Objective To study the bioequivalence and safety of two olmesartan medoxomil and hydrochlorothiazide tablets in Chinese healthy subjects.Methods A total of 24 healthy subjects underwent fasting and postprandial tests in a single-center,randomized,open-label,single-dose,two-formulation,two-sequence,two-period,self-cross-over controlled design.The subjects were administered a single oral dose of the test formulation and reference formulation(each containingolmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg)in a random cross-over fashion.The plasma concentrations of olmesartan and hydrochlorothiazide were determined by LC-MS/MS.The non-compartmental model analysis of olmesartan and hydrochlorothiazide was conducted using WinNonlin 7.0 software to calculate pharmacokinetic parameters and assess bioequivalence.Results In the fasting test,the pharmacokinetic parameters of olmesartan of test and reference were as follows:Cmax were(798.35±206.78)and(664.52±168.25)ng·mL-1,AUC0-t were(4 430.71±1 294.87)and(3 976.67±1 083.54)h·ng·mL-1,AUC0-∞ were(4 551.67±1 303.06)and(4 090.37±1 103.97)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(92.39±35.96)and(96.15±38.76)ng·mL-1,AUC0_t were(548.69±217.11)and(564.41±208.68)h·ng·mL-1,AUC0-∞ were(603.04±228.59)and(619.26±223.27)h·ng·mL-1.In the fed test,the pharmacokinetic parameters of olmesartan of T and R were as follows:Cmax were(583.15±149.48)and(550.57±104.76)ng·mL-1,AUC0-t were(3 585.18±952.72)and(3 292.19±904.58)h·ng·mL-1,AUC0-∞ were(3 696.05±996.55)and(3 396.30±923.41)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(70.30±17.88)and(74.70±21.65)ng·mL-1,AUC0-t were(476.60±119.39)and(492.91±144.81)h·ng·mL-1,AUC0-∞ were(523.37±132.67)and(535.81±151.92)h·ng·mL-1.In fasting and fed condition,the 90％confidence interval(90％CI)of Cmax,AUC0-t and AUC0-∞ of olmesartan and hydrochlorothiazide were in 80.00％-125.00％.Conclusion The two olmesartan medoxomil and hydrochlorothiazide tablets were bioequivalent under fasting and fed conditions,and good security.

This study collected epidemic data of COVID-19 in Zhengzhou from January 1 to January 20 in 2022. The epidemiological characteristics of the local epidemic in Zhengzhou High-tech Zone caused by the SARS-CoV-2 Delta variant were analyzed through epidemiological survey and big data analysis, which could provide a scientific basis for the prevention and control of the Delta variant. In detail, a total of 276 close contacts and 599 secondary close contacts were found in this study. The attack rate of close contacts and secondary close contacts was 5.43% (15/276) and 0.17% (1/599), respectively. There were 10 confirmed cases associated with the chain of transmission. Among them, the attack rates in close contacts of the first, second, third, fourth and fifth generation cases were 20.00% (5/25), 17.86% (5/28), 0.72% (1/139) and 14.81% (4/27), 0 (0/57), respectively. The attack rates in close contacts after sharing rooms/beds, having meals, having neighbor contacts, sharing vehicles with the patients, having same space contacts, and having work contacts were 26.67%, 9.10%, 8.33%, 4.55%, 1.43%, and 0 respectively. Collectively, the local epidemic situation in Zhengzhou High-tech Zone has an obvious family cluster. Prevention and control work should focus on decreasing family clusters of cases and community transmission.
Humans ; SARS-CoV-2 ; COVID-19 ; Epidemics ; Incidence

Objective:To investigate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with maintenance hemodialysis (MHD) in Jiangsu province during SARS-CoV-2 pandemic in China from December 7, 2022 to January 27, 2023, and to analyze the influencing factors of all-cause death.Methods:It was a multi-center cross-sectional investigation. Structured questionnaire was used to collect patient information by medical staff of each hemodialysis center (room) as investigators. Part of the demography data and laboratory examination data came from the Jiangsu Province Hemodialysis Data Information System. MHD patients from hemodialysis centers (rooms) at all levels of medical institutions and independent hemodialysis institutions in Jiangsu province during the outbreak of SARS-CoV-2 infection were included, and the clinical characteristics and all-cause mortality of confirmed and suspected cases of SARS-CoV-2 infection were analyzed.Results:Questionnaire surveys and data analysis on 57 278 patients in 407 hemodialysis centers (rooms) were completed, accounting for 90.41% of the total number of MHD patients (63 357 cases) in Jiangsu province during the same period. There were 24 038 cases (41.97%) of SARS-CoV-2 infection and 14 805 cases (25.85%) of suspected infection, which were widely distributed in all dialysis centers in Jiangsu province. After clinical classification of 38 843 confirmed and suspected SARS-CoV-2 infection cases, 3 662 cases were severe and critical cases, accounting for 9.43% of the infected and suspected cases. Among the patients who had completed the questionnaires, there were 1 812 all-cause deaths, with an all-cause mortality rate of 3.16%. Multivariate logistic regression analysis showed that elderly (taking ≤50 years as a reference, 51-59 years: OR=1.583, 95% CI 1.279-1.933, P=0.001; 60-69 years: OR=3.972, 95% CI 3.271-4.858, P<0.001; 70-79 years: OR=7.236, 95% CI 5.917-8.698, P<0.001; ≥80 years: OR=11.738, 95% CI 9.459-14.663, P<0.001), male ( OR=1.371, 95% CI 1.229-1.529, P<0.001), and co-infection with hepatitis B virus (HBV) (positive serum HBV surface antigen, OR=0.629, 95% CI 0.484-0.817, P<0.001) were independent influencing factors for all cause mortality. Receiver-operating characteristic curve analysis showed that the area under the curve for male, age and current HBV infection prediction of all-cause death was 0.529 ( P<0.001), 0.724 ( P<0.001) and 0.514 ( P=0.042), respectively, and the cut-off value for age prediction of all-cause death was 65.5 years old. Compared with patients without HBV infection, MHD patients with HBV infection significantly reduced the proportion of severe and critically ill patients, all-cause hospitalizations and all cause deaths when infected with SARS-CoV-2 (4.99% vs. 6.41%, χ2=6.136, P=0.013; 8.90% vs. 11.44%, χ2=11.662, P<0.001; 2.01% vs. 3.37%, χ2=10.713, P=0.001, respectively). Conclusion:The MHD patients in Jiangsu province are susceptible to SARS-CoV-2. Elderly age and male gender are independent risk factors for death in MHD patients during the epidemic, while the HBV infection may be a protective factor for death of MHD patients infected with SARS-CoV-2.

OBJECTIVE: To investigate the outcome of lateral femoral notch (LFN) after early anterior cruciate ligament (ACL) reconstruction and evaluate the recovery of knee joint function after the operation. METHODS: The clinical data of 32 patients who underwent early ACL reconstruction from December 2015 to December 2019 were retrospectively analyzed. The study included 18 males and 14 females, aged 16 to 54 years old, with an average age of (25.39±2.82) years. The body mass index (BMI) of the patients ranged from 20 to 30 kg/cm2, with an average of (26.15±3.09) kg/cm². Among them, 6 cases were caused by traffic accidents, 19 by exercise, and 7 by the crush of heavy objects. MRI of all patients showed LFN depth was more than 1.5 mm after injury, and no intervention for LFN was performed during surgery. Preoperative and postoperative depth, area, and volume of LFN defects were observed by MRI data. International Cartilage Repair Society (ICRS) score, Lysholm score, Tegner activity levels, and knee injury and osteoarthritis outcome score (KOOS) were analyzed before and after the operation. RESULTS: All patients were followed up from 2 to 6 years with an average of (3.28±1.12) years. There was no significant difference in the defect depth of LFN from (2.31±0.67) mm before the operation to (2.53±0.50) mm at follow-up (P=0.136). The defect area of LFN was decreased from (207.55±81.01)mm² to (171.36±52.69)mm² (P=0.038), and the defect volume of LFN was decreased from (426.32±176.54) mm³ to (340.86±151.54)mm³ (P=0.042). The ICRS score increased from (1.51±0.34) to (2.92±0.33) (P<0.001), the Lysholm score increased from (35.37±10.54) to (94.46±8.45) (P<0.001), and the Tegner motor score increased from (3.45±0.94) to (7.56±1.28), which was significantly higher than that of the preoperative data (P<0.001). The KOOS score of the final follow-up was 90.42±16.35. CONCLUSION With the increase of recovery time after anterior cruciate ligament reconstruction, the defect area and volume of LFN decreased gradually, but the defect depth remained unchanged. The knee joint function of the patients significantly improved. The cartilage of the LFN defect improved, but the repair effect was not good.
Male ; Female ; Humans ; Young Adult ; Adult ; Adolescent ; Middle Aged ; Anterior Cruciate Ligament Injuries/surgery* ; Retrospective Studies ; Magnetic Resonance Imaging ; Anterior Cruciate Ligament Reconstruction ; Femur/surgery* ; Treatment Outcome ; Knee Joint/surgery*

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ² test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 9^th to <10^th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ²=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ²=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ²=1.878, P=0.171; χ²=0.078, P=0.780; χ²=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

Objective: To explore the value of cerebral hypoxic-ischemic injury markers in the early diagnosis of sepsis associated encephalopathy (SAE) in burn patients with sepsis. Methods: A retrospective case series study was conducted. From October 2018 to May 2021, 41 burn patients with sepsis who were admitted to Zhengzhou First People's Hospital met the inclusion criteria, including 23 males and 18 females, aged 18-65 (35±3) years. According to whether SAE occurred during hospitalization, the patients were divided into SAE group (21 cases) and non-SAE group (20 cases). The gender, age, deep partial-thickness burn area, full-thickness burn area, and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores of patients were compared between the two groups. The serum levels of central nervous system specific protein S100β and neuron specific enolase (NSE) at 12, 24, and 48 h after sepsis diagnosis (hereinafter referred to as after diagnosis), the serum levels of interleukin-6 (IL-6), IL-10, tumor necrosis factor α (TNF-α), Tau protein, adrenocorticotropic hormone (ACTH), and cortisol at 12, 24, 48, 72, 120, and 168 h after diagnosis, and the mean blood flow velocity of middle cerebral artery (VmMCA), pulsatility index, and cerebral blood flow index (CBFi) on 1, 3, and 7 d after diagnosis of patients in the two groups were counted. Data were statistically analyzed with chi-square test, analysis of variance for repeated measurement, independent sample t test, and Bonferroni correction. The independent variables to predict the occurrence of SAE was screened by multi-factor logistic regression analysis. The receiver operating characteristic (ROC) curve was drawn for predicting the occurrence of SAE in burn patients with sepsis, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. Results: The gender, age, deep partial-thickness burn area, full-thickness burn area, and APACHE Ⅱ score of patients in the two groups were all similar (χ²=0.02, with t values of 0.71, 1.59, 0.91, and 1.07, respectively, P>0.05). At 12, 24, and 48 h after diagnosis, the serum levels of S100β and NSE of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 37.74, 77.84, 44.16, 22.51, 38.76, and 29.31, respectively, P<0.01). At 12, 24, 48, 72, 120, and 168 h after diagnosis, the serum levels of IL-10, Tau protein, and ACTH of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 10.68, 13.50, 10.59, 8.09, 7.17, 4.71, 5.51, 3.20, 3.61, 3.58, 3.28, 4.21, 5.91, 5.66, 4.98, 4.69, 4.78, and 2.97, respectively, P<0.01). At 12, 24, 48, 72, and 120 h after diagnosis, the serum levels of IL-6 and TNF-α of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 8.56, 7.32, 2.08, 2.53, 3.37, 4.44, 5.36, 5.35, 6.85, and 5.15, respectively, P<0.05 or P<0.01). At 12, 24, and 48 h after diagnosis, the serum level of cortisol of patients in SAE group was significantly higher than that in non-SAE group (with t values of 5.44, 5.46, and 3.55, respectively, P<0.01). On 1 d after diagnosis, the VmMCA and CBFi of patients in SAE group were significantly lower than those in non-SAE group (with t values of 2.94 and 2.67, respectively, P<0.05). On 1, 3, and 7 d after diagnosis, the pulsatile index of patients in SAE group was significantly higher than that in non-SAE group (with t values of 2.56, 3.20, and 3.12, respectively, P<0.05 or P<0.01). Serum IL-6 at 12 h after diagnosis, serum Tau protein at 24 h after diagnosis, serum ACTH at 24 h after diagnosis, and serum cortisol at 24 h after diagnosis were the independent risk factors for SAE complicated in burn patients with sepsis (with odds ratios of 2.42, 1.38, 4.29, and 4.19, 95% confidence interval of 1.76-3.82, 1.06-2.45, 1.37-6.68, and 3.32-8.79, respectively, P<0.01). For 41 burn patients with sepsis, the AUC of ROC of serum IL-6 at 12 h after diagnosis for predicting SAE was 0.92 (95% confidence interval was 0.84-1.00), the best threshold was 157 pg/mL, the sensitivity was 81%, and the specificity was 89%. The AUC of ROC of serum Tau protein at 24 h after diagnosis for predicting SAE was 0.92 (95% confidence interval was 0.82-1.00), the best threshold was 6.4 pg/mL, the sensitivity was 97%, and the specificity was 99%. The AUC of ROC of serum ACTH at 24 h after diagnosis for predicting SAE was 0.96 (95% confidence interval was 0.89-1.00), the best threshold was 14.7 pg/mL, the sensitivity was 90%, and the specificity was 94%. The AUC of ROC of serum cortisol at 24 h after diagnosis for predicting SAE was 0.93 (95% confidence interval was 0.86-1.00), the best threshold was 89 nmol/L, the sensitivity was 94%, and the specificity was 97%. Conclusions: Serum Tau protein, ACTH, and cortisol have high clinical diagnostic value for SAE complicated in burn patients with sepsis.
Adolescent ; Adult ; Aged ; Burns/complications* ; Early Diagnosis ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; ROC Curve ; Retrospective Studies ; Sepsis/diagnosis* ; Sepsis-Associated Encephalopathy ; Young Adult

The recycling of traditional Chinese medicine （TCM） wastes is an important research topic to be solved urgently in the industrialization of TCM resources. Rhei Radix et Rhizoma is a bulk Chinese herb mainly derived from Rheum palmatum，R. tanguticum，and R. officinale. At present，these three medicinal plants have been cultivated on a large scale and widely used in the fields of medicine，health care，food，cosmetics，and veterinary medicine，with an annual demand of more than 5 500 tons（1 ton=1 000 kg）. However，a large number of wastes such as non-medicinal parts and residues produced in the production and deep processing are discarded because there is no effective way of utilization，resulting in serious waste of resources and environmental pollution. The non-medicinal parts contain not only the chemical components and pharmacological effects similar to those of roots and rhizomes but also a variety of amino acids，mineral elements，and conventional nutrients. They have a long history of use，and the content of some resource components is higher than that in roots and rhizomes. In particular，their stems and leaves exhibit great potential to be consumed as food and medicine due to high safety. Besides，the content of anthraquinones in Rhei Radix et Rhizoma residue is high and it possesses good antibacterial activity. It can be seen that the waste from the industrialization of Rhei Radix et Rhizoma has high utilization value. Hence，based on the relevant literature and investigation on the application of producing areas in China and abroad，the paper summarized the utilization status of their medicinal and non-medicinal parts，the waste production in the industrialization，as well as the active substances and utilization ways and put forward the multi-level and multi-path utilization strategy of Rhei Radix et Rhizoma wastes，in order to provide reference for the rational development and application of Rhei Radix et Rhizoma resources and promote the effective utilization and green development of the corresponding wastes.

Objective: To observe the effect of acupoint massage plus Vitalstim electrical stimulation on deglutition function and surface electromyography (SEMG) of deglutition muscle groups. Methods: A total of 60 patients with deglutition disorder after stroke were selected and divided into an electrical stimulation group, a massage group and an integrated group according to the random number table method, with 20 cases in each group. Patients in these three groups were given the same routine rehabilitation training for deglutition. In addition, patients in the electrical stimulation group were given extra Vitalstim electrical stimulation, patients in the massage group were given extra acupoint massage on the head, face and neck, and patients in the integrated group were given extra acupoint massage plus Vitalstim electrical stimulation. Fujishima Ichiro food intake level scale (FILS) was scored before and after treatment. The swallowing duration and maximal amplitude of masseter muscle in SEMG were evaluated before and after treatment. Results: After treatment, the FILS score and the maximal amplitude of recruitment potential generated by muscular contraction of masseter muscle group in the three groups were higher than those before treatment (all P<0.05), and the swallowing duration of masseter muscle group was shortened compared with that in the same group before treatment (all P<0.05). After treatment, the FILS score in the integrated group was higher than that in the electrical stimulation group and the massage group (both P<0.05). The swallowing duration of masseter muscle group measured by SEMG was lower than that in the electrical stimulation group and the massage group (both P<0.05), while the maximal amplitude was higher than that of the electrical stimulation group and the massage group (P<0.05). After treatment, there were no significant differences in the FILS score, swallowing duration and maximal amplitude of masseter muscle group between the electrical stimulation group and the massage group (all P>0.05). Conclusion: Both acupoint massage and electrical stimulation can improve the deglutition function in patients with deglutition disorder after stroke, and improve the coordination and flexibility of masseter muscle. The integration of the two is more effective.

Objective: To explore the protective effect and the preliminary mechanism of Dihuang Yinzi on cerebral ischemia-reperfusion injury in rats. Method: The middle cerebral artery occlusion (MCAO) model was established. Totally 90 SD rats were randomly divided into 6 groups:sham operation group, model group, nimodipine group (0.01 g·kg^-1) and high, medium, low-dose Dihuang Yinzi groups (38.80, 19.40, 9.70 g·kg^-1), with 20 rats in each group.The modified neurological severity score (mNSS) was assayed at the 7^th, 14^th, 28^th days after operation, and the volume of cerebral infarction, pathological changes of brain tissue, the BrdU positive cells and mRNA levels of Notch1, Jagged1 and Hes1 in subventricular zone(SVZ)were observed respectively by triphenyl tetrazolium chloride(TTC) stain, htorylin eastin(HE) stain, immunofluorescence technique and reverse transcriphase polymerase chain reaction(Real-time PCR) methods at the 28^th day after the operation. Result: The mNSS on the 7^th, 14^th, 28^th days of high, medium-dose Dihuang Yinzi groups and nimodipine group were significantly lower than that of model group(P<0.05, P<0.01). On the 28^th day, the percentage of cerebral infarction volume in brain tissue volume of high, medium-dose Dihuang Yinzi groups and nimodipine group were smaller than that of model group(P<0.01).HE staining showed that the necrosis and softening lesions of brain tissue were not obvious in rats of high, medium-dose Dihuang Yinzi groups and nimodipine group, with neuronal cell and neuroglial cell proliferation. On the 28^th day, the BrdU positive cells in SVZ of the above 3 groups were significantly higher than model group(P<0.05, P<0.01), and the high-dose Dihuang Yinzi group was significantly higher than nimodipine group(P<0.05). On the 28^th day, the mRNA levels of Notch1, Jagged1 and Hes1 of high, medium-dose Dihuang Yinzi groups and nimodipine group were significantly higher than those of model group(P<0.05, P<0.01), the mRNA level of Hes1 of nimodipine group was higher than that of high, medium, low-dose Dihuang Yinzi groups(P<0.05, P<0.01). Conclusion: Dihuang Yinzi can improve the nerve function defect of MCAO rat model, and reduce the volume of cerebral infarction and the pathological changes of brain tissue, thus playing a protective role in cerebral ischemia-reperfusion injury rats. Its mechanism may be related to the activation of the Notch signaling pathway, and the up-regulation of expressions of Notch1, Jagged1 and Hes1 mRNA, thus promoting the proliferation of NSCs.

At present, lung cancer ranks second and first respectively in the incidence and the mortality among malignant tumors. It is urgent to find new effective anti-lung cancer drugs with less side effects and relatively defined mechanisms. Endoplasmic reticulum stress (ERS)-mediated apoptosis pathway is an effective way to promote tumor cell apoptosis; diterpenoid tanshinone (DT), an effective part separated from Salviae Miltiorrhizae Radix et Rhizoma, was found to have an anti-lung cancer effect in previous studies via ERS-induced PERK-EIF2α pathway. In this paper, human lung adenocarcinoma PC9 cell line and nude mouse transplantation tumor model were applied to verify the anti-lung cancer effect of DT in vivo and in vitro, and illuminate the potential mechanism via ERS induced IRE1α/caspase 12 apoptosis pathway. The results showed that in vivo, DT could promote PC9 cell apoptosis in a concentration-dependent manner, up-regulate Bip, IRE1 and TRAF2 protein expressions in tumor tissue, reduce tumor weight and alleviate bodyweight loss. In vitro, DT inhibited the proliferation of PC9 cell line in a concentration-dependent manner, and destroyed the structure of mitochondria in PC9 cell, promoted Bax, IRE1α, Bip, TRAF2 and caspase 12 protein expressions, lower Bcl-2 protein expression in a time-dependent manner. DT shows a good effect on anti-lung cancer both in vivo and in vitro. The mechanism is related to the activation of ERS-induced IRE1α/caspase 12 apoptosis pathway and the promotion of cell apoptosis. ERS-mediated apoptosis pathway may be an important target of DT on anti-lung cancer.
Animals ; Apoptosis ; Cell Line, Tumor ; Diterpenes, Abietane ; Endoplasmic Reticulum Stress ; Humans ; Lung Neoplasms ; Mice ; Signal Transduction