome signaling pathway,including the expressions of NLRP3,ASC,Caspase-1,IL-18 and IL-1β.