1.Interleukin-1β as target to induce synthetic lethality in KRAS mutant biliary tract cancer
Shijie LI ; Yukai SHAN ; Tianen CHEN ; Win TOPATANA ; Sarun JUENGPANICH ; Ziyi LU ; Yuchao SUN ; Tianao XIE ; Ruijing RUIJING ; Lidan HOU ; Jiang CHEN ; Guojun CHEN ; Jiemin LV ; Xianjue MA ; Pengjuan GUO ; Dan Gabriel DUDA ; Xiujun CAI ; Mingyu CHEN
Clinical and Molecular Hepatology 2026;32(2):904-918
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.
2.The molecular mechanism of electroacupuncture′s phenotypic transformation of middle cerebral artery smooth muscle cells
Linling CHEN ; Xiumei YIN ; Jiawei HAN ; Jiangpeng CAO ; Lanyu JIA ; Jiemin SHI ; Yuanhao DU
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(8):687-692
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.
3.Comparison of the efficacy and safety of nanomicroneedle- versus ultrasound-mediated delivery of tranexamic acid for the treatment of melasma: a randomized controlled study
Jiemin ZHONG ; Wei LI ; Shujuan ZHANG ; Yan YANG ; Rujun XUE ; Xinyi LI ; Yanan KE ; Xiaoyin CHEN ; Quan CHEN
Chinese Journal of Dermatology 2025;58(9):829-833
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.
4.Comparison of the efficacy and safety of nanomicroneedle- versus ultrasound-mediated delivery of tranexamic acid for the treatment of melasma: a randomized controlled study
Jiemin ZHONG ; Wei LI ; Shujuan ZHANG ; Yan YANG ; Rujun XUE ; Xinyi LI ; Yanan KE ; Xiaoyin CHEN ; Quan CHEN
Chinese Journal of Dermatology 2025;58(9):829-833
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.
5.Research progress on the pathogenesis of functional constipation
Jiemin HUANG ; Liangliang LI ; Zhiqiang WU ; Junyi CHEN ; Kai LIN ; Kangwen CHENG
Chinese Journal of General Surgery 2025;34(10):2212-2220
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.
6.Complication profiles of different surgical repair techniques for donor sites following lingual mucosa graft harvesting: a comparative study
Song LI ; Jiemin SI ; Xuxiao XIE ; Wenxiong SONG ; Zuowei LI ; Fangmin CHEN ; Kai LI ; Yinglong SA
Chinese Journal of Urology 2025;46(8):611-616
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.
7.Research progress on the pathogenesis of functional constipation
Jiemin HUANG ; Liangliang LI ; Zhiqiang WU ; Junyi CHEN ; Kai LIN ; Kangwen CHENG
Chinese Journal of General Surgery 2025;34(10):2212-2220
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.
8.Complication profiles of different surgical repair techniques for donor sites following lingual mucosa graft harvesting: a comparative study
Song LI ; Jiemin SI ; Xuxiao XIE ; Wenxiong SONG ; Zuowei LI ; Fangmin CHEN ; Kai LI ; Yinglong SA
Chinese Journal of Urology 2025;46(8):611-616
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.
9.The molecular mechanism of electroacupuncture′s phenotypic transformation of middle cerebral artery smooth muscle cells
Linling CHEN ; Xiumei YIN ; Jiawei HAN ; Jiangpeng CAO ; Lanyu JIA ; Jiemin SHI ; Yuanhao DU
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(8):687-692
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.
10.A multicenter, randomized, controlled study on the treatment of pediatric influenza (wind-heat invading lung) with Qingxuan Zhike granules
Xi MING ; Xiaodong SHEN ; Jinni CHEN ; Jinya WANG ; Jiemin WANG ; Fengzhan CHEN ; Huiping SHEN ; Huihui HUANG ; Yingzhu LU ; Jialin ZHENG ; Ziwei WANG ; Ji BIAN ; Zihao FENG ; Naichao FENG ; Siqi CHEN ; Xunzhou LIU ; Xiaohua YAN ; Xiaoyan WANG ; Wen XIE ; Lei XIONG
Chinese Journal of Applied Clinical Pediatrics 2024;39(8):597-601
Objective:To evaluate the efficacy and safety of Qingxuan Zhike granules in improving cough symptoms and shortening the course of influenza (wind-heat invading lung) in children.Methods:In this multicenter, randomized, controlled clinical trial, a total of 240 outpatient influenza patients from 7 hospitals, including the First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, from April 2023 to December 2023 were collected.The subjects were randomly divided into the control group and the experimental group via SAS software using the block randomization method.The differences between two groups were compared with t test, corrected t test and χ2 test.Subjects in the control group were given Oseltamivir phosphate granules, orally, twice a day (weight ≤15 kg, 30 mg/time; weight >15-23 kg, 45 mg/time; weight >23-40 kg, 60 mg/time; weight >40 kg, 75 mg/time; age≥13 years, 75 mg/time).In addition to Oseltamivir phosphate granules, subjects in the experimental group were also given Qingxuan Zhike granules, orally, 3 times a day (1-3 years old, 1/2 bag each time; >3-6 years old, 3/4 bag each time; >6-14 years old, 1 bag each time).After 5 days of treatment, the medication was suspended for 2 days.The effect of cough, antipyretic effect, clinical recovery rate, clinical recovery time, Canadian Acute Respiratory Illness and Flu Scale (CARIFS) score, traditional Chinese medicine (TCM) syndrome effect, complication rate, and adverse reactions were evaluated between the two groups. Results:Finally, 232 cases were included in the study, including 115 cases in the experimental group and 117 cases in the control group.Before and after treatment, there were no significant difference in CARIFS cough score between the experimental group and the control group (all P>0.05).After treatment, the change in CARIFS cough score in the experimental group [(-1.00±0.91) scores]was significantly higher than that in the control group [(-0.75±0.98) scores] ( t=-1.995, P=0.047).After treatment, the change in TCM syndrome cough score in the experimental group [(-1.69±1.51) scores] was significantly higher than that in the control group [(-0.97±1.63) scores] ( t′=-0.035, P=0.001).The time of complete regression of fever in the experimental group [(44.82±22.72) h] was shorter than that in the control group [(51.35±27.07) h], and the difference between the two groups was statistically significant ( t=-1.966, P=0.050).The fever score showed that the area under the curve between the CARIFS symptom fever score and time in the experimental group was 4.40±2.42, while that in the control group was 5.12±2.44, and the difference between the two groups was statistically significant ( t=-2.252, P=0.025).The clinical recovery rate was 93.91%(108/115) in the experimental group and 92.31%(108/117) in the control group, and there was no significant difference between the two groups ( χ2=0.233, P>0.05).The clinical recovery time in the experimental group [(2.93±1.21) d] was shorter than that in the control group [(3.29±1.15) d], and the difference between the two groups was statistically significant ( t=-2.279, P=0.024).After treatment, there was a significant difference in TCM syndrome score variation between the experimental group [(-12.00±4.13) scores] and the control group [(-10.85±4.31) scores] ( t′=-2.067, P=0.040).No complication occurred in both groups, and there was no significant difference in the incidence of adverse events between the two groups ( χ2=1.299, P>0.05). Conclusions:Qingxuan Zhike granules combined with Oseltamivir phosphate can effectively improve the cough symptoms associated with influenza in children, shorten the time and course of fever, and improve the TCM syndrome score; thus, they are safe in clinical application.

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