ObjectiveTo investigate the mechanism by which Huanglian Jiedutang （HLJDT） inhibits pyroptosis and neuroinflammation in Alzheimer's disease （AD） mice via the NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase）-1/gasdermin D （GSDMD） pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group （model group）， the positive control group （Donepezil group， 0.65 mg·kg^-1）， and the HLJDT treatment group （HLJDT group， 5.2 g·kg^-1）. Ten C57BL/6 mice were assigned to the blank control group （control group）. The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology， quantity， and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 （PSD95）， amyloid precursor protein （APP）， inflammatory factors including nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， as well as pyroptosis pathway-related proteins including NLRP3， Caspase-1， GSDMD， and GSDMD-N. ResultsCompared with the control group， the model group exhibited significantly decreased learning and memory abilities （P<0.01）， reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly increased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.01）. Protein levels of PSD95 were markedly decreased， while the expression levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly elevated （P<0.01）. Compared with the model group， both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities （P<0.05， P<0.01）， increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly decreased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.05， P<0.01）. Protein levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly downregulated， while PSD95 expression was significantly upregulated （P<0.05， P<0.01）. There was no statistically significant difference in GSDMD-N levels in the Donepezil group， while GSDMD-N expression was significantly decreased in the HLJDT group （P<0.05）. ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice， and attenuate neuronal loss and synaptic damage， possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.

ObjectiveTo investigate the mechanism by which Huanglian Jiedutang （HLJDT） inhibits pyroptosis and neuroinflammation in Alzheimer's disease （AD） mice via the NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase）-1/gasdermin D （GSDMD） pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group （model group）， the positive control group （Donepezil group， 0.65 mg·kg^-1）， and the HLJDT treatment group （HLJDT group， 5.2 g·kg^-1）. Ten C57BL/6 mice were assigned to the blank control group （control group）. The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology， quantity， and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 （PSD95）， amyloid precursor protein （APP）， inflammatory factors including nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， as well as pyroptosis pathway-related proteins including NLRP3， Caspase-1， GSDMD， and GSDMD-N. ResultsCompared with the control group， the model group exhibited significantly decreased learning and memory abilities （P<0.01）， reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly increased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.01）. Protein levels of PSD95 were markedly decreased， while the expression levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly elevated （P<0.01）. Compared with the model group， both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities （P<0.05， P<0.01）， increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly decreased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.05， P<0.01）. Protein levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly downregulated， while PSD95 expression was significantly upregulated （P<0.05， P<0.01）. There was no statistically significant difference in GSDMD-N levels in the Donepezil group， while GSDMD-N expression was significantly decreased in the HLJDT group （P<0.05）. ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice， and attenuate neuronal loss and synaptic damage， possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.

Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

Objective:To evaluate the effect of an opioid-sparing anesthesia strategy primarily using quadratus lumborum block combined with esketamine on early postoperative recovery in patients undergoing laparoscopic radical resection of colon cancer.Methods:This study was a randomized controlled trial. From January 2023 to July 2024, 72 patients of either sex, aged 45-65 yr, with body mass index of 18-25 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective laparoscopic radical resection of colon cancer with general anesthesia at Yichang Central People′s Hospital, were divided into 2 groups ( n=36 each) using a random number table method: control group (group C) and opioid-sparing anesthesia strategy group (group D). Anesthesia was induced with sufentanil and propofol and maintained with propofol and remifentanil in group C. In group D, ultrasound-guided quadratus lumborum block was performed before the start of anesthesia, and anesthesia was induced with esketamine, propofol and lidocaine and maintained with esketamine, propofol, low-dose remifentanil, lidocaine and magnesium sulfate. Patient-controlled intravenous analgesia was carried out at the end of surgery until 48 h postoperatively, using dezocine for rescue analgesia. The Quality of Recovery-15 scores were assessed and recorded at 1 day before operation and 1, 3 and 7 days after operation. Ramsay sedation scores were recorded at 2, 6, 12, 24 and 48 h after surgery. The effective pressing times of patient-controlled analgesia and requirement for rescue analgesia were recorded within 24 h after surgery and during the 24-48 h postoperative period. The intraoperative consumption of opioid, emergence time, duration of postanesthesia care unit stay, time to first flatus, first ambulation time and length of postoperative hospital stay were also recorded. The postoperative complications were recorded during hospital stay and assessed with the Clavien-Dindo classification. Results:Compared with group C, the Quality of Recovery-15 scores were significantly increased at each time point after operation, Ramsay sedation scores were increased at 2, 6 and 12 h after operation, the effective pressing times of patient-controlled analgesia and rate of rescue analgesia were decreased in each postoperative period, the intraoperative consumption of remifentanil was reduced, the time to first flatus, first ambulation time and length of postoperative hospital stay were shortened, the incidence of nausea and vomiting was decreased ( P<0.05), and no significant change was found in the emergence time or duration of postanesthesia care unit stay in group D ( P>0.05). Conclusions:The opioid-sparing anesthesia strategy primarily using quadratus lumborum block combined with esketamine can raise the quality of early postoperative recovery in the patients undergoing laparoscopic radical resection of colon cancer.

Objective:To evaluate the effect of an opioid-sparing anesthesia strategy primarily using quadratus lumborum block combined with esketamine on early postoperative recovery in patients undergoing laparoscopic radical resection of colon cancer.Methods:This study was a randomized controlled trial. From January 2023 to July 2024, 72 patients of either sex, aged 45-65 yr, with body mass index of 18-25 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective laparoscopic radical resection of colon cancer with general anesthesia at Yichang Central People′s Hospital, were divided into 2 groups ( n=36 each) using a random number table method: control group (group C) and opioid-sparing anesthesia strategy group (group D). Anesthesia was induced with sufentanil and propofol and maintained with propofol and remifentanil in group C. In group D, ultrasound-guided quadratus lumborum block was performed before the start of anesthesia, and anesthesia was induced with esketamine, propofol and lidocaine and maintained with esketamine, propofol, low-dose remifentanil, lidocaine and magnesium sulfate. Patient-controlled intravenous analgesia was carried out at the end of surgery until 48 h postoperatively, using dezocine for rescue analgesia. The Quality of Recovery-15 scores were assessed and recorded at 1 day before operation and 1, 3 and 7 days after operation. Ramsay sedation scores were recorded at 2, 6, 12, 24 and 48 h after surgery. The effective pressing times of patient-controlled analgesia and requirement for rescue analgesia were recorded within 24 h after surgery and during the 24-48 h postoperative period. The intraoperative consumption of opioid, emergence time, duration of postanesthesia care unit stay, time to first flatus, first ambulation time and length of postoperative hospital stay were also recorded. The postoperative complications were recorded during hospital stay and assessed with the Clavien-Dindo classification. Results:Compared with group C, the Quality of Recovery-15 scores were significantly increased at each time point after operation, Ramsay sedation scores were increased at 2, 6 and 12 h after operation, the effective pressing times of patient-controlled analgesia and rate of rescue analgesia were decreased in each postoperative period, the intraoperative consumption of remifentanil was reduced, the time to first flatus, first ambulation time and length of postoperative hospital stay were shortened, the incidence of nausea and vomiting was decreased ( P<0.05), and no significant change was found in the emergence time or duration of postanesthesia care unit stay in group D ( P>0.05). Conclusions:The opioid-sparing anesthesia strategy primarily using quadratus lumborum block combined with esketamine can raise the quality of early postoperative recovery in the patients undergoing laparoscopic radical resection of colon cancer.

Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

Objective:To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma.Methods:This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of ( M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results:Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ ( P=0.009), hemi-hepatectomy and extended resection ( P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1: OR=1.43 (0.61-3.35), P=0.413;T3 vs. T1: OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions:Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

Objective To explore the effect of opioid-free anesthesia(OFA)combined with quad-ratus lumborum block(QLB)in laparoscopic radical colorectal cancer resection.Methods Sventy patients were selected for undergoing laparoscopic radical colorectal cancer resection from March to December 2023,49 males and 21 females,aged 18-75 years,BM1 18.5-28.0 kg/m2,ASA physical status Ⅱ or Ⅲ.The patients were divided into two groups using random number table method:the OFA group(group OFA)and the conventional opioid anesthesia group(group OA),35 patients in each group.Group OFA underwent bi-lateral posterior QLB under ultrasound guidance before anesthesia induction(0.25％ropivacaine 30 ml on each side),and anesthesia induction and maintenance were performed using opioid-free anesthesia regimen.And group OA cannot undergo QLB,and anesthesia induction and maintenance were carried out using opioid containing regimen.The patient's HR and MAP were recorded before anesthesia induction(T0),1 minute after endotracheal intubation(T1),before pneumoperitoneum establishment(T2),1 minute after pneumo-peritoneum establishment(T3),1 hour after surgery(T4),the end of surgery(T5),and leaving the oper-ating room(T6).The time from the patient's anesthetic discontinuation to extubation,the length of stay in the PACU,and the Steward and VAS pain scores when the patient leaves the operating room,which were recorded.NRS scores at rest and in the motor state 6,12,24,and 48 hours after surgery,time to first ex-haust,time to first ambulation,and length of postoperative hospital stay,effective PCIA pressing times and use of additional analgesic drugs within 48 hours after the operation,and postoperative adverse reactions(nausea,vomiting,hallucinations)were also recorded.Results Compared with T0,the MAP of the two groups decreased significantly at T1,T2,T4,and T5(P＜0.05),the HR in group OFA increased signifi-cantly at T1 and slowed down at T4 and T5(P＜0.05),and the HR in group OA decreased significantly at T1-T5(P＜0.05).Compared with group OA,the HR in group OFA increased significantly at T1-T3,and the MAP increased significantly at T1(P＜0.05).Compared with group OA,the extubation time and PACU residence time were significantly delayed(P＜0.05),and the Steward score when leaving the oper-ating room was significantly lower in group OFA(P＜0.05).Compared with group OA,NRS score was sig-nificantly deceased 6,12,24,and 48 hours after the surgery(P＜0.05),time to first exhaust,time to first ambulation,and length of postoperative hospital stay were significantly shartened(P＜0.05),and ef-fective PCIA pressing times and additional analgesia times were significantly decreased(P＜0.05),inci-dence of intraoperative hypotensionand postoperative nausea and vomiting(P＜0.05).Conclusion OFA combined with QLB can safely and effectively complete laparoscopic radical colorectal cancer surgery.Pa-tients with such anesthetic methods are hemodynamically more stable during anesthesia induction and intrao-peratively.These patients have better postoperative analgesia and less need for additional analgesics,and less incidence of postoperative nausea and vomiting.This approach is more beneficial for the recovery of the patient's gastrointestinal function.

The wide use of crystalline silicon solar cells in the field of new energy is an important boost for China to achieve the environmental protection goal as soon as possible. However, the production and manufacturing processes of these cells give rise to various occupational hazards at workplace, thus posing health risks to workers. This review provided an overview of production processes of crystalline silicon solar cells, the characteristics of occupational health hazards (productive dust; physical factors, productive toxicant) and proposed occupational protection suggestions.

The wide use of crystalline silicon solar cells in the field of new energy is an important boost for China to achieve the environmental protection goal as soon as possible. However, the production and manufacturing processes of these cells give rise to various occupational hazards at workplace, thus posing health risks to workers. This review provided an overview of production processes of crystalline silicon solar cells, the characteristics of occupational health hazards (productive dust; physical factors, productive toxicant) and proposed occupational protection suggestions.