ObjectiveTo investigate the mechanisms of mitochondrial dynamics and metabolic reprogramming in the treatment of diabetic nephropathy （DN） by Shenxiao Tongluo prescription via the peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/sirtuin-3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α） signaling pathway. MethodsSixty-five SD rats were randomized into a sham group （10 rats） and a modeling group （55 rats）， and the modeling rats underwent left nephrectomy and intraperitoneal injection of streptozotocin （35 mg·kg^-1） to prepare a DN model. After successful modeling， the rats were randomized into model， empagliflozin （10 mg·kg^-1）， and low-， medium-， and high-dose （7.656， 15.312， 30.624 g·kg^-1， respectively） Shenxiao Tongluo prescription groups. The urine microalbumin （UmAlb）， blood urea nitrogen （BUN）， and serum creatinine （SCr） levels of rats in each group were assessed after continuous gavage for 8 weeks. The corresponding kits were used to measure the levels of lactate， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the kidney tissue. Hematoxylin-eosin staining， Masson staining， and periodic acid-Schiff staining were performed to observe the pathological changes in the kidney tissue. Transmission electron microscopy was employed to observe mitochondrial morphology. Immunohistochemistry was employed to determine the expression levels of dynamin-related protein 1 （DRP1） and pyruvate kinase M2 （PKM2） in the kidney tissue. Western blot was adopted to assess the protein levels of PGC-1α， SIRT3， HIF-1α， dynamin-related protein 1 （Drp1）， optic atrophy 1 （OPA1）， hexokinase 2 （HK2）， and pyruvate kinase M2 （PKM2） in the kidney tissue. ResultsCompared with the sham group， the model group showed elevated levels of UmAlb， BUN， SCr， lactate， and MDA， decreased SOD level （P<0.05）， glomerular hypertrophy， thickening of the mesangial basement membrane， vacuolar degeneration of renal tubular epithelial cells， and infiltration of renal interstitial inflammatory cells， oval mitochondria with disordered， blurred or disappearing cristae， down-regulated protein levels of PGC-1α， SIRT3， and OPA1， and up-regulated protein levels of HIF-1α， DRP1， HK2， and PKM2 （P<0.05）. Compared with the model group， the treatment in all the groups increased the body weight， lowered the levels of GLU， UmAlb， BUN， and MDA， raised the level of SOD， alleviated the pathological damage in the kidney tissue and mitochondrial damage， up-regulated the expression of PGC-1α， SIRT3， and OPA1， and down-regulated the expression of HIF-1α， DRP1， and PKM2 （P<0.05）. Empagliflozin and Shenxiao Tongluo prescription at medium and high doses lowered the levels of SCr and lactate and down-regulated the expression of HK2 （P<0.05）， which had no statistical significance in the low-dose Shenxiao Tongluo prescription group. ConclusionShenxiao Tongluo prescription may regulate mitochondrial dynamics and metabolic reprogramming by activating the PGC-1α/SIRT3/HIF-1α pathway， thereby alleviating oxidative damage in the kidney tissue and delaying the progression of DN.

ObjectiveTo investigate the mechanisms of mitochondrial dynamics and metabolic reprogramming in the treatment of diabetic nephropathy （DN） by Shenxiao Tongluo prescription via the peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/sirtuin-3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α） signaling pathway. MethodsSixty-five SD rats were randomized into a sham group （10 rats） and a modeling group （55 rats）， and the modeling rats underwent left nephrectomy and intraperitoneal injection of streptozotocin （35 mg·kg^-1） to prepare a DN model. After successful modeling， the rats were randomized into model， empagliflozin （10 mg·kg^-1）， and low-， medium-， and high-dose （7.656， 15.312， 30.624 g·kg^-1， respectively） Shenxiao Tongluo prescription groups. The urine microalbumin （UmAlb）， blood urea nitrogen （BUN）， and serum creatinine （SCr） levels of rats in each group were assessed after continuous gavage for 8 weeks. The corresponding kits were used to measure the levels of lactate， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the kidney tissue. Hematoxylin-eosin staining， Masson staining， and periodic acid-Schiff staining were performed to observe the pathological changes in the kidney tissue. Transmission electron microscopy was employed to observe mitochondrial morphology. Immunohistochemistry was employed to determine the expression levels of dynamin-related protein 1 （DRP1） and pyruvate kinase M2 （PKM2） in the kidney tissue. Western blot was adopted to assess the protein levels of PGC-1α， SIRT3， HIF-1α， dynamin-related protein 1 （Drp1）， optic atrophy 1 （OPA1）， hexokinase 2 （HK2）， and pyruvate kinase M2 （PKM2） in the kidney tissue. ResultsCompared with the sham group， the model group showed elevated levels of UmAlb， BUN， SCr， lactate， and MDA， decreased SOD level （P<0.05）， glomerular hypertrophy， thickening of the mesangial basement membrane， vacuolar degeneration of renal tubular epithelial cells， and infiltration of renal interstitial inflammatory cells， oval mitochondria with disordered， blurred or disappearing cristae， down-regulated protein levels of PGC-1α， SIRT3， and OPA1， and up-regulated protein levels of HIF-1α， DRP1， HK2， and PKM2 （P<0.05）. Compared with the model group， the treatment in all the groups increased the body weight， lowered the levels of GLU， UmAlb， BUN， and MDA， raised the level of SOD， alleviated the pathological damage in the kidney tissue and mitochondrial damage， up-regulated the expression of PGC-1α， SIRT3， and OPA1， and down-regulated the expression of HIF-1α， DRP1， and PKM2 （P<0.05）. Empagliflozin and Shenxiao Tongluo prescription at medium and high doses lowered the levels of SCr and lactate and down-regulated the expression of HK2 （P<0.05）， which had no statistical significance in the low-dose Shenxiao Tongluo prescription group. ConclusionShenxiao Tongluo prescription may regulate mitochondrial dynamics and metabolic reprogramming by activating the PGC-1α/SIRT3/HIF-1α pathway， thereby alleviating oxidative damage in the kidney tissue and delaying the progression of DN.

Recently, there has been an increasing risk of importation of tropical diseases into China and the resultant re-transmission in the country with the in-depth implementation of the “Belt and Road” Initiative, which poses a serious threat to the national public health security. To effectively respond to the cross-border transmission risk of tropical diseases and facilitate the process towards tropical disease control and elimination in China and the countries along the “Belt and Road” Initiative, this article analyzes the current status and governance risks of major imported tropical diseases, cross-border joint prevention and control polices implemented for tropical diseases and challenges in the establishment of the joint prevention and control system for tropical diseases in China, and discusses the establishment and implementation path of the joint prevention and control system for tropical diseases in countries along the “Belt and Road” Initiative. This path covers the establishment of cross-border cooperation mechanisms, research and development and pilot production of Chinese public health products, and implementation of key cross-border tropical disease prevention and control projects. The establishment of this system will further improve Chinese prevention and control capabilities for key cross-border tropical diseases, build a demonstrative prevention and control model for tropical diseases, and promote international technical exchanges and cooperation of tropical diseases.

Objective:To investigate the impact of donor human leukocyte antigen (HLA) -Bw4 expression on natural killer (NK) cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) from maternal or related donors without ex vivo T-cell depletion.Methods:This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors (cohort 1) to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution. Furthermore, a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors (cohort 2) to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes. Thus, a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide (PT-Cy) conditioning.Results:Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery, which remained unaffected by PT-Cy. Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality (TRM), particularly mortality related to infections. The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM.Conclusion:In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion, the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM, especially infection-related mortality. These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT. Hence, the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.

Objective:To investigate the application value of transverse perineal arc incision approach in complete resection of presacral cyst in the lithotomy position.Methods:The retrospec-tive cohort study was conducted. The clinicopathological data of 114 patients who underwent com-plete resection of presacral cyst in Henan Cancer Hospital from August 2012 to October 2021 were collected. There were 14 males and 100 females, aged (35±9)years. All patients were diagnosed as presacral cysts by preoperative magnetic resonance imaging. Of the 114 patients, 76 patients undergoing intraoperative perineal arc incision approach in the lithotomy position were divided into the innovative group, and 38 patients undergoing intraoperative Kraske approach were divided into the traditional group. Observation indicators: (1) surgical situations and specimen; (2) postoperative situations; (3) Follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and com-parison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Surgical situations and specimen. The operation time, volume of intraoperative blood loss, cases with intraoperative combined transabdominal approach or sacrectomy were (137±20)minutes, (261±101)mL, 0 in the innovation group, versus (136±34)minutes, (261±116)mL, 15 in the tradi-tional group, showing no significant difference in the operation time and volume of intraoperative blood loss between the two groups ( t=0.18, 0, P>0.05) and showing a significant difference in cases with intraoperative combined transabdominal approach or sacrectomy between the two groups ( P<0.05). Results of postoperative specimen anatomy in patients of the two groups showed complete removal of the cyst. (2) Postoperative situations. The time to postoperative removing presacral drainage tube, duration of postoperative hospital stay, cases with postoperative second stage healing of incision were (11.4±2.1)days, (13.5±3.5)days, 23 in the innovation group, versus (11.5±1.9)days, (13.7±3.8)days, 4 in the traditional group, showing no significant difference in the time to post-operative removing presacral drainage tube and duration of postoperative hospital stay between the two groups ( t=-0.20, -0.24, P>0.05) and showing a significant difference in cases with postoperative second stage healing of incision between the two groups ( χ2=5.46, P<0.05). Cases with postoperative severe complications were 4 and 2 in the innovation group and the traditional group, respectively, showing no significant difference between the two groups ( P>0.05). (3) Follow-up. All 114 patients were followed up for 48(range, 6?108)months. Cases with recurrence of cysts were 2 and 0 in the innovation group and the traditional group, respectively, showing no significant difference between the two groups ( P>0.05). During the follow-up period, the anal defecation control function of all patients was classified as grade A?B of Williams score. Conclusions:The transverse perineal arc incision approach in complete resection of presacral cyst in the lithotomy position is safe and feasible. Compared with Kraske approach, the transverse perineal arc incision approach in the lithotomy position is more suitable for patients with high presacral cyst.

ObjectiveTo investigate the effect of modified Taohe Chengqitang on NOD-like receptor protein 3 （NLRP3） inflammasome activation in rats with diabetic cardiomyopathy. MethodSPF male SD rats aged 3-4 weeks were randomly divided into a normal group and an experimental group. The rats in the experimental group were fed on a high-fat diet for 4 weeks and then received intraperitoneal injection of streptozotocin （STZ） at 35 mg·kg^-1 to induce the diabetes model. The rats in the experimental group were randomly divided into model group， low- and high-dose modified Taohe Chengqitang groups （11.7 g·kg^-1 and 23.4 g·kg^-1）， and metformin hydrochloride group （67.5 mg·kg^-1） according to the fast blood glucose （FBG）. The cardiac function and structure of rats were detected by ultrasonic imaging after 8 weeks of continuous intragastric administration. Blood samples from the femoral artery were collected to detect FBG， triglyceride （TC）， and total cholesterol （TG） of rats. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in rat myocardium. Serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein expression of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific protease 1 （Caspase-1）， and phosphorylated nuclear factor kappa-B p65 （p-NF-κB p65） in the myocardium was detected by Western blot. ResultCompared with the normal group， the model group showed increased levels of FBG， TC， and TG （P<0.01）， decreased left ventricular ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.05）， myocardial hypertrophy and myocardial fibrosis as revealed by HE staining， increased serum levels of 1L-1β and 1L-18 and protein expression of NLRP3， ASC， Caspase-1， and p-NF-κB p65 in myocardial tissues （P<0.01）. Compared with the model group， the modified Taohe Chengqitang groups and the metformin group showed reduced levels of FBG， TC， and TG （P<0.05）， restored EF and FS （P<0.05）， improved pathological changes in myocardial tissues， and decreased serum levels of IL-1β and IL-18 and protein expression of NLRP3， ASC， Caspase-1， and p-NF-κB p65 in myocardial tissues （P<0.05）. The improvement was more significant in the high-dose modified Taohe Chengqitang group （P<0.05）. ConclusionModified Taohe Chengqitang can protect the myocardium by inhibiting the activation of NLRP3 inflammasomes.

Metabolic regulation has been proven to play a critical role in T cell antitumor immunity. However, cholesterol metabolism as a key component of this regulation remains largely unexplored. Herein, we found that the low-density lipoprotein receptor (LDLR), which has been previously identified as a transporter for cholesterol, plays a pivotal role in regulating CD8

Objective:To evaluate the drug-drug interactions and the tolerability of combined medication between yimitasvir phosphate capsules with sofosbuvir tablets, omeprazole magnesium enteric-coated tablets, and rosuvastatin calcium tablets in healthy volunteers.Methods:A randomized, open, and continuous administration design was used in trial 1 (yimitasvir phosphate capsules with sofosbuvir tablets). 28 subjects were randomly divided into two groups. A non-randomized, open design was used in trial 2 (yimitasvir phosphate capsules with omeprazole magnesium enteric-coated tablets), and included 42 subjects divided into three groups. The open design method was used in trial 3 (yimitasvir phosphate capsules with rosuvastatin calcium tablets), and included 14 subjects. The plasma concentrations of yimitasvir phosphate, sofosbuvir and their main metabolites GS-331007, omeprazole and rosuvastatin were validated by a liquid chromatography/tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated by Phoenix winNonlin software.Results:(1) in trial 1, after single and co-administration, the 90% CI of sofosbuvir C max and AUC 0-tau geometric mean ratio (GMR) were 152.0% (118.0% ~ 197.0%) and 230.0% (184.0% ~ 287.0%), with an increase of 52.0% and 130.0% compared to single dose of sofosbuvir, respectively. The 90% CI of GS-331007 C max GMR was 74.0% (67.5% ~ 81.2%) and reduced by 26% compared to single dose of sofosbuvir. (2) in trial 2, the 90% CI of C max GMR after yimitasvir single or co-administration at the same time, with a 4-hours interval, or with a 12- hours interval were 68.9% (44.5% ~ 106.7%) , 64.0% (43.8% ~ 93.6%) and 56.4%(38.9% ~ 81.9%), and the 90% CI of AUC 0-t GMR were 68.6% (46.5% ~ 101.2%), 68.3% (47.6% ~ 98.0%) and 60.5% (41.8% ~ 87.5%), respectively. Compared with single dose of yimitasvir, the C max and AUC 0-t were decreased by 31.1% and 31.4%, 36.0% and 31.7%, 43.6% and 39.5%, respectively. (3) In trial 3, after single and co-administration, the 90% CI of rosuvastatin C max and AUC 0-72 GMR were 172.4% (153.6% ~ 193.5%) and 158.0% (144.3% ~ 172.9%), respectively, with an increase of 74.9% and 60.5% compared to single dose of rosuvastatin. There were no serious adverse events and adverse events leading to withdrawal from the trial. Conclusion:Yimitasvir phosphate capsules have drug-drug interactions with sofosbuvir tablets, omeprazole magnesium enteric-coated tablets, and rosuvastatin calcium tablets.

Objective:To explore the surgical method and effect of en bloc pelvic resection and anal preservation after radical radiotherapy for cervical cancer.Methods:Clinical data of 20 cervical cancer patients with central recurrence after radical radiotherapy underwent en bloc pelvic resection in the Tumor Hospital of Zhengzhou University and Hainan Provincial People′s Hospital from January 2013 to December 2017 were retrospectively analyzed. The operative time, intraoperative blood loss, length of stay, postoperative anal function and postoperative complications were evaluated.Results:The median operation time of 20 patients with anal preservation after en bloc pelvic resection was 135.2 min, the median intraoperative blood loss was 680 ml, and the median hospitalization time was 16.5 days. Among them, 18 patients had good postoperative healing, and the anal function gradually returned to normal within 6 months after surgery, defecated 1~2 times per day.One patient showed incomplete adhesion between the external colon and the anus. One patient presented with pre-sacral infection. Postoperative pathology confirmed the recurrences in 20 patients, of which 11 cases were squamous cell carcinoma, 7 cases were adenocarcinoma, 2 cases were adenosquamous cell carcinoma.Conclusions:It is safe and reliable to preserve anus after en bloc pelvic resection for cervical cancer patients with radical radiotherapy. The anus function is good enough to improve the postoperative life quality of patients significantly.