ObjectiveTo explore the mechanism of Yishen Huashi granules in alleviating renal tubular epithelial cell injury and relieving diabetic kidney disease by regulating the mitogen-activated protein kinase （MAPK） signaling pathway. MethodsThe db/db mice of 12 weeks old were randomly assigned into model ， dapagliflozin （1.6 mg·kg^-1）， and Yishen Huashi granules （4.7 g·kg^-1）， and db/m mice were used as the control group. The general conditions of mice were observed， and fasting blood glucose and 24-h urinary protein and albumin-to-creatinine ratio （ACR） were measured at weeks 0 and 12 of administration. After 12 weeks of treatment， the levels of serum creatinine （SCr）， blood urea （UREA）， triglycerides （TG）， total cholesterol （TC）， and low density lipoprotein （LDL） were measured. The pathological changes in the renal tissue were observed by hematoxylin-eosin （HE） staining， Periodic acid-Schiff （PAS） staining， Mallory staining， and transmission electron microscopy. Real-time PCR was employed to determine the mRNA levels of monocyte chemotactic protein-1 （MCP-1） and CC chemokine receptor-2 （CCR2） in the renal tissue of mice. The immunohistochemical assay was employed to examine the expression of p38， phospho-p38 （p-p38）， MCP-1， and CCR2 in the renal tissue of mice. Western blotting was employed to measure the protein levels of p-p38， p38， MCP-1， and CCR2 in the renal tissue of mice.HK-2 cells cultured in vitro were grouped as follows： negative control， high glucose（30 mmol·L^-1）， Yishen Huashi granule-containing serum， and SB203580. After 48 h of cell culture in each group， RNA were extracted and the levels of MCP-1， and CCR2 mRNA were determined by Real-time PCR，proteins were extracted and the levels of p38， p-p38， MCP-1， and CCR2 were determined by Western blot. ResultsThe in vivo experiments showed that before treatment， other groups had higher body weight， blood glucose level， 24 h urinary protein， and ACR than the control group （P<0.05，P<0.01）. After 12 weeks of treatment， compared with the model group， the Yishen Huashi granules group showed improved general conditions， a decreasing trend in body weight， lowered levels of blood glucose， 24-h urinary protein， and ACR （P<0.01）， reduced SCr and UREA （P<0.01）， and declined levels of TC， TG， and LDL （P<0.05，P<0.01）. Compared with the model group， the Yishen Huashi granules group showed alleviated damage and interstitial fibrosis in the renal tissue as well as reductions in glomerular foot process fusion and basement membrane thickening. Moreover， the Yishen Huashi granules group showed down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01）， reduced positive expression of p-p38， MCP-1， and CCR2 （P<0.01）， and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2 （P<0.05） in the renal tissue. The cell experiment showed that compared with the high glucose group， the Yishen Huashi granule-containing serum group showcased down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01） and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2（P<0.05，P<0.01）. ConclusionYishen Huashi granules can regulate glucose-lipid metabolism， reduce 24 h urinary protein and ACR， improve the renal function， alleviate the renal tubule injury caused by high glucose， and protect renal tubule epithelial cells in db/db mice by reducing MCP-1/CCR2 activation via the p38 MAPK signaling pathway.

Objective:To investigate the effect of laparoscopic splenectomy and azygoportal disconnection (LSD) on liver synthesis and development of liver cirrhosis.Methods:This is a prospective case series study.The clinical data of liver cirrhotic patients with portal hypertension who received LSD at the Department of Hepatobiliary Surgery of Northern Jiangsu People′s Hospital Affiliated to Yangzhou University from September 2014 to January 2016 were included. This study analyzed the diameter of the portal vein, the velocity of portal blood flow, the routine blood parameters, the liver function, the synthetic proteins of liver (antithrombin Ⅲ (AT-Ⅲ), protein S, protein C), and the serum content of liver fibrotic markers(collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase). Repeated measures ANOVA was used for comparison between multiple groups, and least significance difference was used for post-hoc multiple comparison.Results:A total of 106 patients were included in the study, including 70 males and 36 females, aged (51.8±9.8) years(range: 28 to 75 years).Compared with the preoperative results, the diameter of portal vein and the velocity of portal vein decreased after surgery ( F=14.03, 12.15, respectively, both P<0.01). Compared with the preoperative results, the total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score and classification were improved ( F=17.96, 56.01, 66.63, 35.83, 33.49, and 27.50, respectively, all P<0.01), and the AT-Ⅲ, protein S, protein C,collagen type Ⅳ, procollagen type Ⅲ, laminin and hyaluronidase levels were also improved ( F=47.87, 36.26, 18.02, 2.79, 14.58, 44.35, and 14.38, respectively, all P<0.01). Compared with the preoperative period, the diameter of portal vein was reduced from the first week to the 24 th month after surgery ( t=5.45 to 9.39, all P<0.01). Compared with the preoperative period, the velocity of portal vein blood from the first week after surgery to the 24 th month after surgery was decreased ( t=4.02 to 8.43, all P<0.01). Compared with the preoperative period, routine blood parameters (white blood count, hemoglobin, platelet count), liver function (total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score), liver synthetic protein (AT-Ⅲ, protein S, protein C) and liver fibrotic markers (collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase) were improved to varying degrees at the 24th month after surgery ( t=-20.46 to 11.93, all P<0.01). Conclusion:Preliminary findings show that LSD can reduce portal vein pressure, restore blood cell number, and improve liver synthesis function and the degree of liver fibrosis in patients with portal hypertension in liver cirrhosis.

Objective:To investigate the effect of laparoscopic splenectomy and azygoportal disconnection (LSD) on liver synthesis and development of liver cirrhosis.Methods:This is a prospective case series study.The clinical data of liver cirrhotic patients with portal hypertension who received LSD at the Department of Hepatobiliary Surgery of Northern Jiangsu People′s Hospital Affiliated to Yangzhou University from September 2014 to January 2016 were included. This study analyzed the diameter of the portal vein, the velocity of portal blood flow, the routine blood parameters, the liver function, the synthetic proteins of liver (antithrombin Ⅲ (AT-Ⅲ), protein S, protein C), and the serum content of liver fibrotic markers(collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase). Repeated measures ANOVA was used for comparison between multiple groups, and least significance difference was used for post-hoc multiple comparison.Results:A total of 106 patients were included in the study, including 70 males and 36 females, aged (51.8±9.8) years(range: 28 to 75 years).Compared with the preoperative results, the diameter of portal vein and the velocity of portal vein decreased after surgery ( F=14.03, 12.15, respectively, both P<0.01). Compared with the preoperative results, the total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score and classification were improved ( F=17.96, 56.01, 66.63, 35.83, 33.49, and 27.50, respectively, all P<0.01), and the AT-Ⅲ, protein S, protein C,collagen type Ⅳ, procollagen type Ⅲ, laminin and hyaluronidase levels were also improved ( F=47.87, 36.26, 18.02, 2.79, 14.58, 44.35, and 14.38, respectively, all P<0.01). Compared with the preoperative period, the diameter of portal vein was reduced from the first week to the 24 th month after surgery ( t=5.45 to 9.39, all P<0.01). Compared with the preoperative period, the velocity of portal vein blood from the first week after surgery to the 24 th month after surgery was decreased ( t=4.02 to 8.43, all P<0.01). Compared with the preoperative period, routine blood parameters (white blood count, hemoglobin, platelet count), liver function (total bilirubin, albumin, prothrombin time, international normalized ratio, Child-Pugh score), liver synthetic protein (AT-Ⅲ, protein S, protein C) and liver fibrotic markers (collagen type Ⅳ, procollagen type Ⅲ, laminin, hyaluronidase) were improved to varying degrees at the 24th month after surgery ( t=-20.46 to 11.93, all P<0.01). Conclusion:Preliminary findings show that LSD can reduce portal vein pressure, restore blood cell number, and improve liver synthesis function and the degree of liver fibrosis in patients with portal hypertension in liver cirrhosis.

ObjectiveTo investigate the mechanism of Shenkang injection in delaying diabetic kidney disease by regulating endoplasmic reticulum stress and attenuating podocyte apoptosis through the Glucose regulated protein 78 （ GRP78 ） / transcription factor C / EBP homologous protein （ CHOP ） signaling pathway （GRP78/CHOP） signaling pathway. MethodsFor the animal experiment， 10 12-week-old db/m mice were selected as a normal group， and 30 12-week-old db/db mice were randomly divided into a model group， a Shenkang injection group （15.6 mL·kg^-1）， and a dapagliflozin group （1.6 mg·kg^-1）. To observe the general condition of mice， fasting blood glucose， urinary albumin/urine creatinine （ACR）， and 24 h urine protein quantification were detected in each group before drug administration. After 12 weeks of drug treatment， mice were tested for fasting blood glucose， total cholesterol （TC）， triglyceride （TG）， low-density cholesterol （LDL）， ACR， 24 h urine protein quantification， blood creatinine （SCr）， and blood urea （UREA）. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy were used to observe the pathologic morphology in renal tissue. Immunohistochemistry was used to detect the expressions of nephroprotective marker protein （Nephrin）， glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in renal tissue. Western blot was used to detect the expressions of GRP78， CHOP， Bcl-2， Bax， and Nephrin proteins， and Real-time polymerase chain reaction （Real-time PCR） was employed to detect the expressions of Nephrin， GRP78， CHOP， Bcl-2， and Bax mRNAs in renal tissue. ResultsBefore drug administration， compared with those in the normal group， the body mass of db/db mice was significantly increased， and blood glucose， 24 h urine protein quantification， and ACR were significantly elevated in the Shenkang injection group and Dapagliflozin group （P<0.01）. After 12 weeks of administration， compared with those in the model group， the general state of mice in the Shenkang injection group was significantly improved， and the body mass was decreased. The blood glucose was significantly reduced （P<0.01）， and blood lipids TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）. The 24 h urine protein quantification and ACR were significantly decreased （P<0.05）， and SCr and UREA were significantly reduced （P<0.01）. Compared with those of the model group， the pathologic results of the Shenkang injection group showed that proliferation of mesangial cells， reduction of inflammatory cell infiltration， and alleviation of renal tubular vacuolization and podocyte damage were observed in renal tissue of mice. Electron microscopy showed that fusion of the pedicle protruding and thickening of the basement membrane were reduced. Immunohistochemistry results showed that the expressions of GRP78， CHOP， and Bax proteins were significantly reduced （P<0.01）， and the expressions of Nephrin and Bcl-2 proteins were significantly increased （P<0.01） in renal tissue of the Shenkang injection group. Western blot results showed that the expressions of Nephrin and Bcl-2 in the Shenkang injection group were significantly increased （P<0.05， P<0.01）， and the expressions of GRP78， CHOP， and Bax proteins were significantly decreased （P<0.05， P<0.01）. Real-time PCR results showed that the expressions of GRP78， CHOP， and Bax mRNAs were down regulated in the Shenkang injection group （P<0.01）， and the expressions of Nephrin and Bcl-2 mRNAs were up regulated （P<0.01）. ConclusionShenkang injection inhibits endoplasmic reticulum stress response and podocyte apoptosis by regulating the GRP78/CHOP signaling pathway， which in turn ensures the integrity of glomerular filtration barrier， reduces the occurrence of proteinuria， improves renal function， and thus delays the progression of diabetic kidney disease.

ObjectiveTo investigate the mechanism of Shenkang injection in delaying diabetic kidney disease by regulating endoplasmic reticulum stress and attenuating podocyte apoptosis through the Glucose regulated protein 78 （ GRP78 ） / transcription factor C / EBP homologous protein （ CHOP ） signaling pathway （GRP78/CHOP） signaling pathway. MethodsFor the animal experiment， 10 12-week-old db/m mice were selected as a normal group， and 30 12-week-old db/db mice were randomly divided into a model group， a Shenkang injection group （15.6 mL·kg^-1）， and a dapagliflozin group （1.6 mg·kg^-1）. To observe the general condition of mice， fasting blood glucose， urinary albumin/urine creatinine （ACR）， and 24 h urine protein quantification were detected in each group before drug administration. After 12 weeks of drug treatment， mice were tested for fasting blood glucose， total cholesterol （TC）， triglyceride （TG）， low-density cholesterol （LDL）， ACR， 24 h urine protein quantification， blood creatinine （SCr）， and blood urea （UREA）. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy were used to observe the pathologic morphology in renal tissue. Immunohistochemistry was used to detect the expressions of nephroprotective marker protein （Nephrin）， glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in renal tissue. Western blot was used to detect the expressions of GRP78， CHOP， Bcl-2， Bax， and Nephrin proteins， and Real-time polymerase chain reaction （Real-time PCR） was employed to detect the expressions of Nephrin， GRP78， CHOP， Bcl-2， and Bax mRNAs in renal tissue. ResultsBefore drug administration， compared with those in the normal group， the body mass of db/db mice was significantly increased， and blood glucose， 24 h urine protein quantification， and ACR were significantly elevated in the Shenkang injection group and Dapagliflozin group （P<0.01）. After 12 weeks of administration， compared with those in the model group， the general state of mice in the Shenkang injection group was significantly improved， and the body mass was decreased. The blood glucose was significantly reduced （P<0.01）， and blood lipids TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）. The 24 h urine protein quantification and ACR were significantly decreased （P<0.05）， and SCr and UREA were significantly reduced （P<0.01）. Compared with those of the model group， the pathologic results of the Shenkang injection group showed that proliferation of mesangial cells， reduction of inflammatory cell infiltration， and alleviation of renal tubular vacuolization and podocyte damage were observed in renal tissue of mice. Electron microscopy showed that fusion of the pedicle protruding and thickening of the basement membrane were reduced. Immunohistochemistry results showed that the expressions of GRP78， CHOP， and Bax proteins were significantly reduced （P<0.01）， and the expressions of Nephrin and Bcl-2 proteins were significantly increased （P<0.01） in renal tissue of the Shenkang injection group. Western blot results showed that the expressions of Nephrin and Bcl-2 in the Shenkang injection group were significantly increased （P<0.05， P<0.01）， and the expressions of GRP78， CHOP， and Bax proteins were significantly decreased （P<0.05， P<0.01）. Real-time PCR results showed that the expressions of GRP78， CHOP， and Bax mRNAs were down regulated in the Shenkang injection group （P<0.01）， and the expressions of Nephrin and Bcl-2 mRNAs were up regulated （P<0.01）. ConclusionShenkang injection inhibits endoplasmic reticulum stress response and podocyte apoptosis by regulating the GRP78/CHOP signaling pathway， which in turn ensures the integrity of glomerular filtration barrier， reduces the occurrence of proteinuria， improves renal function， and thus delays the progression of diabetic kidney disease.

Objective: To investigate the clinical efficacy and safety of pudendal nerve modulation (PNM) in the treatment of female pudendal neuralgia (PN)，so as to promote the clinical application of this technique. Methods: A retrospective analysis was conducted on 20 female PN patients who failed conservative treatment at Gongli Hospital during Nov.2020 and Oct.2023.All patients underwent simultaneous PNM and sacral nerve modulation (SNM) with the assistance of 3D printing navigation.Dual-stage test electrodes for PNM and SNM were implanted，followed by alternate therapeutic trial for each modality.Secondary conversion rates and longitudinal outcomes，including visual analogue score (VAS)，patient health questionnaire-9 (PHQ-9)，and quality of life (QoL) scores were compared preoperatively，post-stage Ⅰ，and at 3，6，and 12 months post-stage Ⅱ. Results: All operations were successful.After the trial phase，the secondary conversion rate for PNM was significantly higher than that for SNM; 16 patients (16/20，80%) chose the second-phase PNM implantation surgery，3 (3/20，15%) chose second-phase SNM implantation，and 1 (1/20，5%) had electrodes removed due to ineffective results from both trials.Further assessment revealed that the improvements in VAS，PHQ-9，and QoL scores for PNM patients were significantly better than those for SNM patients after the first phase of surgery and at 3，6 and 12 months after the second-phase conversion (P<0.05).No complications such as electrode migration or infection were observed during the follow-up of 12-15 months. Conclusion: PNM provides more effective relief of pain symptoms and improvements in depressive states for female PN patients compared to SNM.With the assistance of 3D printing navigation，the operation is simple and safe，and offers stable therapeutic effects.It is worthy of clinical promotion and application.

OBJECTIVE: To observe the clinical efficacy of Qihuang needle therapy for autism spectrum disorder (ASD) children with sleep disorder. METHODS: A total of 60 ASD children with sleep disorder were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with structured education intervention, 60 min each time, once a day, 6 times a week. Qihuang needle therapy was applied at Yintang (GV24⁺), Baihui (GV20) and bilateral Jueyinshu (BL14), Xinshu (BL15) in the observation group, multi-direction needling was delivered and without needle retaining. The treatment was given 2 times a week, each treatment was delivered at interval of 2 days at least. Behavioral intervention was adopted in the control group. Treatment for consecutive 12 weeks was required in both groups. Before and after treatment, the scores of children's sleep habits questionnaire (CSHQ), the autism behavior checklist (ABC), the childhood autism rating scale (CARS), and the childhood autism behavior scale (CABS) were observed in the two groups. RESULTS: After treatment, the scores of CSHQ, ABC, CARS and CABS were decreased compared with those before treatment (P<0.01), and the above scores in the observation group were lower than those in the control group (P<0.05). CONCLUSION Qihuang needle therapy can effectively treat ASD with sleep disorder, improve the core symptoms of ASD and the sleep quality.
Humans ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Child ; Sleep Wake Disorders/physiopathology* ; Child, Preschool ; Acupuncture Therapy ; Acupuncture Points ; Treatment Outcome ; Sleep ; Needles

(+)-Borneol, the main component of "Natural Borneol" in the Chinese Pharmacopoeia, is a high-end spice and precious medicine. Plant extraction cannot meet the increasing demand for (+)-borneol, while microbial biosynthesis offers a sustainable supply route. However, its production was extremely low compared with other monoterpenes, even with extensively optimizing the mevalonate pathway. We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate (BPP), which suffers the side-reaction and the competition from the cellular dephosphorylation process, especially lipid metabolism, thus limiting (+)-borneol synthesis. Here, we systematically optimized the dephosphorylation process by identifying, characterizing phosphatases, and balancing cellular dephosphorylation metabolism. For the first time, we identified two endogenous phosphatases and seven heterologous phosphatases, which significantly increased (+)-borneol production by up to 152%. By engineering BPP dephosphorylation and optimizing the MVA pathway, the production of (+)-borneol was increased by 33.8-fold, which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks, so far the highest reported in the literature. This study showed that rewiring dephosphorylation metabolism was essential for high-level production of (+)-borneol in Saccharomyces cerevisiae, and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Objective:To analyze the trend of colorectal cancer incidence and age changes in cancer registration areas of Jiangsu Province from 2009 to 2019.Methods:Based on the continuous and complete data of 16 cancer registries with qualified quality control in Jiangsu Province from 2009 to 2019, the crude incidence rate, age-standardized incidence rate by Segi World Standard Population (ASIRW), age-specific incidence rate, mean age at onset, standardized mean age at onset, standardized age-specific incidence proportion, and incidence proportion of the population over 60 years old of colorectal cancer were calculated. Joinpoint software was used to calculate the average annual percentage change (AAPC) of crude incidence rate, ASIRW, age-specific incidence rate, and incidence proportion of the population over 60 years, respectively. Birth cohort models were constructed to analyze the incidence of colorectal cancer and its trends in the population born from 1929 to 2019. Linear regression models were used to analyze the correlation between mean age at onset, standardized mean age at onset and the year of onset.Results:From 2009 to 2019, a total of 48 036 new cases of colorectal cancer were collected from 16 cancer registries in Jiangsu Province, including 27 508 males and 20 528 females. The crude incidence rate and ASIRW of colorectal cancer in Jiangsu Province increased from 19.00/100 000 and 12.32/100 000 in 2009 to 33.49/100 000 and 16.75/100 000 in 2019, respectively, showing a significant upward trend (CR: AAPC=5.99%, ASIRW: AAPC=3.54%, P<0.001). The increase of ASIRW was greater in males than that observed in females (males: AAPC=4.31%, females: AAPC=2.34%, P<0.001), and greater in rural areas than in urban areas (rural areas: AAPC=4.03%, urban areas: AAPC=3.13%, P<0.001). The incidence of people over 50 years old increased significantly by year, with the 60~69 age group exhibiting a more rapid increase ( AAPC=4.97%, P<0.05). In the birth cohort, the incidence increased rapidly in the population over 50 years with the passage of birth year, with AAPCs ranging from 1.76% to 7.05% ( P<0.05). From 2009 to 2019, the standardized mean age at onset of colorectal cancer increased by 0.10 years annually. The proportion of standardized age-specific incidence exhibited a trend of increase in older age groups, and the incidence proportion of the population over 60 years old showed a significant yearly increase ( AAPC=0.86%, P<0.001). Conclusion:From 2009 to 2019, the incidence, mean age at onset and the incidence proportion of the population over 60 years old of colorectal cancer in Jiangsu Province could exhibit a rapid upward trend. The increase is particularly pronounced in males and rural areas. Additionally, the age-specific incidence distribution reveals a trend of increase in older age groups. Therefore, targeted adjustments and comprehensive prevention measures should be strengthened.