OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia （FD） in rats. METHODS In safety test， 40 rats were divided into blank control group， Shuangshu decoction low-dose， medium- dose and high-dose groups [108， 216， 324 g/（kg·d）， calculated by raw medicine， the same applies below]； they were given relevant medicine intragastrically， for continuous 14 days. The mortality and toxic reactions of rats were recorded， and the organ indexes of the liver， kidney， spleen， lung and heart of rats were calculated； the pathological morphological changes in the liver， kidney， spleen， lung， heart， stomach， duodenum， and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded， and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed， and blood routine and serum biochemical indicators were measured， in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group， model group， and Shuangshu decoction low-， medium-， and high-dose groups （9.45， 18.9， 37.8 g/kg）， with 10 rats in each group. Except for blank control group， rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide （3.5 mg/kg）. Rats in each group were administered the corresponding drug solution/normal saline intragastrically， once a day， for 14 consecutive days. After the last medication， fecal moisture content， intestinal propulsion rate， gastric emptying rate and serum level of motilin were all detected， and interstitial cell of Cajal （ICC） ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group， and no significant difference was found in organ coefficient， routine blood and serum biological index， compared to blank control group （P＞0.05）； no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that， compared with the blank control group， the fecal moisture content， gastric emptying rate， intestinal propulsion rate， and serum motilin levels in the model group were significantly decreased （P＜0.05）； in the colonic tissue， the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae， and the endoplasmic reticulum was dilated. Compared with model group， the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators （P＜ 0.05）； additionally， there was a large number of mitochondria in the ICC of the colonic tissue， with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats； its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion， as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.

OBJECTIVE To investigate the inhibitory effect and mechanism of Modified qifang weitong granules on gastric cancer based on in vitro and in vivo experiments. METHODS Human gastric cancer HGC-27 cells were divided into the following groups: control group （treated with fetal bovine serum）， 10% drug-containing serum group， 15% drug-containing serum group， 20% drug-containing serum group， and 5-fluorouracil （5-Fu） group （positive control， 3.90 μg/mL）. After culturing the cells in each group with the corresponding serum/drug solution， their proliferation， migratory and invasive abilities， as well as the cell cycle， were assessed. Additionally， the expression levels of epithelial-mesenchymal transition （EMT）-related proteins [E-cadherin， N-cadherin， and vimentin] in the cells were measured. Logarithmic-phase HGC-27 cells were harvested and subcutaneously injected into the right axillary region of nude mice to establish a subcutaneous xenograft tumor model in nude mice. The successfully modeled tumor-bearing nude mice were randomly divided into model group， low-， medium- and high-dose groups of Modified qifang weitong granules （17.65， 35.29 and 70.58 g/kg， respectively）， and 5-Fu group （25 mg/kg）， with 5 mice in each group. After 14 days of treatment with the corresponding drugs in each group， the histopathological morphology of the tumor tissues in the nude mice was observed. Immunohistochemistry and Western blot assay were employed to detect the expression levels of EMT- related proteins in the tumor tissues of the nude mice. RESULTS In the cell experiment， compared with the control group， the cell proliferation rate， migration rate， number of invasive cells， as well as the expression levels of N-cadherin and vimentin proteins， and the percentage of cells in the G2/M phase were all significantly decreased/reduced in the 15% drug-containing serum group， 20% drug-containing serum group （P＜0.05）. Conversely， the percentage of cells in the G0/G1 phase and the expression level of E- cadherin protein were significantly increased （P＜0.05）. In animal experiment， compared with the model group， the high-dose group of Modified qifang weitong granules exhibited significantly reduced tumor mass and expression levels of N-cadherin and vimentin proteins in the tumor tissues of nude mice （P＜0.05）， while the expression level of E-cadherinprotein in the tumor tissues was significantly increased （P＜0.05）. Additionally， the tumor cells varied in size and showed extensive necrosis. CONCLUSIONS Modified qifang weitong granules effectively inhibit gastric cancer in both in vitro and in vivo models， and the mechanism of action is related to the suppression of EMT.

OBJECTIVES: To explore the mechanism of Shuangshu Decoction (SSD) for inhibiting growth of gastric cancer xenografts in nude mice. METHODS: Network pharmacology analysis was conducted to identify the common targets of SSD and gastric cancer cell ferroptosis, and bioinformatics analysis and molecular docking were used to validate the core targets. In the cell experiment, AGS cells were treated with SSD-medicated serum, Fer-1 (a ferroptosis inhibitor), or both, and the changes in cell viability, ferroptosis markers (ROS, Fe²⁺ and GSH), expressions of P53, SLC7A11 and GPX4, and mitochondrial morphology were examined. In a nude mouse model bearing gastric cancer xenografts, the effects of gavage with SSD, intraperitoneal injection of Fer-1, or their combination on tumor volume/weight, histopathology, and expressions of P53, SLC7A11 and GPX4 levels were evaluated. RESULTS: The active components in SSD (quercetin and wogonin) showed strong binding affinities to P53. In AGS cells, SSD treatment dose-dependently inhibited cell proliferation, increased ROS and Fe²⁺ levels, upregulated P53 expression, and downregulated the expressions of SLC7A11 and GPX4, but these effects were effectively attenuated by Fer-1 treatment. SSD also induced mitochondrial shrinkage and increased the membrane density, which were alleviated by Fer-1. In the tumor-bearing mouse models, gavage with SSD significantly reduced tumor size and weight, caused tumor cell necrosis, upregulated P53 and downregulated SLC7A11 and GPX4 expression in the tumor tissue, and these effects were obviously mitigated by Fer-1 treatment. CONCLUSIONS SSD inhibits gastric cancer growth in nude mice by inducing cell ferroptosis via the P53/SLC7A11/GPX4 axis.
Ferroptosis/drug effects* ; Animals ; Stomach Neoplasms/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Mice, Nude ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Amino Acid Transport System y+/metabolism* ; Mice ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Xenograft Model Antitumor Assays

Objective To explore the mechanism of Shuangshu Decoction(SSD)for inhibiting growth of gastric cancer xenografts in nude mice.Methods Network pharmacology analysis was conducted to identify the common targets of SSD and gastric cancer cell ferroptosis,and bioinformatics analysis and molecular docking were used to validate the core targets.In the cell experiment,AGS cells were treated with SSD-medicated serum,Fer-1(a ferroptosis inhibitor),or both,and the changes in cell viability,ferroptosis markers(ROS,Fe2+and GSH),expressions of P53,SLC7A11 and GPX4,and mitochondrial morphology were examined.In a nude mouse model bearing gastric cancer xenografts,the effects of gavage with SSD,intraperitoneal injection of Fer-1,or their combination on tumor volume/weight,histopathology,and expressions of P53,SLC7A11 and GPX4 levels were evaluated.Results The active components in SSD(quercetin and wogonin)showed strong binding affinities to P53.In AGS cells,SSD treatment dose-dependently inhibited cell proliferation,increased ROS and Fe2+levels,upregulated P53 expression,and downregulated the expressions of SLC7A11 and GPX4,but these effects were effectively attenuated by Fer-1 treatment.SSD also induced mitochondrial shrinkage and increased the membrane density,which were alleviated by Fer-1.In the tumor-bearing mouse models,gavage with SSD significantly reduced tumor size and weight,caused tumor cell necrosis,upregulated P53 and downregulated SLC7A11 and GPX4 expression in the tumor tissue,and these effects were obviously mitigated by Fer-1 treatment.Conclusion SSD inhibits gastric cancer growth in nude mice by inducing cell ferroptosis via the P53/SLC7A11/GPX4 axis.

To study the correlation between the level of Bordetella pertussis nucleic acid and clinical features of the disease in infants and young children and to investigate the risk factors for the development of severe pertussis. Using retrospective research methods, children aged 1 month-3 years who came to Hunan Children′s Hospital from August 2023 to February 2024 and were diagnosed with pertussis for analysis. According to the logarithmic value of BP-DNA (log 10 copies/ml), 35 cases were divided into the low load group, 78 cases were divided into the medium load group and 94 cases were divided into the high load group; 54 cases were divided into the severe whooping cough group and 153 cases were divided into the general group according to the severity of the disease; the clinical characteristics and laboratory data of the groups were compared, and the risk factors for the occurrence of severe whooping cough were analyzed at the same time. The ROC was used to evaluate the predictive efficacy of BP-DNA and WBC count for the development of severe pertussis. The results showed that in the high-dose group, the WBC count(22.59×10 9/L), L/N ratio(3.31), and hospitalization days(9.0 d) were significantly higher than those in the medium-dose group and low-dose group ( F=6.309, 2.825, 15.149, all P<0.05). The hospitalization rate (100%), combined infection rate (64.96%), incidence of severe whooping cough (31.9%), pyrexia rate (29.8%), and corticosteroid use rate (57.4%) were also significantly higher than the other two groups ( χ2=25.977, 9.163, 9.371, 8.299, 20.332, all P<0.05), and the complete immunity rate (9.6%) was significantly lower than the other two groups ( χ2=11.632, P<0.05). Compared with the group of common whooping cough, the proportion of children under 1 year old (100%, χ2=9.581), the BP-DNA load (6.56 log 10 copies/ml, Z=4.004), the WBC count(31.34×10 9/L, t=7.513), the PCT level(0.07 ng/ml, Z=2.626), the IL-6 level (6.65 ng/ml, Z=4.336), the combined infection rate (88.9%, χ2=36.536), the incidence of wheezing or dyspnea (55.6%, χ2=42.972), the rate of no improvement of symptoms with macrolides prior to the visit (77.8%, χ2=26.266), and the incidence of fever (55.6%, χ2=42.972) were all significantly higher;the complete immunity rate was significantly lower (5.6%, χ2=9.581) in the severe whooping cough group, the differences were all statistically significant(all P<0.05).The result of logistic regression analysis showed severe elevation of BP-DNA, high leukocyte count, co-infection, wheezing or shortness of breath, pyrexia and no improvement of symptoms with macrolides before the treatment were the risk factors for the development of severe pertussis and the logistic regressive model predicts a sensitivity and specificity of 0.83 and 0.90 for severe whooping cough, respectively. The sensitivity of BP-DNA>1.91×10 6 copies/ml, WBC count >19.97×10 9/L and the binominal combined test to predict the occurrence of severe pertussis were 0.87, 0.61 and 0.80, and the specificity were 0.43, 0.86 and 0.73, respectively. In conclusion, nucleic acid load in infants with pertussis correlated with clinical characteristics such as the active immunity status, fever, co-infections and hospitalisation and days in hospital. Children with high nucleic acid load, high white blood cell counts, co-infections, fever and no improvement of symptoms with macrolides prior to seeing a doctor were more likely to develop the severe pertussis. When BP-DNA >1.91×10 6 copies/ml or WBC counts>19.97×10 9/L, they have the highest predictive efficacy for severe pertussis respectively, and combined detection is better.

To study the correlation between the level of Bordetella pertussis nucleic acid and clinical features of the disease in infants and young children and to investigate the risk factors for the development of severe pertussis. Using retrospective research methods, children aged 1 month-3 years who came to Hunan Children′s Hospital from August 2023 to February 2024 and were diagnosed with pertussis for analysis. According to the logarithmic value of BP-DNA (log 10 copies/ml), 35 cases were divided into the low load group, 78 cases were divided into the medium load group and 94 cases were divided into the high load group; 54 cases were divided into the severe whooping cough group and 153 cases were divided into the general group according to the severity of the disease; the clinical characteristics and laboratory data of the groups were compared, and the risk factors for the occurrence of severe whooping cough were analyzed at the same time. The ROC was used to evaluate the predictive efficacy of BP-DNA and WBC count for the development of severe pertussis. The results showed that in the high-dose group, the WBC count(22.59×10 9/L), L/N ratio(3.31), and hospitalization days(9.0 d) were significantly higher than those in the medium-dose group and low-dose group ( F=6.309, 2.825, 15.149, all P<0.05). The hospitalization rate (100%), combined infection rate (64.96%), incidence of severe whooping cough (31.9%), pyrexia rate (29.8%), and corticosteroid use rate (57.4%) were also significantly higher than the other two groups ( χ2=25.977, 9.163, 9.371, 8.299, 20.332, all P<0.05), and the complete immunity rate (9.6%) was significantly lower than the other two groups ( χ2=11.632, P<0.05). Compared with the group of common whooping cough, the proportion of children under 1 year old (100%, χ2=9.581), the BP-DNA load (6.56 log 10 copies/ml, Z=4.004), the WBC count(31.34×10 9/L, t=7.513), the PCT level(0.07 ng/ml, Z=2.626), the IL-6 level (6.65 ng/ml, Z=4.336), the combined infection rate (88.9%, χ2=36.536), the incidence of wheezing or dyspnea (55.6%, χ2=42.972), the rate of no improvement of symptoms with macrolides prior to the visit (77.8%, χ2=26.266), and the incidence of fever (55.6%, χ2=42.972) were all significantly higher;the complete immunity rate was significantly lower (5.6%, χ2=9.581) in the severe whooping cough group, the differences were all statistically significant(all P<0.05).The result of logistic regression analysis showed severe elevation of BP-DNA, high leukocyte count, co-infection, wheezing or shortness of breath, pyrexia and no improvement of symptoms with macrolides before the treatment were the risk factors for the development of severe pertussis and the logistic regressive model predicts a sensitivity and specificity of 0.83 and 0.90 for severe whooping cough, respectively. The sensitivity of BP-DNA>1.91×10 6 copies/ml, WBC count >19.97×10 9/L and the binominal combined test to predict the occurrence of severe pertussis were 0.87, 0.61 and 0.80, and the specificity were 0.43, 0.86 and 0.73, respectively. In conclusion, nucleic acid load in infants with pertussis correlated with clinical characteristics such as the active immunity status, fever, co-infections and hospitalisation and days in hospital. Children with high nucleic acid load, high white blood cell counts, co-infections, fever and no improvement of symptoms with macrolides prior to seeing a doctor were more likely to develop the severe pertussis. When BP-DNA >1.91×10 6 copies/ml or WBC counts>19.97×10 9/L, they have the highest predictive efficacy for severe pertussis respectively, and combined detection is better.

Originating from Treatise on Cold Damage （ZHANG Zhongjing）， Wumeiwan is a representative prescription for pungent dispersing and bitter descending， upper clearing and warm purging， and combining cold and warm， which can be used to treat abdominal pain， enduring diarrhea， and syncope caused by cold and heat in complexity and asthenia in origin and sthenia in superficiality. Owing to the remarkable clinical efficacy， it is widely applied to the treatment of various internal injuries and external-contraction diseases. In recent years， the incidence of diseases of large intestine such as ulcerative colitis， Crohn's disease， and colorectal cancer has been on the rise， threatening the quality of life and health of patients. Major headway has been made in the clinical research on the treatment of the above diseases with Wumeiwan and on the mechanisms. However， no relevant summary is available， leading to the failure of further excavation and utilization of the value of this prescription in the treatment of the above diseases in time. Therefore， this paper reviews the theoretical basis， clinical research， and mechanism research of Wumeiwan and its modified formulas in the treatment of diseases of large intestine in recent years. The literature research suggests that Wumeiwan can effectively relieve clinical symptoms and reduce recurrence rate of large intestine diseases （including ulcerative colitis， Crohn's disease， diarrhea-predominant irritable bowel syndrome， colorectal cancer， chemotherapy-induced intestinal mucositis， and postoperative colorectal adenoma） with little adverse reactions. At the moment， the mechanisms of Wumeiwan against the above diseases are anti-inflammatory response， regulating immune function， repairing intestinal mucosal barrier， anti-tumor， regulating intestinal flora， anti-oxidative damage， analgesia， and inhibiting colonic epithelial cell apoptosis， but the specific molecular mechanism should be further explored. Through literature research， this paper comprehensively analyzes the theoretical basis， clinical research， and mechanisms of Wumeiwan in the treatment of diseases of large intestine， which is expected to serve as a reference for the further research on Wumeiwan in the prevention and treatment of diseases of large intestine and the mechanisms.

OBJECTIVES: To observe the efficacy and adverse reactions of the combination of endostar with chemotherapy in the treatment of advanced (IVb) and recurrent metastatic cervical cancer. METHODS: Forty-four patients with recurrent and metastatic cervical cancer, who were admitted to the Second Xiangya Hospital, Central South University from December 2016 to December 2018 were randomly divided into an experimental group and a control group (22 cases in each group). The control group was given gemcitabine plus cisplatin (GP) or docetaxel plus cisplatin (DP) treatment, the experimental group was treated with endostar on the basis of the control group. RESULTS: The objective response rate (ORR) was 42.9% in the experimental group and 22.7% in the control group. There was no significant difference between the 2 groups ( CONCLUSIONS Compared with chemotherapy alone, endostar combined with chemotherapy can prolong the median progression-free survival, with higher ORR and similar adverse reactions.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Cisplatin/therapeutic use* ; Endostatins ; Female ; Humans ; Lung Neoplasms/pathology* ; Neoplasm Recurrence, Local/pathology* ; Neoplasm Staging ; Recombinant Proteins ; Uterine Cervical Neoplasms

Objective:To investigate the anatomy and therapeutic effecton skin soft tissue defect at the great toe of perforator flap from distal deep branch of medial plantar artery.Methods:The arteries of one adult foot specimens were filled with red latex and vascular anatomy was performed. Branch distribution and anastomosis of medial plantar artery and dorsal foot artery were observed. The clinical data of 12 patients with skin soft tissue defect at the great toe repaired by retrograde perforator flap from distal deepbranch of medial plantar artery from September 2016 to September 2019 in Affiliated Hospital of Zunyi Medical University was selected, and the donor sites were repaired with skin grafts. The flap survival and complications were observed.Results:Anatomy result demonstrated that deep branch of the medial plantar artery was direct continuation of the medial plantar artery. It traveled along between short toe flexor muscle and abductor hallucis muscle, and gave out several perforators. The proximal perforators passed through the abductor hallucis muscle, and anastomosed with superficial branch of medial plantar artery, anterior medial malleolus artery, and medial tarsal artery. Three perforators were issued at the proximal end of the first metatarsophalangeal joint, namely articular perforator, cutaneous perforator, and communication branch. The cutaneous perforator was main blood supply source for perforator flap from distal deep branch of medial plantar artery.A total of 12 skin flaps were harvested from 12 patients, with an area from 4.5 cm×3.0 cm to 9.0 cm×6.0 cm. Postsurgery dark purple and a few blisters occurred in three flaps, and the sutures at the pedicle were immediately removed, and the flap was coated with antibiotic ointment to keep it moist, then the flap color gradually improved after postsurgery 5 days.12 skin flaps eventually survived completely. All patients were followed up by telephone for 2-12 months. The flap color, texture and appearance were excellent. The traumatic feet walked normally.Conclusions:The perforator flap from distal deep branch of medial plantar artery has reliable blood supply for retrograde repairing small and medium skin defect at the great toe of distal the first metatarsophalangeal joint, with simple operation, less trauma, and positive postoperative effect.

Objective:To investigate the anatomy and therapeutic effecton skin soft tissue defect at the great toe of perforator flap from distal deep branch of medial plantar artery.Methods:The arteries of one adult foot specimens were filled with red latex and vascular anatomy was performed. Branch distribution and anastomosis of medial plantar artery and dorsal foot artery were observed. The clinical data of 12 patients with skin soft tissue defect at the great toe repaired by retrograde perforator flap from distal deepbranch of medial plantar artery from September 2016 to September 2019 in Affiliated Hospital of Zunyi Medical University was selected, and the donor sites were repaired with skin grafts. The flap survival and complications were observed.Results:Anatomy result demonstrated that deep branch of the medial plantar artery was direct continuation of the medial plantar artery. It traveled along between short toe flexor muscle and abductor hallucis muscle, and gave out several perforators. The proximal perforators passed through the abductor hallucis muscle, and anastomosed with superficial branch of medial plantar artery, anterior medial malleolus artery, and medial tarsal artery. Three perforators were issued at the proximal end of the first metatarsophalangeal joint, namely articular perforator, cutaneous perforator, and communication branch. The cutaneous perforator was main blood supply source for perforator flap from distal deep branch of medial plantar artery.A total of 12 skin flaps were harvested from 12 patients, with an area from 4.5 cm×3.0 cm to 9.0 cm×6.0 cm. Postsurgery dark purple and a few blisters occurred in three flaps, and the sutures at the pedicle were immediately removed, and the flap was coated with antibiotic ointment to keep it moist, then the flap color gradually improved after postsurgery 5 days.12 skin flaps eventually survived completely. All patients were followed up by telephone for 2-12 months. The flap color, texture and appearance were excellent. The traumatic feet walked normally.Conclusions:The perforator flap from distal deep branch of medial plantar artery has reliable blood supply for retrograde repairing small and medium skin defect at the great toe of distal the first metatarsophalangeal joint, with simple operation, less trauma, and positive postoperative effect.