1.Effect of Modified Shoutai Pill (寿胎丸加味方) on Inflammatory Reaction and Expression of Endometrial Receptivity-Related Factors in A Rat Model of Polycystic Ovary Syndrome and Miscarriage with High Testosterone-Insulin Resistance
Tingting GUO ; Meng JIANG ; Huaiying YANG ; Xiang JI ; Yuehui ZHANG
Journal of Traditional Chinese Medicine 2025;66(3):275-282
ObjectiveTo explore the possible mechanisms of Modified Shoutai Pill (寿胎丸加味方, MSP) in treating polycystic ovary syndrome (PCOS) with hyperandrogenism, insulin resistance, and miscarriage, focusing on inflammatory response and endometrial receptivity. MethodsThirty female SPF-grade SD rats with regular estrous cycles and in proestrus, and 15 male SPF-grade SD rats were housed together in a 2∶1 ratio at 18:00. At 8:00 next morning, rats showing abundant sperm and vaginal plugs were considered pregnant on the day 0.5. The 30 pregnant rats were randomly divided into three groups, normal group, model group, and MSP group, with 10 rats in each group. From day 0.5 to day 13.5 of pregnancy, the MSP group was given 26.6 g/(kg·d) of the MSP via gavage twice a day for 14 consecutive days. The normal group and the model group received 4 ml of normal saline daily. From day 7.5 to day 13.5 of pregnancy, the rats in the model group and MSP group were intraperitoneally injected with dihydrotestosterone (DHT) and insulin (INS) for 7 consecutive days to establish a PCOS model with hyperandrogenism, insulin resistance, and miscarriage. On day 13.5 of pregnancy, an oral glucose tolerance test (OGTT) was performed to measure blood glucose levels at 0, 30, 60, 90, and 120 minutes. On day 14.5, serum level of progesterone (P4), estradiol (E2), fasting insulin (FINS), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured by ELISA. The insulin resistance index (HOMA-IR) was calculated. Embryo implantation, miscarriage rate, and average number of live fetuses were observed. Uterine tissue pathology was examined by HE staining, and mRNA expression of Il-6, Tnf-α, leukemia inhibitory factor (Lif), homeobox gene 10 (Hoxa10), prolactin family 8 subfamily A member 2 (Prl8a2), and insulin-like growth factor-binding protein 1 (Igfbp1) in the uterine tissue was detected by qRT-PCR. ResultsCompared with the normal group, the model group had significantly higher blood glucose level at 0, 30, 60, 90, and 120 minutes, increased miscarriage rate, elevated HOMA-IR, decreased average number of live fetuses, lower level of P4 and E2, higher level of IL-6, TNF-α, and FINS, and higher mRNA expression of Il-6 and Tnf-α in the uterine tissue. The mRNA expression of Lif, Hoxa10, and Prl8a2 was reduced (P<0.05 or P<0.01). The uterus had a dark red color, visible areas of bleeding, fewer embryos with developmental abnormalities, and increased placental necrosis. Pathological examination revealed thrombus in the decidual layer, unclear decidual cell morphology, loose arrangement, scattered distribution, edema degeneration in the cytoplasm, and nuclear shrinkage or disappearance, with extensive infiltration of inflammatory cells. In contrast, compared with the model group, the MSP group showed significantly lower blood glucose level at 0, 30, 60, 90, and 120 min, reduced miscarriage rate, lower HOMA-IR, increased number of live fetuses, higher level of P4 and E2, and lower level of IL-6, TNF-α, and FINS. The mRNA expression of Il-6 and Tnf-α in the uterine tissue was lower, while the expression of Lif, Hoxa10, and Prl8a2 mRNA was higher (P<0.05 or P<0.01). There was significant improvement in uterine and embryo conditions, as well as in uterine tissue pathology. ConclusionThe MSP can reduce the miscarriage rate in a PCOS model with hyperandrogenism, insulin resistance, and miscarriage. Its mechanism may involve inhibiting inflammation, improving endometrial receptivity, and restoring the defects in endometrial decidualization.
2.Clinical trial of brexpiprazole in the treatment of adults with acute schizophrenia
Shu-Zhe ZHOU ; Liang LI ; Dong YANG ; Jin-Guo ZHAI ; Tao JIANG ; Yu-Zhong SHI ; Bin WU ; Xiang-Ping WU ; Ke-Qing LI ; Tie-Bang LIU ; Jie LI ; Shi-You TANG ; Li-Li WANG ; Xue-Yi WANG ; Yun-Long TAN ; Qi LIU ; Uki MOTOMICHI ; Ming-Ji XIAN ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):654-658
Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50%(140 cases/184 cases)and 82.40%(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P>0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P>0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P>0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00%vs.64.50%,P>0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.
3.Content determination of seventeen amino acids in Gualoupi Injection and its intermediates and research on their change laws
Xiang TAO ; Jing-Xian ZHANG ; Qing HU ; Jian SUN ; Ying DONG ; Jin-Guo DING ; Hong YU ; Ying-Ying SHEN ; Xiu-Hong MAO ; Shen JI
Chinese Traditional Patent Medicine 2024;46(3):709-717
AIM To determine the contents of aspartic acid,glutamic acid,serine,glycine,threonine,citrulline,arginine,alanine,γ-amino-butyric acid,tyrosine,valine,phenlalanine,isoleucine,ornithine,leucine,lysine and proline in Gualoupi Injection and its intermediates,and to analyze their change laws.METHODS The OPA-FMOC online derivatization analysis was performed on a 45℃ thermostatic Waters XBridge C18 column(4.6 mm×100 mm,3.5 μm),with the mobile phase comprising of phosphate buffer solution-[methanol-acetonitrile-water(45 : 45 : 10)]flowing at 1 mL/min in a gradient elution manner,and the detection wavelengths were set at 262,338 nm.Principal component analysis and heatmap analysis were adopted in chemical pattern recognition for the corresponding intermediates in ten processes of six batches of samples.RESULTS Seventeen amino acids showed good linear relationships within their own ranges(R2>0.998 0),whose average recoveries were 83.4%-119.5%with the RSDs of 0.91%-7.94%.Different batches of samples in the same process were clustered,and the corresponding intermediates in different processed were clustered into three groups.Alcohol precipitation and cation exchange column demonstrated the biggest influences on amino acid composition.CONCLUSION This experiment can provide important references for the critical factors on quality control of Gualoupi Injection,thus ensure the stability and uniformity of final product.
4.Design of portable collection device for exhaled breath condensate
An XIANG ; Lei ZHOU ; Qi-Feng JI ; Yuan-Zhe LI ; Qin WANG ; Shi-Man ZHU ; Jie PENG ; Xiao-Ying LEI ; Wei-Na LI ; Li WANG ; Yan-Hai GUO ; Zi-Fan LU
Chinese Medical Equipment Journal 2024;45(8):32-37
Objective To develop a portable collection device of human exhaled breath condensate(EBC)based on natural breathing to meet the needs for rapid screening of human respiratory tract(especially lower respiratory tract)infections.Methods The device consisted of a refrigeration unit,a heat dissipation unit and a condensation unit.The refrigeration unit adopted a TES1-7102 thermoelectric Peltier cooler semiconductor as the refrigeration element;the heat dissipation unit was composed of a high thermal conductivity aluminum heat sink and a high-speed brushless cooling fan;the condensation unit was made up of a cold guide plate and a condenser,in which the cold guide plate was made of thin sheet of aluminum alloy,and the condenser was prepared by 3D printing technology and made of hydrophobic polylactic acid,with primary and secondary 2-stage guide grooves and an ultra-thin condensing surface.The performance of the device was verified in terms of cooling,thermal conductivity,condensation and human EBC collection and content analysis.Results Performance analysis showed that after refrigeration began the temperature difference between the condenser surface and the exhaled gas met the requirements of the condenser,and no obvious thermal resistance was found on the condensing surface so that large droplets could be formed rapidly and then be collected after the gas-liquid phase change of the exhaled gas on the condensing surface.Human EBC collection and content analysis indicated the device realized home self-collection of EBCs from people of all ages,and the concentrations of interleukins,C-reactive protein and other inflammation-related indexes and the pH value of the collected EBC samples were all correlated with respiratory infections in the subjects.Conclusion The device developed with easy operation avoids the discomfort of blowing collection and the risk of saliva contamination,and is worthy promoting for rapid diagnosis and dynamic monitoring of respiratory tract infection and other related diseases.[Chinese Medical Equipment Journal,2024,45(8):32-37]
5.ZHOU Peng's Experience in Treating Psoriasis Vulgaris of Blood Stasis Type Based on the Analysis of Dermoscopic Signs
Guo-Ao SHI ; Rui-Ming CHEN ; Xiang JI ; Zhong-Xian LI ; Yong-Qin XIONG ; Xia-Yun ZHOU ; Jing-Jing LI ; Peng ZHOU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(8):2109-2115
Professor ZHOU Peng has deeply discussed the pathological characteristics of psoriasis vulgaris,emphasizing that the disease is usually manifested deficiency interweaved with excess,leading to frequent recurrence and persistent refractory,which may lead to psychological and emotional problems of patients.This paper further expounds the effect of blood stasis on the pathogenesis,progression and prognosis of psoriasis,and puts forward a new method of combining Lingnan fire needling and filiform needling acupuncture technique to treat psoriasis vulgaris with blood stasis syndrome.Professor ZHOU Peng believes that the treatment principle of this disease is"regulating the mind first,rectifying blood as a base,syndrome differentiating and eliminating pathogenic factors",aiming at comprehensively considering the etiology and symptoms,in order to achieve more effective treatment results.Combined with the analysis of dermoscopic signs,it provides a possible improvement direction for the treatment of psoriasis vulgaris from a new perspective.
6.Effect of CD8+CD28-T Cells on Acute Graft-Versus-Host Disease after Haploidentical Hematopoietic Stem Cell Transplantation
An-Di ZHANG ; Xiao-Xuan WEI ; Jia-Yuan GUO ; Xiang-Shu JIN ; Lin-Lin ZHANG ; Fei LI ; ZHEN-Yang GU ; Jian BO ; Li-Ping DOU ; Dai-Hong LIU ; Meng LI ; Chun-Ji GAO
Journal of Experimental Hematology 2024;32(3):896-905
Objective:To investigate the effect of CD8+CD28-T cells on acute graft-versus-host disease(aGVHD)after haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods:The relationship between absolute count of CD8+CD28-T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT,and the differences in the incidence rate of chronic graft-versus host disease(cGVHD),infection and prognosis between different CD8+CD28-T absolute cells count groups were compared.Results:aGVHD occurred in 40 of 60 patients after haplo-HSCT,with an incidence rate of 66.67%.The median occurrence time of aGVHD was 32.5(20-100)days.At 30 days after the transplantation,the absolute count of CD8+CD28-T cells of aGVHD group was significantly lower than that of non-aGVHD group(P=0.03).Thus the absolute count of CD8+CD28-T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent.At 30 days after transplantation,the incidence rate of aGVHD in the low cell count group(CD8+CD28-T cells absolute count<0.06/μl)was significantly higher than that in the high cell count group(CD8+CD28-T cells absolute count ≥0.06/μl,P=0.011).Multivariate Cox regression analysis further confirmed that the absolute count of CD8+CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD,and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group(P=0.015).The incidence of cGVHD,fungal infection,EBV infection and CMV infection were not significantly different between the two groups with different CD8+CD28-T cells absolute count.The overall survival,non-recurrent mortality and relapse rates were not significantly different between different CD8+CD28-T cells absolute count groups.Conclusion:Patients with delayed CD8+CD28-T cells reconstitution after haplo-HSCT are more likely to develop aGVHD,and the absolute count of CD8+CD28-T cells can be used to predict the incidence of aGVHD to some extent.The absolute count of CD8+CD28-T cells after haplo-HSCT was not associated with cGVHD,fungal infection,EBV infection,and CMV infection,and was also not significantly associated with the prognosis after transplantation.
7.Clinical features of TFE3-rearranged renal cell carcinoma
Shuoming ZHOU ; Wenliang MA ; Xiang DONG ; Guangxiang LIU ; Changwei JI ; Gutian ZHANG ; Weidong GAN ; Hongqian GUO
Chinese Journal of Urology 2023;44(6):427-433
Objective:A single-center analysis was performed to assess the significant clinical features and prognostic factors of TFE3-rearranged renal cell carcinoma (TFE3 rRCC).Methods:The clinical data of 85 confirmed cases of TFE3 rRCC patients at the Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2007 to February 2023 were analyzed retrospectively. Among these patients, there were 39 males and 46 females, with a median age of 32 (26, 45) years. All patients underwent preoperative CT scans, 21/85 cases (24.7%) of TFE3 rRCC exhibited the characteristic feature of "circular calcification" with plain CT imaging, and enhanced CT scan showed that the tumor enhancement during the arterial phase was lower than the adjacent renal cortex. Among the 85 patients in this cohort, the median tumor diameter was 4.8(3.2, 6.5). Thirty-two patients underwent partial nephrectomy (NSS), while 51 patients underwent radical nephrectomy (RN). Two patients with distant metastasis at the time of diagnosis received only sunitinib therapy. Forty-three patients received adjuvant treatment, including 14 patients who received targeted therapy. There were 29 patients in AJCC stage Ⅲ/Ⅳ, with 10 patients presenting with venous tumor thrombus and 14 patients with lymph node metastasis. Histopathology, TFE3 immunohistochemistry, and break-apart TFE3 FISH probe detection were performed on all 85 cases, while 52 patients underwent RT-PCR and/or DNA sequencing. By combining the clinical and pathological data, we summarized the diagnostic Methods for TFE3 rRCC, evaluated the impact of surgical approaches (RN and NSS) on the survival outcomes of cT 1a/b patients, and assessed the influence of genetic subtypes (ASPL, NONO, PRCC, SFPQ, and others) on the survival outcomes of all patients. Furthermore, we analyzed the risk factors for disease progression. Results:TFE3 rRCC exhibited variable histopathological features, and the presence of acinar-like structures with psammoma bodies may be a relatively typical characteristic. All 85 patients showed positive TFE3 immunohistochemical staining. In 6 cases of TFE3 rRCC, break-apart TFE3 FISH probe yielded negative results. However, final confirmation was achieved through genetic sequence, with 5 cases diagnosed as NONO-TFE3 subtype and 1 case as RBM10-TFE3 subtype. Among the 85 patients, 52 underwent RT-PCR and/or DNA sequencing, revealing a total of 8 TFE3 fusion subtypes, including 11 cases of ASPL-TFE3, 8 cases of PRCC-TFE3, 10 cases of NONO-TFE3, 15 cases of SFPQ-TFE3, 1 case of CLTC-TFE3, 2 cases of LUC7L3-TFE3, 4 cases of MED15-TFE3, and 1 case of RBM10-TFE3. The survival analysis results revealed that among the 12 patients with cT 1b stage tumors who underwent radical nephrectomy (RN), the progression-free survival (PFS) was 35 (14, 109) months, which was significantly better than the NSS group ( P=0.041). However, for the 14 patients with cT 1a stage tumors who underwent RN, there was no statistically significant difference in overall survival (OS) and PFS compared to the NSS group, with OS being 55(27, 134) months and PFS being 71(41, 134) months. Stratifying according to TFE3 fusion subtypes, it was found that patients with ASPL-TFE3 fusion had a significantly lower PFS compared to those with non-ASPL-TFE3 fusion subtypes ( P=0.029). Survival analysis revealed that tumor diameter, surgical approach, adjuvant therapy, AJCC staging, venous tumor thrombus, and lymph node metastasis were associated with OS and PFS( P<0.05). The results of the multivariate Cox regression analysis showed that AJCC stage Ⅲ/Ⅳ( HR=2.393, 95% CI 1.418-4.039, P=0.001) and venous tumor thrombus ( HR=3.543, 95% CI 1.159-10.827, P=0.026) were independent risk factors for progression-free survival (PFS). Conclusions:During the non-enhanced phase of CT scan, TFE3 rRCC tumors can exhibit a circular calcification. TFE3 immunohistochemistry is an important screening method for TFE3 rRCC.Break-apart TFE3 FISH probe detection is considered the diagnostic gold standard, and gene sequencing, if feasible, can provide the subtype diagnosis of TFE3 rRCC. For cT 1a stage TFE3 rRCC, partial nephrectomy (NSS) is a viable option, while caution should be taken in selecting NSS for cT1b stage patients. Patients with ASPL-TFE3 fusion subtype have a worse prognosis. AJCC stage Ⅲ/Ⅳ and venous tumor thrombus indicate poor prognosis in TFE3 rRCC.
8.Acupuncture for prevention of moderate to severe seasonal allergic rhinitis: a randomized controlled trial.
Ting-Ting SONG ; Xiang-Hong JING ; Wei GUO ; Guan-Xiong HAN ; Shuo DU ; Ji-Ping ZHAO
Chinese Acupuncture & Moxibustion 2023;43(2):123-127
OBJECTIVE:
To observe the clinical efficacy of acupuncture for prevention of moderate to severe seasonal allergic rhinitis.
METHODS:
A total of 105 patients with moderate to severe seasonal allergic rhinitis were randomly divided into an observation group (53 cases, 3 cases dropped off) and a control group (52 cases, 4 cases dropped off). The patients in the observation group were treated with acupuncture at Yintang (GV 24+), Yingxiang (LI 20), Hegu (LI 4), Zusanli (ST 36), Fengchi (GB 20), Feishu (BL 13), etc. 4 weeks before the seizure period, once every other day, 3 times a week for 4 weeks. The patients in the control group were not given any intervention before the seizure period. Emergency drugs can be given appropriately during the seizure period in both groups. After seizure period, the seizure rate was recorded in the two groups; before treatment and on week 1, 2, 4, 6 of seizure period after treatment, the rhinoconjunctivitis quality of life questionnaire (RQLQ) score and total nasal symptom score (TNSS) were observed in the two groups; the rescue medication score (RMS) was recorded on week 1-6 of seizure period in the two groups.
RESULTS:
The seizure rate of the observation group was 84.0% (42/50), which was lower than 100.0% (48/48) in the control group (P<0.05). After treatment, the scores of RQLQ and TNSS at each time point of seizure period were decreased compared with before treatment in the observation group (P<0.01), which were lower than the control group (P<0.01). The RMS score at each time point of seizure period in the observation group was lower than the control group (P<0.05, P<0.01).
CONCLUSION
Acupuncture can reduce the incidence of moderate to severe seasonal allergic rhinitis, relieve the symptoms, improve the quality of life and reduce the use of emergency drugs.
Humans
;
Rhinitis, Allergic, Seasonal
;
Rhinitis, Allergic/therapy*
;
Quality of Life
;
Acupuncture Therapy
;
Acupuncture Points
;
Treatment Outcome
;
Seizures
9.Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial.
Lu-da YAN ; Zhong-Xian LI ; Yu ZHANG ; Xue-Song LIANG ; Jing-Jing LI ; Miao WU ; Guo-Ao SHI ; Rui-Ming CHEN ; Xiang JI ; Si-Yao ZUO ; Shi-Yun CHEN ; Peng ZHOU ; Wen-Bin FU
Chinese Acupuncture & Moxibustion 2023;43(3):255-260
OBJECTIVE:
To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability.
METHODS:
Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups.
RESULTS:
After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05).
CONCLUSION
Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.
Humans
;
Depression
;
Quarantine
;
Serotonin
;
Sleep Initiation and Maintenance Disorders
;
COVID-19
;
Acupuncture Therapy
;
Comorbidity
10.Gene mutation profiles and clinicopathological features of patients with non-small cell lung cancer harboring KRAS G12C mutation: a single-center retrospective study.
Lian Ying GUO ; Chan XIANG ; Rui Ying ZHAO ; Sheng Nan CHEN ; Sheng Ji MA ; Yu Chen HAN
Chinese Journal of Pathology 2023;52(2):117-123
Objective: To accurately screen non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation and to evaluate their clinicopathological features, prognostic factors and current treatment status. Methods: A total of 19 410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital, Shanghai, China from January 2018 to September 2021 were retrospectively reviewed, and the cases with KRAS gene mutation detected by next-generation sequencing were included. The clinicopathological and genetic mutation data of these cases were collected and analyzed. Results: A total of 1 633 (8.4%) NSCLC patients carried a KRAS gene mutation, among whom G12C was the most frequent (468 cases, 28.7%) mutant subtype. The mutation was more commonly found in males (414/468, 88.5%), patients with a history of smoking (308/468, 65.8%), and patients with a pathological type of invasive adenocarcinoma (231/468, 49.4%). The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53 (52.4%, 245/468), STK11 (18.6%, 87/468) and ATM (13.2%, 62/468). The proportion of PD-L1 expression (≥1%) in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation [64.3% (90/140) vs. 56.1% (193/344), P=0.014]. Immune checkpoint inhibitors (ICIs) treatment significantly prolonged progression-free survival (PFS) in NSCLC patients (10.0 months vs. 5.0 months, P=0.011). However, combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC (P>0.05). Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation (9.0 months vs. 4.3 months, P=0.012). Conclusions: Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment. The feasibility of chemotherapy, ICIs therapy and their combination needs further investigation.
Humans
;
Male
;
B7-H1 Antigen/genetics*
;
Carcinoma, Non-Small-Cell Lung/pathology*
;
China
;
Lung Neoplasms/pathology*
;
Mutation
;
Proto-Oncogene Proteins p21(ras)/genetics*
;
Retrospective Studies
;
Female

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