Objective To investigate the expression of HSPA9 in hepatocellular carcinoma(HCC) and its relationship with clinicopathological features and prognosis.Methods Forty-nine cases HCC treated by operative resection and follow up data in our hospital from January 2006 to January 2010 were retrospectively analyzed.Immunohistochemistry was performed to determine the expression of HSPA9 in HCC and paratumor tissues.The relationship between HSPA9 expression and clinicopathological features and prognosis was statistically analyzed.Results The HSPA9 protein expression in tumor tissue was higher that that in the paratumor tissue(t=6.601,P＜0.01),moreover the over expression of HSPA9 was significantly correlated with lymph node metastasis (P =0.005),TNM-stage(P =0.015),tumor differentiation (P =0.033),microvascular invasion (P =0.009) and recurrence (P =0.047).In the survival analysis results,the patients with over expression of HSPA9 had a much lower total survival rate(P=0.002)and much higher postoperative cumulative recurrence rate(P =0.003).There were significant differences in TNM-stage,microvascular invasion,lymph node metastasis,tumor differentiation and HSPA9 staining for overall survival and cumulative recurrence rate based on a univariate analysis(P＜0.05).Conclusion HSPA9 has over expression in HCC.The over expression of HS-PA9 is closely related to invasion and metastasis pathological features and can serve as an independent prognostic risk factor for predicting the prognosis of HCC.

ObjectiveTo investigate the prevalence,antibiotic characteristics as well as molecular background of community-associated methicillin-sensitive Staphylococcus aureus (CA-MRSA) from patients with skin and sofi tissue infections from 4 different hospitals in Beijing.MethodsFive hundred and one patients were enrolled from 4 hospitals prospectively.Patients with skin and soft tissue infections and no risk factors for healthcare-associated acquisition were included.Sample from the infection sites were collected for culture.Case report form was filled out for each patient.Antibiotic susceptibility test and molecular analysis was performed for each Staphylococcus aureus isolate.ResultsTotally 164 Staphylococcus aureus isolates were cultured from the patients with skin and soft tissue infections.Of them 5 isolates were CA-MRSA.These 5 CA-MRSA isolates harbored SCCmec Ⅰ, SCCmec Ⅲ, SCCmec Ⅳ,SCCmec Ⅴ and untypable,respectively.CA-MRSA was highly resistant to β-lactamase,levofloxacin,erythromycin and clindamycin,but susceptible to vancomycin,teicoplanin,linezolid,daptomycin,and trimethoprim/sulfamethoxazole.Prevalence of PVL in community-associated methicillin sensitive Staphylococcus aureus(CA-MSSA) and CA-MRSA were 41.9％ and 2/5.Other toxins expressed similarly between them.Combined with multilocus sequence typing (MLST) and spa typing,the major clones of CA-MSSA were ST398-t034,ST7-t796,ST398-t571,ST1t127,and ST188-t189,while in CA-MRSA were ST239-t037-SCCmec Ⅰ,ST239-t632-SCCmecⅢ,ST59-t437-SCCmecV,ST8-t008-SCCmecⅣ,and ST6-t701-NT.ConclusionsThe low prevalence of CA-MRSA in Beijing and complexity of the genetic background in CA-MRSA were observed.Clone spread is not found among CA-MRSAisolates.CA-MRSAexhibithigher resistancecomparedwithmethicillinsensitive Staphylococcus aureus (MSSA).Rational drug use scheme is called in the clinical practice to prevent development of high level resistance.

OBJECTIVETo investigate the feasibility and efficacy of clockwise modularized lymphadenectomy in laparoscopic gastrectomy for gastric cancer.

METHODSClinical data of 19 cases who underwent the laparoscopic clockwise modularized lymphadenectomy for gastric cancer (clockwise group) from July 2016 to September 2016 were analyzed retrospectively. The clockwise modularized lymphadenectomy included the fixed operative order, detailed procedure and requirement of lymphadenectomy, which mainly reflected in assisting the exposure of operative field and dissection of lymph nodes through suspending the liver and banding the greater omentum, as well as proposing the requirements and attentions for the dissections of each station of lymph nodes to facilitate the quality control of lymphadenectomy. The operative time, intraoperative complications, intraoperative estimate blood loss, number of total harvested lymph nodes, morbidity and postoperative recovery, were compared with the data of another 19 cases who received traditional lymphadenectomy from January 2016 to June 2016 (control group).

RESULTSThe baseline data were comparable between two groups. All the patients were performed successfully by laparoscopy without conversion and intraoperative complications. The operative time, intraoperative estimated blood loss and number of total harvested lymph node were (278.4±29.9) min, (91.1±41.6) ml and 38.2±15.1 in clockwise group, and were (296.7±30.3) min, (102.2±32.2) ml and 37.0±12.3 in control group without significant differences (all P>0.05). However, the mean number of retrieved No.11p lymph nodes was 2.2±1.8 in clockwise group, which was significantly higher than that in control group (0.8±1.0) (P=0.013). Four patients in each group suffered from pulmonary infections, who were cured by conservative therapies. There was no anastomotic leakage, intraperitoneal hemorrhage, intraperitoneal infection or intestinal obstruction in each group.

CONCLUSIONThe clockwise modularized lymphadenectomy can contribute to the facilitation of the retraction and exposure, decrease of the surgical duration and intraoperative blood loss, and radicalization of lymph node dissection, especially for the lymph nodes dissection around the celiac trunk.

Blood Loss, Surgical ; prevention & control ; statistics & numerical data ; Convalescence ; Gastrectomy ; methods ; Humans ; Intraoperative Complications ; epidemiology ; Laparoscopy ; methods ; Lymph Node Excision ; methods ; statistics & numerical data ; Lymph Nodes ; surgery ; Operative Time ; Retrospective Studies ; Stomach Neoplasms ; surgery ; Treatment Outcome

Gastric cancer （GC）， originating from gastric mucosal epithelium， threatens the life and health of patients. The morbidity and mortality are high in developing countries including China. Despite the major headway in medical technology， methods such as surgery， chemotherapy， and targeted therapy fail to curb the progression. Thus， it is particularly important to clarify the etiopathogenesis and molecular mechanism of this disease and develop effective therapy. The continuous progression of GC is inseparable from the changes in the energy metabolism of tumor cells. Aerobic glycolysis （AEG）， as a unique metabolic method of tumors， directly or indirectly results in various malignant phenotypes of GC tissues. The tumor microenvironment promotes the AEG， as its disordered signaling molecules activate a large number of signaling pathways， key proteins， glycolysis-related enzymes， and various genes that initiate AEG and regulate its activity and ultimately improve the AEG level. In recent years， major progress has been made in research on the intervention of AEG in GC cells with Chinese medicinals， components of Chinese medicinals， and compound Chinese medicine prescriptions. Chinese medicine has shown multi-target and multi-pathway characteristics in the anti-GC process， thus attracting the interest of scholars in China and abroad. This study reviews the intervention of Chinese medicine in AEG of GC from the aspects of genes， proteins， key enzymes of glycolysis， and signaling pathways， in order to further clarify the exact role of AEG in the development of GC and the specific relationship of Chinese medicine with AEG and GC. In addition， the limitations of available research were summarized. This study is expected to provide a reference for future clinical and experimental research in related fields.

ObjectiveTo investigate the effect of Qi-invigorating and blood-activating therapy on the miR216b/Beclin1 pathway in mice with atrophic precancerous lesions of gastric cancer （PLGC） and analyze its mechanism in autophagy of PLGC. MethodSeventy-five healthy male SPF KM mice were randomly divided into a blank group and a model group. Mice in the model group were given 1-methyl-3-nitroso-1-nitrosoguanidine （MNNG） solution （150 mg·L^-1） for free drinking and gavage and ranitidine solution （0.03 g·kg^-1） daily for 12 weeks. According to the random control table， mice were divided into a model group， a Qi-invigorating group （3.5 g·kg^-1 of Astragali Radix）， a blood-activating group （0.7 g·kg^-1 of Notoginseng Radix et Rhizoma powder）， a Qi-invigorating and blood-activating group （3.5 g·kg^-1 of Astragali Radix + 0.7 g·kg^-1 of Notoginseng Radix et Rhizoma powder）， and a folic acid group （2 mg·kg^-1）. The corresponding drugs were given to mice in each group for 8 weeks and then the tissues were collected. Hematoxylin-eosin （HE） staining was carried out to observe the changes in gastric mucosa. Western blot was used to detect the protein expression of microtuble-associated protein 1 light chain 3 （LC3）Ⅰ， LC3Ⅱ， and Beclin1. Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Beclin1 and miR-216b. ResultPathological observation showed that as compared with the blank group， the intrinsic glands of gastric mucosa decreased with atrophy and intestinal metaplasia in the model group， which were improved in all treatment groups， and the improvement of the Qi-invigorating and blood-activating group was the most obvious. As compared with the blank group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of the model group was significantly decreased （P<0.05）. As compared with the model group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of each treatment group was increased （P<0.05， P<0.01）. The increase was most obvious in the Qi-invigorating and blood-activating group. As compared with the blank group， the mRNA expression of Beclin1 in the model group was decreased （P<0.05）， and that of miR216b was increased （P<0.05）. As compared with the model group， the mRNA expression of Beclin1 was increased and that of miR216b was decreased in each treatment group （P<0.05）， and the changes were the most obvious in the Qi-invigorating and blood-activating group. ConclusionThe mechanism of the Qi-invigorating and blood-activating therapy， represented by Astragali Radix and Notoginseng Radix et Rhizoma， in treating PLGC may be through inhibiting the expression of miR216b and activating Beclin1， thus promoting autophagy and repairing gastric mucosa.

Objective:To analyze the safety of paclitaxel-based, hyperthermic, intraperitoneal perfusion chemotherapy (HIPEC) after radical resection of locally advanced gastric cancer.Methods:This was a retrospective cohort study of clinicopathological data of 467 patients with locally advanced gastric adenocarcinoma who had been admitted to the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between July 2019 and April 2021. Among these patients, 151 had undergone radical resection combined with post-operative paclitaxel-based HIPEC (surgery+HIPEC group) and 316 radical resection alone (surgery group). The adverse perioperative events in study patients were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) published by the U.S. Department of Health and Human Services. Subgroup analysis was performed on patients in the surgery+HIPEC group according to the number of times HIPEC was administered and the incidence of adverse events was compared between subgroups using the χ 2 test. Independent risk factors for paclitaxel-based HIPEC-associated adverse events were identified by applying a logistic model. Results:In the surgery+HIPEC group, there were 113 (74.8%) male and 38 (25.2%) female patients of median age 64 (55, 68) years, 18 (11.9%), 79 (52.3%), and 54 (35.8%) of whom had undergone one, two, and three paclitaxel-based HIPEC treatments, respectively, after surgery. The median maximum tumor diameter was 5.0 (3.6, 6.5) cm. In the surgery group, there were 244 (77.2%) male and 72 (22.8%) female patients of median age 63 (54, 68) and the median maximum tumor diameter was 4.0 (3.0, 5.5) cm. In the surgery+HIPEC group, 112 patients (74.2%) had 198 Grade 2 or higher adverse perioperative events, postoperative hypoalbuminemia being the commonest (85 cases, 56.3%), followed by postoperative anemia (50 cases, 33.1%). Compared with the surgery group, the incidences of postoperative hypoalbuminemia (56.3% [85/151] vs. 37.7% [119/316], χ 2=14.420, P<0.001), anemia (33.1% [50/151] vs. 22.5% [71/316], χ 2=6.030, P=0.014), abdominal pain [7.3% [11/151] vs. 1.6% [5/316], χ 2=10.042, P=0.002) and abdominal distension (5.3% [8/151] vs. 1.3% [4/316], χ 2=5.123, P=0.024) were all significantly higher in the surgery+HIPEC group. Analysis of the three HIPEC subgroups revealed significant differences in the incidences of postoperative hypoalbuminemia (13/18 vs. 67.1% [53/79] vs. 35.2% [19/54], χ 2=12.955, P<0.001) and pulmonary infection (6/18 vs. 6.3% [5/79] vs. 1.9% [1/54], χ 2=13.232, P<0.001) between them. Univariate analysis identified body mass index, Borrmann's type and number of HIPEC treatments as associated with perioperative adverse events in the surgery+HIPEC group ( P<0.05). However, according to multifactorial logistic analysis, the above factors were not independent risk factors for perioperative adverse events in the surgery+HIPEC group ( P>0.05). Conclusions:Paclitaxel-based HIPEC after radical resection significantly increases the risk of postoperative hypoalbuminemia, anemia, abdominal pain, and abdominal distension in patients who have undergone excision of locally advanced gastric cancer. However, increasing the frequency of HIPEC treatments did not significantly increase the risk of paclitaxel-based HIPEC-related adverse events. Moreover, univariate and multivariate analysis did not identify any independent risk factors for paclitaxel HIPEC-related adverse events.

Objective:To explore the effect of standardized surgical treatment and multidisciplinary treatment strategy on the treatment outcomes of gastric cancer patients.Methods:A single-center cohort study was carried out. Clinicopathological and long-term follow up data of primary gastric cancer patients were retrieved from the database of Surgical Gastric Cancer Patient Registry (SGCPR) in West China Hospital of Sichuan University. Finally, 4516 gastric cancer patients were included and were divided into three groups according to time periods (period 1 group: exploration stage of standardized surgical treatment, 2000 to 2006, 967 cases; period 2 group: application stage of standardized surgical treatment, 2007 to 2012, 1962 cases; period 3 group: optimization stage of standardized surgical treatment and application stage of multidisciplinary treatment strategy, 2013 to 2016, 1587 cases). Differences in clinical data, pathologic features, and prognosis were compared among 3 period groups. Follow-up information was updated to January 1, 2020. The overall follow-up rate was 88.9% (4016/4516) and median follow-up duration was 51.58 months. Survival curve was drawn by Kaplan-Meire method and compared with log-rank test. Univariate and multivariate analyses were performed by Cox proportional hazards model.Results:There were significant differences among period 1, period 2 and period 3 groups in the rates of D2/D2+ lymphadenectomy [14.4%(139/967) vs. 47.2%(927/1962) vs. 75.4%(1197/1587), χ 2=907.210, P<0.001], in the ratio of proximal gastrectomy [19.8%(191/967) vs. 16.6%(325/1962) vs. 8.2%(130/1587), χ 2=100.020, P<0.001], and in the median intraoperative blood loss (300 ml vs. 100 ml vs. 100 ml, H=1126.500, P<0.001). Besides, the increasing trend and significant difference were also observed in the median number of examined lymph nodes among period 1, period 2 and period 3 groups (14 vs. 26 vs. 30, H=987.100, P<0.001). Survival analysis showed that the 5-year overall survival rate was 55.3% in period 1, 55.2% in period 2 and 62.8% in period 3, and significant difference existed between period 3 and period 1 ( P=0.004). The Cox proportional hazards model analysis showed that treatment period (period 3, HR=0.820, 95%CI: 0.708 to 0.950, P=0.008), postoperative chemotherapy (HR=0.696, 95%CI: 0.631 to 0.768, P<0.001) and mid-low gastric cancer (HR=0.884, 95%CI: 0.804 to 0.973, P=0.011) were good prognostic factors. Whereas old age (≥65 years, HR=1.189, 95%CI: 1.084 to 1.303, P<0.001), palliative resection (R1/R2, HR=1.538,95%CI: 1.333 to 1.776, P<0.001), large tumor size (≥5 cm, HR=1.377, 95%CI: 1.239 to 1.529, P<0.001), macroscopic type III to IV (HR=1.165, 95%CI: 1.063 to 1.277, P<0.001) and TNM stage II to IV(II/I: HR=1.801,95% CI:1.500~2.162, P<0.001;III/I: HR=3.588, 95% CI: 3.028~4.251, P<0.001; IV/I: HR=6.114, 95% CI: 4.973~7.516, P<0.001) were independent prognostic risk factors. Conclusion:Through the implementation of standardized surgical treatment technology and multidisciplinary treatment model, the quality of surgery treatment and overall survival increase, and prognosis of gastric cancer patients has been improved.

Objective:To explore the effect of standardized surgical treatment and multidisciplinary treatment strategy on the treatment outcomes of gastric cancer patients.Methods:A single-center cohort study was carried out. Clinicopathological and long-term follow up data of primary gastric cancer patients were retrieved from the database of Surgical Gastric Cancer Patient Registry (SGCPR) in West China Hospital of Sichuan University. Finally, 4516 gastric cancer patients were included and were divided into three groups according to time periods (period 1 group: exploration stage of standardized surgical treatment, 2000 to 2006, 967 cases; period 2 group: application stage of standardized surgical treatment, 2007 to 2012, 1962 cases; period 3 group: optimization stage of standardized surgical treatment and application stage of multidisciplinary treatment strategy, 2013 to 2016, 1587 cases). Differences in clinical data, pathologic features, and prognosis were compared among 3 period groups. Follow-up information was updated to January 1, 2020. The overall follow-up rate was 88.9% (4016/4516) and median follow-up duration was 51.58 months. Survival curve was drawn by Kaplan-Meire method and compared with log-rank test. Univariate and multivariate analyses were performed by Cox proportional hazards model.Results:There were significant differences among period 1, period 2 and period 3 groups in the rates of D2/D2+ lymphadenectomy [14.4%(139/967) vs. 47.2%(927/1962) vs. 75.4%(1197/1587), χ 2=907.210, P<0.001], in the ratio of proximal gastrectomy [19.8%(191/967) vs. 16.6%(325/1962) vs. 8.2%(130/1587), χ 2=100.020, P<0.001], and in the median intraoperative blood loss (300 ml vs. 100 ml vs. 100 ml, H=1126.500, P<0.001). Besides, the increasing trend and significant difference were also observed in the median number of examined lymph nodes among period 1, period 2 and period 3 groups (14 vs. 26 vs. 30, H=987.100, P<0.001). Survival analysis showed that the 5-year overall survival rate was 55.3% in period 1, 55.2% in period 2 and 62.8% in period 3, and significant difference existed between period 3 and period 1 ( P=0.004). The Cox proportional hazards model analysis showed that treatment period (period 3, HR=0.820, 95%CI: 0.708 to 0.950, P=0.008), postoperative chemotherapy (HR=0.696, 95%CI: 0.631 to 0.768, P<0.001) and mid-low gastric cancer (HR=0.884, 95%CI: 0.804 to 0.973, P=0.011) were good prognostic factors. Whereas old age (≥65 years, HR=1.189, 95%CI: 1.084 to 1.303, P<0.001), palliative resection (R1/R2, HR=1.538,95%CI: 1.333 to 1.776, P<0.001), large tumor size (≥5 cm, HR=1.377, 95%CI: 1.239 to 1.529, P<0.001), macroscopic type III to IV (HR=1.165, 95%CI: 1.063 to 1.277, P<0.001) and TNM stage II to IV(II/I: HR=1.801,95% CI:1.500~2.162, P<0.001;III/I: HR=3.588, 95% CI: 3.028~4.251, P<0.001; IV/I: HR=6.114, 95% CI: 4.973~7.516, P<0.001) were independent prognostic risk factors. Conclusion:Through the implementation of standardized surgical treatment technology and multidisciplinary treatment model, the quality of surgery treatment and overall survival increase, and prognosis of gastric cancer patients has been improved.

Objective:To analyze the safety of paclitaxel-based, hyperthermic, intraperitoneal perfusion chemotherapy (HIPEC) after radical resection of locally advanced gastric cancer.Methods:This was a retrospective cohort study of clinicopathological data of 467 patients with locally advanced gastric adenocarcinoma who had been admitted to the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between July 2019 and April 2021. Among these patients, 151 had undergone radical resection combined with post-operative paclitaxel-based HIPEC (surgery+HIPEC group) and 316 radical resection alone (surgery group). The adverse perioperative events in study patients were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) published by the U.S. Department of Health and Human Services. Subgroup analysis was performed on patients in the surgery+HIPEC group according to the number of times HIPEC was administered and the incidence of adverse events was compared between subgroups using the χ 2 test. Independent risk factors for paclitaxel-based HIPEC-associated adverse events were identified by applying a logistic model. Results:In the surgery+HIPEC group, there were 113 (74.8%) male and 38 (25.2%) female patients of median age 64 (55, 68) years, 18 (11.9%), 79 (52.3%), and 54 (35.8%) of whom had undergone one, two, and three paclitaxel-based HIPEC treatments, respectively, after surgery. The median maximum tumor diameter was 5.0 (3.6, 6.5) cm. In the surgery group, there were 244 (77.2%) male and 72 (22.8%) female patients of median age 63 (54, 68) and the median maximum tumor diameter was 4.0 (3.0, 5.5) cm. In the surgery+HIPEC group, 112 patients (74.2%) had 198 Grade 2 or higher adverse perioperative events, postoperative hypoalbuminemia being the commonest (85 cases, 56.3%), followed by postoperative anemia (50 cases, 33.1%). Compared with the surgery group, the incidences of postoperative hypoalbuminemia (56.3% [85/151] vs. 37.7% [119/316], χ 2=14.420, P<0.001), anemia (33.1% [50/151] vs. 22.5% [71/316], χ 2=6.030, P=0.014), abdominal pain [7.3% [11/151] vs. 1.6% [5/316], χ 2=10.042, P=0.002) and abdominal distension (5.3% [8/151] vs. 1.3% [4/316], χ 2=5.123, P=0.024) were all significantly higher in the surgery+HIPEC group. Analysis of the three HIPEC subgroups revealed significant differences in the incidences of postoperative hypoalbuminemia (13/18 vs. 67.1% [53/79] vs. 35.2% [19/54], χ 2=12.955, P<0.001) and pulmonary infection (6/18 vs. 6.3% [5/79] vs. 1.9% [1/54], χ 2=13.232, P<0.001) between them. Univariate analysis identified body mass index, Borrmann's type and number of HIPEC treatments as associated with perioperative adverse events in the surgery+HIPEC group ( P<0.05). However, according to multifactorial logistic analysis, the above factors were not independent risk factors for perioperative adverse events in the surgery+HIPEC group ( P>0.05). Conclusions:Paclitaxel-based HIPEC after radical resection significantly increases the risk of postoperative hypoalbuminemia, anemia, abdominal pain, and abdominal distension in patients who have undergone excision of locally advanced gastric cancer. However, increasing the frequency of HIPEC treatments did not significantly increase the risk of paclitaxel-based HIPEC-related adverse events. Moreover, univariate and multivariate analysis did not identify any independent risk factors for paclitaxel HIPEC-related adverse events.

Colorectal cancer （CRC） is a common malignant tumor of the digestive tract with high morbidity and mortality. Although existing treatments can prolong the survival of patients， problems such as low quality of life， obvious side effects， and unsatisfactory clinical efficacy still exist， which cannot fully satisfy the overall needs of patients. For this reason， it is crucial to explore the mechanism underlying the development of CRC and to identify new treatment strategies. In recent years， with the deepening of research， ferroptosis has been gradually proven to effectively inhibit the proliferation and metastasis of CRC cells， overcome tumor drug resistance， enhance anti-tumor efficacy， and prevent tumor progression and recurrence. Therefore， regulating ferroptosis is expected to become a new strategy for the treatment of CRC. Traditional Chinese medicine （TCM） has been widely used in CRC treatment due to its advantages of multiple components， multiple targets， low drug resistance， and few side effects， and has gradually become a current research hotspot. Extensive studies have shown that TCM active ingredients and compound formulae can regulate ferroptosis-related pathways， such as iron metabolism， lipid metabolism， the cystine/glutamate antiporter system X_c^- （System X_c^-）/glutathione （GSH）/glutathione peroxidase 4 （GPX4）， ferroptosis suppressor protein 1 （FSP1）/coenzyme Q₁₀ （CoQ₁₀）/nicotinamide adenine dinucleotide phosphate ［NAD（P）H］， tumor protein 53 （p53）， nuclear factor erythroid-2-related factor 2 （Nrf2）， and non-coding RNA pathways to inhibit the growth and proliferation of CRC， thereby exerting anti-tumor effects. This review systematically summarized the mechanisms of ferroptosis related to CRC， therapeutic targets and prognosis-related markers associated with ferroptosis in CRC， and research progress on TCM targeting and regulating ferroptosis for CRC intervention， aiming to provide new perspectives and a theoretical basis for the prevention and treatment of CRC with TCM.