Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer.

KRASG12C inhibitors (adagrasib and sotorasib) have shown clinical promise in targeting KRASG12C-mutated lung cancers; however, most patients eventually develop resistance. In lung patients with adenocarcinoma with KRASG12C and STK11/LKB1 co-mutations, we find an enrichment of the squamous cell carcinoma gene signature in pre-treatment biopsies correlates with a poor response to adagrasib. Studies of Lkb1-deficient KRASG12C and KrasG12D lung cancer mouse models and organoids treated with KRAS inhibitors reveal tumors invoke a lineage plasticity program, adeno-to-squamous transition (AST), that enables resistance to KRAS inhibition. Transcriptomic and epigenomic analyses reveal ΔNp63 drives AST and modulates response to KRAS inhibition. We identify an intermediate high-plastic cell state marked by expression of an AST plasticity signature and Krt6a. Notably, expression of the AST plasticity signature and KRT6A at baseline correlates with poor adagrasib responses. These data indicate the role of AST in KRAS inhibitor resistance and provide predictive biomarkers for KRAS-targeted therapies in lung cancer.

Proteomic mapping and optogenetic manipulation of membrane contact sites.

Membrane contact sites (MCSs) mediate crucial physiological processes in eukaryotic cells, including ion signaling, lipid metabolism, and autophagy. Dysregulation of MCSs is closely related to various diseases, such as type 2 diabetes mellitus (T2DM), neurodegenerative diseases, and cancers. Visualization, proteomic mapping and manipulation of MCSs may help the dissection of the physiology and pathology MCSs. Recent technical advances have enabled better understanding of the dynamics and functions of MCSs. Here we present a summary of currently known functions of MCSs, with a focus on optical approaches to visualize and manipulate MCSs, as well as proteomic mapping within MCSs.

Gold nanoparticles with helical surface structure transformed from chiral molecules for SERS-active substrates preparation.

Surface-enhanced Raman scattering (SERS) technique has enlarged the application of Raman spectroscopy, and the most crucial problem is the exploration of SERS-active materials. In the paper, a SERS substrate made of helical gold nanoparticles by the directed synthesis of L-glutathione (L-GSH) was proposed. Because of the large surface specific area and the uneven conduction electrons distribution for sharp tips resulted from the complex concave surface and the symmetry breaking structure, The nanostructure has shown an impressive average enhancement factor (EF) of 2.95 × 105 under off-resonant condition. This phenomenon was explained by the experimental results and finite difference time domain (FDTD) method. Finally, the SERS substrates were used to detect thiram on pear with a limit of detection (LOD) of 0.62 mg/kg and R2 of 0.9772. The proposed SERS substrates suggest the potential application of chiral molecules such as amino acids, peptides et al. in the SERS-active materials fabrication.

First-Principles Study of Electronic Properties of Substitutionally Doped Monolayer SnP3.

SnP3 has a great prospect in electronic and thermoelectric device applications due to its moderate band gap, high carrier mobility, absorption coefficients, and dynamical and chemical stability. Doping in two-dimensional semiconductors is likely to display various anomalous behaviors when compared to doping in bulk semiconductors due to the significant electron confinement effect. By introducing foreign atoms from group III to VI, we can successfully modify the electronic properties of two-dimensional SnP3. The interaction mechanism between the dopants and atoms nearby is also different from the type of doped atom. Both Sn7BP24 and Sn7NP24 systems are indirect bandgap semiconductors, while the Sn7AlP24, Sn7GaP24, Sn7PP24, and Sn7AsP24 systems are metallic due to the contribution of doped atoms intersecting the Fermi level. For all substitutionally doped 2D SnP3 systems considered here, all metallic systems are nonmagnetic states. In addition, monolayer Sn7XP24 and Sn8P23Y may have long-range and local magnetic moments, respectively, because of the degree of hybridization between the dopant and its adjacent atoms. The results complement theoretical knowledge and reveal prospective applications of SnP3-based electrical nanodevices for the future.

Optical Sensors and Actuators for Probing Proximity-Dependent Biotinylation in Living Cells.

Proximity-dependent biotinylation techniques have been gaining wide applications in the systematic analysis of protein-protein interactions (PPIs) on a proteome-wide scale in living cells. The engineered biotin ligase TurboID is among the most widely adopted given its enhanced biotinylation efficiency, but it faces the background biotinylation complication that might confound proteomic data interpretation. To address this issue, we report herein a set of split TurboID variants that can be reversibly assembled by using light (designated "OptoID"), which enable optogenetic control of biotinylation based proximity labeling in living cells. OptoID could be further coupled with an engineered monomeric streptavidin that permits real-time monitoring of biotinylation with high temporal precision. These optical actuators and sensors will likely find broad applications in precise proximity proteomics and rapid detection of biotinylation in living cells.

The roles of transmembrane family proteins in the regulation of store-operated Ca2+ entry.

Store-operated Ca2+ entry (SOCE) is a major pathway for calcium signaling, which regulates almost every biological process, involving cell proliferation, differentiation, movement and death. Stromal interaction molecule (STIM) and ORAI calcium release-activated calcium modulator (ORAI) are the two major proteins involved in SOCE. With the deepening of studies, more and more proteins are found to be able to regulate SOCE, among which the transmembrane (TMEM) family proteins are worth paying more attention. In addition, the ORAI proteins belong to the TMEM family themselves. As the name suggests, TMEM family is a type of proteins that spans biological membranes including plasma membrane and membrane of organelles. TMEM proteins are in a large family with more than 300 proteins that have been already identified, while the functional knowledge about the proteins is preliminary. In this review, we mainly summarized the TMEM proteins that are involved in SOCE, to better describe a picture of the interaction between STIM and ORAI proteins during SOCE and its downstream signaling pathways, as well as to provide an idea for the study of the TMEM family proteins.

Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth.

Deregulated store-operated calcium entry (SOCE) mediated by aberrant STIM1-ORAI1 signaling is closely implicated in cancer initiation and progression. Here the authors report the identification of an alternatively spliced variant of STIM1, designated STIM1ß, that harbors an extra exon to encode 31 additional amino acids in the cytoplasmic domain. STIM1ß, highly conserved in mammals, is aberrantly upregulated in glioma tissues to perturb Ca2+ signaling. At the molecular level, the 31-residue insertion destabilizes STIM1ß by perturbing its cytosolic inhibitory domain and accelerating its activation kinetics to efficiently engage and gate ORAI calcium channels. Functionally, STIM1ß depletion affects SOCE in glioblastoma cells, suppresses tumor cell proliferation and growth both in vitro and in vivo. Collectively, their study establishes a splicing variant-specific tumor-promoting role of STIM1ß that can be potentially targeted for glioblastoma intervention.

Development of Store-Operated Calcium Entry-Targeted Compounds in Cancer.

Store-operated Ca2+ entry (SOCE) is the major pathway of Ca2+ entry in mammalian cells, and regulates a variety of cellular functions including proliferation, motility, apoptosis, and death. Accumulating evidence has indicated that augmented SOCE is related to the generation and development of cancer, including tumor formation, proliferation, angiogenesis, metastasis, and antitumor immunity. Therefore, the development of compounds targeting SOCE has been proposed as a potential and effective strategy for use in cancer therapy. In this review, we summarize the current research on SOCE inhibitors and blockers, discuss their effects and possible mechanisms of action in cancer therapy, and induce a new perspective on the treatment of cancer.

Tunable Electronic Properties of Type-II SiS2/WSe2 Hetero-Bilayers.

First-principle calculations based on the density functional theory (DFT) are implemented to study the structural and electronic properties of the SiS2/WSe2 hetero-bilayers. It is found that the AB-2 stacking model is most stable among all the six SiS2/WSe2 heterostructures considered in this work. The AB-2 stacking SiS2/WSe2 hetero-bilayer possesses a type-II band alignment with a narrow indirect band gap (0.154 eV and 0.738 eV obtained by GGA-PBE and HSE06, respectively), which can effectively separate the photogenerated electron-hole pairs and prevent the recombination of the electron-hole pairs. Our results revealed that the band gap can be tuned effectively within the range of elastic deformation (biaxial strain range from -7% to 7%) while maintaining the type-II band alignment. Furthermore, due to the effective regulation of interlayer charge transfer, the band gap along with the band offset of the SiS2/WSe2 heterostructure can also be modulated effectively by applying a vertical external electric field. Our results offer interesting alternatives for the engineering of two-dimensional material-based optoelectronic nanodevices.

PEGylated hyaluronidase/NIR induced drug controlled release system for synergetic chemo-photothermal therapy of hepatocellular carcinoma.

In recent years, cancer treatment has been facing the challenge of increasing antitumor efficiency and avoiding severe adverse effects simultaneously. In this study, we designed a controlled release drug delivery system, doxorubicin (Dox)-loaded and hyaluronic acid (HA)-modified PEGylated gold nanocages (AuNCs), which was designated as PEG-HAn-AuNCs/Dox (n represented 10n HA repeating units were modified on each AuNC). In this system, AuNCs were applied as the photothermal cores, Dox was employed as the model drug, HA was applied as the tumor-microenvironment responsive switch to achieve controlled release, and poly (ethylene glycol) (PEG) was used as the stealth polymer to prolong systemic circulation time. Firstly, we evaluated the physical and chemical properties of the PEG-HAn-AuNCs/Dox with different ratios of HA to AuNC and found that PEG-HA4-AuNCs/Dox was the optimal. Secondly, PEG-HA4-AuNCs/Dox revealed the feature of controlled release, namely, the drug release was triggered by hyaluronidase (HAase) and accelerated by the acidic pH and near-infrared (NIR) irradiation. And then PEG-HA4-AuNCs/Dox could be effectively delivered to a cultured SMMC-7721 cell line in vitro and the tumor tissues of the subcutaneous mouse models of hepatocellular carcinoma (HCC) in vivo. Finally, the results demonstrated the synergetic therapy, namely the combination of chemotherapy and photothermal therapy (PTT) (defined as chemo-photothermal therapy) mediated by PEG-HA4-AuNCs/Dox, could efficiently inhibit the tumor growth both in vitro and in vivo. Therefore, the advantages of PEG-HA4-AuNCs/Dox endowed it as a great potential candidate for HCC treatment.

Prevention of gallstones by Lidan Granule: Insight into underlying mechanisms using a guinea pig model.

The aim of the study was to examine the mechanism of action of Lidan Granule (LDG) for the prevention of gallstones using a guinea pig model. One hundred guinea pigs were divided into five groups randomly: control (standard diet and saline), model [lithogenic diet (LD) and saline], LDG-H (LD and 2 g/kg of LDG), LDG-L (LD and 1 g/kg of LDG), and ursodeoxycholic acid (UDCA) (LD and UDCA) as the positive control. At 6 weeks, the rate of gallstone formation and weight of the adrenal gland were recorded and serum levels of inflammatory cytokines were measured. Levels of corticotrophin-releasing hormone (CRH) in the hypothalamus, adrenocorticotropic hormone (ACTH) in the hypophysis, and serum cortisol were determined. Bile components were tested with colorimetry. At 6 weeks, the rate of gallstone formation was significantly decreased in the LDG-H (14.29%) and LDG-L (21.43%) groups compared to the model group (81.25%; P<0.01). LDG treatment decreased the serum levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α (P<0.01). LDG decreased bile cholesterol and increased bile acid and phospholipid levels in the bile (P<0.01). LDG treatment recovered the function of the hypothalamic-pituitary-adrenal (HPA) axis by increasing the expression of CRH (P<0.01) and ACTH (P<0.05). LDG made the bile less lithogenic, improved the function of the HPA axis, and regulated the expression of inflammatory cytokines for the prevention of cholelithiasis.

[Randomized controlled clinical trials of individualized treatment of cerebral palsy children by warm-reinforcing needling combined with Bobath rehabilitation training].

OBJECTIVE: To observe the effect of warm-reinforcing needling combined with modern rehabilitation training on motor function of cerebral palsy (CP) children. METHODS: Sixty cases of CP children were randomly divided into acupuncture combined with rehabilitation (Acu + Rehab, n = 30) group and Rehab (n = 30) group. Patients of the Acu + Rehab group were treated by warm-reinforcing needling stimulation of Jiaji (EX-B 2), Jianyu (LI 15), Quchi (LI 11), Hegu (LI 4), Zusanli (ST 36), Yinlingquan (GB 34), Sanyinjiao (SP 6), Juegu (GB 39), Yanglingquan (GB 34), etc., combined with Bobath rehabilitation therapy, and those of the Rehab group treated by Bobath rehabilitation (stimulating key control points in the body, triggering reflexes that provide head and body control). The treatment was conducted every day,with three months being a therapeutic course,two courses in all. The Peabody Developmental Motor Scales 2 (PDMS-2) was used to evaluate the CP children's motor function [1) gross motor: posture (straightness ratio), locomotion and object manipulation; 2) fine motor: grasping and visual-Motor integration]. RESULTS: After the treatment, of the 30 and 30 cases in the Acu+ Rehab and Rehab groups, 1 (3.33%) and 0 (0%) were cured, 20 (66.67%) and 18 (60.00%) experienced marked improvement, 9 (30.00%) and 12 (40.00%) were invalid, with the effective rates being 70.00% and 60.00% respectively. The therapeutic effect of the Acu + Rehab group was markedly superior to that of the Rehab group (P < 0.05). After 6 months ' treatment, the scores of posture, locomotor, object manipulation and grasping, and visual-movement integration were significantly increased in comparison with pre-treatment in the same one group (P < 0.05), and the effects of the Acu + Rehab group were obviously superior to those of Rehab group in increasing the scores of posture, locomotor, object manipulation and grasping after 6 months' treatment (P < 0.05). CONCLUSION: Warm-reinforcing needling combined with Bobath rehabilitation has a better therapeutic effect in improving gross motor and fine motor functions of CP children.

[Effects of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke: a randomized and controlled study].

OBJECTIVE: To verify the improvement function of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke. METHODS: Eighty cases were randomly divided into a warming-reinforcing acupuncture combined with rehabilitation training group (group A) and a rehabilitation training group (group B), 40 cases in each group. Both groups were treated with internal routine treatment. The Motor Relearning Program rehabilitation was used in group B, while warming-reinforcing acupuncture combined with Motor Relearning Program rehabilitation were used in group A. Jianyu (LI 15), Quchi (LI 11), Hegu (LI 4), Yanglingquan (GB 34), Yinlingquan (SP 9), Zusanli (ST 36), Sanyinjiao (SP 6) were selected, and warming-reinforcing method was used in these points, they were treated for 3 weeks. The neurological functional deficits scores of hemiparalysis patients, Fugl-Meyer Score, Motor Function Assessment Score (MAS), Barthel Index and Mini-mental State Examination (MMSE) were used to evaluate the condition of hemiparalysis patients before and after treatment. RESULTS: The effective rate of group A (87.5%, 35/40) superior to that of group B (67.5%, 27/40) (P < 0.05). The neurological functional deficit scores, Fugl-Meyer score, MAS and Barthel Index of both groups were improved after treatment (P < 0.01, P < 0.05), and the improved degree of group A was better than that of group B (P < 0.01, P < 0.05). CONCLUSION: There is obvious improvement function of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke, and the function is better than that of simple rehabilitation training.

[Effect of heat-reinforcing needling combined with rehabilitation training on the motor function of ischemic stroke patients].

OBJECTIVE: To observe the therapeutic effect of heat-reinforcing needling combined with modem rehabilitation training on the motor function of ischemic stroke patients. METHODS: Fifty case of ischemic stroke patients were randomly divided into rehabilitation (Rehab, n=40) and acupuncture (Acup) + Rehab (n=40) groups. Heat-reinforcing needling was applied to Jianyu (LI 15), Quchi (LI 11), Hegu (LI 14), Zusanli (ST 36), Yanglingquan (GB 34), Yinlingquan (SP 9) and Sanyinjiao (SP 6), once daily for 3 weeks. Rehabilitation training including healthy limb and joint movement was conducted, once daily for 3 weeks. The patient's neurological impairment degree and the motor function (Fugl-Meyer index) were evaluated before and after the treatment. RESULTS: After the treatment, of the each 40 cases in Rehab and Acup + Rehab groups, 10 (25.0%) and 17 (42.5%) experienced marked improvement in their symptoms, 17 (42.5%) and 18 (45.0%) had improvement, 13 (32.5%) and 5 (12.5%) failed, with the effective rates being 67.5% and 87.5% respectively. The therapeutic effect of Acup + Rehab group was markedly superior to that of Rehab group (P<0.05). Comparison between two groups showed no significant differences in the scores of clinical neurological impairment degree and the scores of Fugl-Meyer index before the treatment (P>0.05). After the treatment, the scores of neurological impairment degree of two groups both decreased significantly (P<0.05), and the scores of the Fugl-Meyer index of the upper and lower limbs increased significantly in two groups (P<0.05). The score of neurological impairment degree of Acup + Rehab group was significantly lower than that of Rehab group (P<0.05), while the scores of the Fugl-Meyer index of two limbs of Acup + Rehab group were obviously higher than those of Rehab group (P<0.01). CONCLUSION: The therapy of heat-reinforcing needling combined with rehabilitation training is significantly superior to that of simple rehabilitation training in improving neurological impairment and motor function of ischemic stroke patients.

[Clinical study of the treatment of infant cerebral palsy with warm-reinforcing needling combined with rehabilitation training].

OBJECTIVE: To observe the therapeutic effect of warm-reinforcing needling combined with modern rehabilitation training for infant cerebral palsy (CP). METHODS: Forty cases of cerebral palsy children were randomly divided into rehabilitation (Rehab, n=19) and acupuncture (Acup) + Rehab (n=21) groups. Body acupoints used were Baihui (GV 20), Zusanli (ST 36), Quchi (LI 11), Huantiao (GB 30), Yinlingquan (GB 34), Sanyinjiao (SP 6), etc., and scalp-acupoints Zhisanzhen (the cross-point between the anterior hairline and the median line of the head, 3 cun bilateral to the crossing point), Naosanzhen [Nao-hu (GV 17), 1.5 cun bilateral to GV17], Balance Zone, Motor Zone, etc. . The treatment was conducted once every other day, with 3 months being a therapeutic course, 2 courses altogether. Rehabilitation training included physical training (PT), occupational therapy (OT) training, and speech training (ST), 5 times a week, with 3 months being a therapeutic course, 2 courses altogether. Gross motor function measure (GMFM) and comprehensive function (CF, including cognition, speech, motor, self-care and social-adaptable abilities) were evaluated. RESULTS: After the treatment, of the 19 and 21 cases in Rehab and Acup+ Rehab groups, 12 (63.16%) and 18 (85.71%) experienced marked improvement, 7 (36.84%) and 3 (14.29%) failed, with the effective rates being 63.16% and 85.71% respectively. The therapeutic effect of Acup+ Rehab group was markedly superior to that of Rehab group (P < 0.05). Self-comparison of two groups showed that the scores of CF and GMFM increased significantly in comparison with pre-treatment (P < 0.01), and the scores of F and GMFM of Acup + Rehab group were obviously higher than those of Rehab group (P < 0.01). CONCLUSION: Rehabilitation training combined with acupuncture can apparently improve CP children's motor and comprehensive functions, and the therapeutic effect of AcupWarm-reinf Rehab is evidently superior to that of simple rehabilitation training therapy.

[Experimental study on the prevention and treatment effects of warm-reinforcing needling for hyperlipoidemia in the rabbit].

OBJECTIVE: To investigate the effect of warm-reinforcing needling (WRN) on serum lipid metabolism in hyperlipoidemia (HL) rabbits. METHODS: A total of 32 rabbits were randomly and evenly divided into control group, WRN group, model group and uniform reinforcing-reducing needling (URRN) group. HL model was established by feeding the rabbits with hypercholesterol and high-fat forage continuously for 7 weeks. For rabbits of WRN and URRN groups, "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Xuehai" (SP 10) were punctured and stimulated manually with WRN and URRN techniques respectively, once daily, continuously for 7 weeks. At the end of experiments, blood samples were collected from the heart, and centrifuged for detecting serum total cholesterol (TC) triglyceride (TG) and high density lipoprotein (HDL) with enzyme method, and platelet aggregation rate (PAR) with an intelligent blood agglutometer. Low density lipoprotein (LDL) = TC- (HDL + TG/2.2). RESULTS: Compared with normal control group, serum TC, TG and LDL contents in model group, WRN and URRN groups increased significantly (P < 0.01), and HDL content of model group decreased considerably (P < 0.01); while in comparison with model group, serum TC, LDL and TG contents of WRN and URRN groups decreased considerably (P < 0.01), and serum HDL levels of WRN and URRN groups increased significantly (P < 0.01). Serum TC content of WRN group was markedly lower than that of URRN group (P < 0.05), and HDL of WRN group was remarkably higher than that of URRN group (P < 0.01). In comparison with normal control group, 1 min, 5 min and maximum PARs in model, WRN and URRN groups increased significantly (P < 0.01), while in comparison with model group, 1 min, 5 min and maximum PARs of WRN and URRN groups decreased considerably (P < 0.01). In addition, 1 min and maximum PARs in WRN group were markedly lower than those in URRN group (P < 0.05). Light microscopic observation showed that the apoptotic foam cells in the lipid plaque of aorta wall in model group appeared and were obviously more than those of WRN and URRN groups. CONCLUSION: Acupuncture can effectively lower serum TC, LDL and TG levels, raise serum HDL content, and suppress platelet aggregation, and the therapeutic effect of WRN is significantly superior to that of URRN, which may contribute to the action of acupuncture in regulating blood lipid and inhibiting the formation of atheromatous plaque.

[Protective and therapeutic effects of Shugan Lifei Recipe on rats with asthma under stress and the mechanisms].

OBJECTIVE: To explore the influence of psychological factor on asthma, the protective and therapeutic effects of Shugan Lifei Recipe on rats with asthma under stress and the mechanisms. METHODS: Allergy and stress-induced asthma models were established in rats by giving ovalbumin and restraining stress. Radioimmunoassay, enzyme linked immunosorbent assay, in situ hybridization and immunohistochemical method were used to detect plasma corticosterone, IL-4, IFN-gamma, expression of glucocorticoid receptor (GR) mRNA in hippocampus and adrenocorticotropic hormone corticoliberin (CRH) positive neuron in hypothalamus. Optical and electron microscopes were used to observe the morphological changes of pulmonary hilar and hippocampal tissues. RESULTS: Shugan Lifei Recipe (SGLFR) could reduce plasma corticosterone, decrease CRH positive neurons in paraventricular nucleus of hypothalamus, up-regulate the expression of GR mRNA in hippocampus and reduce the injury of hippocampal neuron. SGLFR had certain inhibitive effect on hyperfunction of hypothalamo-pituitary-adrenal cortex (HPA) axis in rats with asthma under stress and could also relieve the pathological changes of the pulmonary hilar tissue. The level of plasma IFN-gamma was increased while the level of plasma IL-4 was decreased in SGLFR-treated group. CONCLUSION: The mechanism of SGLFR in treating the rats with asthma under stress is probably to regulate the hyperfunction of HPA axis and the disorder of immuo-system.

[Experimental study of apoptosis and proliferation of gastric mucosal cells in chronic atrophic gastritis].

OBJECTIVE: To study the relationship between long-term high-salt hot diet and chronic atrophic gastritis (CAG). The expression of apoptosis cells, proliferation cells, bcl-2 and Fas proteins were detected in the gastric mucosa of CAG rates induced by high-salt hot water. METHODS: TUNEL technique and immunohistochemical method were used in the experiment. Flow cytometry method was used to detect the DNA content of apoptosis cells. RESULTS: (1) The detection of apoptosis with TUNEL showed that the apoptosis cells in CAG rates induced by high-salt hot water were high. These cells could be seen in all layers of gastric mucosa, apoptosis index of model rates was higher than that of normal rates (P < 0.05). (2) The result of detecting apoptosis gene and proliferating cell nuclear antigen (PCNA) by immunohistochemical method showed that the expression of bcl-2, Fas and PCNA in the CAG rates induced by high-salt hot water was much higher than that of normal gastric mucosa (P < 0.05). The expression rates of bcl-2, Fas proteins were higher with time going on. After being given high-salt hot water intragastrically for 4, 8, 12 weeks, the bcl-2 protein expression rates were 12.5%, 16.7%, 76.5%, the Fas protein expression rates were 18.7%, 22.2% and 64.7%. (3) Flow cytometry technique showed that there was a second G(0)/G(1) peek, which was apoptosis cells peak, but was not seen in the normal gastric mucosa. CONCLUSIONS: Abnormality of proliferation and apoptosis in gastric mucosa could be induced by high-salt hot water. bcl-2, Fas gene played an important role in this course.