Objective To observe the clinical efficacy of Qigui Tongluo Oral Liquid(a hospital preparation developed by Guangdong Second Traditional Chinese Medicine Hospital and being composed of Astragali Radix,Angelicae Sinensis Radix,Notoginseng Radix et Rhizoma,Paeoniae Radix Rubra,Achyranthis Bidentatae Radix,Spatholobi Caulis,Salviae Miltiorrhizae Radix et Rhizoma,Pheretima,etc.)combined with moxibustion for the treatment of chronic fatigue syndrome(CFS)of qi deficiency and blood stasis type on the basis of qi-collateral theory.Methods A retrospective study was conducted in 60 CFS patients with qi deficiency and blood stasis type.The patients were divided into an observation group and a control group,with 30 patients in each group according to the therapy.The control group was treated with mild moxibustion on Shenque(CV8)point with moxa sticks,and the observation group was treated with Qigui Tongluo Oral Liquid on the basis of treatment for the control group.The course of treatment lasted for 4 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,Fatigue Scale-14(FS-14)scores,serum immunoglobulin IgA,IgM,IgG levels,and cortisol(COR)level in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 96.67%(29/30),and that of the control group was 80.00%(24/30).The intergroup comparison showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores and FS-14 scores of patients in the two groups were significantly decreased compared with those before treatment(P＜0.01),and the effect on decreasing TCM syndrome scores and FS-14 scores in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the serum IgA and IgG levels of the two groups as well as the serum IgM and COR levels of the observation group were significantly increased compared with those before treatment(P＜0.01),and the effect of the observation group on increasing serum IgA,IgM,IgG,and COR levels was significantly superior to that of the control group(P＜0.05 or P＜0.01).(4)During the treatment,there were no significant adverse reactions occurring in the two groups.Conclusion Healthy-qi deficiency and collateral obstruction contribute to the core pathogenesis of CFS.Based on the TCM qi-collateral theory and following the therapeutic principle of replenishing deficiency and unblocking collaterals,Qigui Tongluo Oral Liquid combined with moxibustion for the treatment of CFS patients with qi deficiency and blood stasis type can achieve certain efficacy.The combined therapy could significantly alleviate the clinical symptoms,improve the immunity level,and regulate the neuro-endocrine-immune(NEI)network of the patients.

Objective To observe the clinical efficacy of Shen Shuai Ⅱ Granules combined with integrated Western medicine therapy in patients with primary chronic kidney disease(CKD)in stages 3-4 with the syndrome of spleen and kidney qi deficiency,dampness turbidity and blood stasis,and its effects on expression of serum autophagy related proteins.Methods Totally 88 patients were randomly divided into treatment group and control group,with 44 cases in each group.Both groups were given an integrated Western medicine therapy.On this basis,the treatment group was given Shen Shuai Ⅱ Granules,while the control group was given Shen Shuai Ⅱ placebo,1 bag at a time,twice a day,orally.The treatment for both groups lasted for 24 weeks.The clinical efficacy of the two groups was observed.The TCM symptom scores,serum creatinine(Scr),blood urea nitrogen(BUN),uric acid(UA),blood calcium(Ca2+),blood phosphorus(P3-),parathyroid hormone(PTH),and 24-hour urinary protein quantification(24 UPro)before and after treatment were compared in the two groups.The serum levels of autophagy related protein Beclin-1,Atg7,and LC3-Ⅱ were detected by ELISA before and after treatment in the two groups.Safety indexes of both groups were monitored.Results During the treatment,4 cases fell off in the treatment group and 4 cases in the control group.The total effective rate in the treatment group was 55％(22/40),while that in the control group was 30％(12/40).The therapeutic effect in the treatment group was better than that in the control group(P<0.01).Compared with before treatment,the TCM symptom scores in the treatment group decreased after treatment(P<0.01),the levels of Scr,BUN,UA,P3-,PTH,and 24 UPro decreased(P<0.05,P<0.01),while eGFR increased(P<0.01).The levels of Scr in the control group increased(P<0.05),while eGFR decreased(P<0.01).After treatment,the treatment group had lower various TCM symptom scores,Scr,BUN,UA,P3-,PTH,and 24 UPro levels than the control group(P<0.01,P<0.05),and higher eGFR than the control group(P<0.01).Compared with before treatment,the serum levels of Beclin-1,Atg7,and LC3-Ⅱ increased in the treatment group after treatment(P<0.01,P<0.05),while the serum level of Beclin-1 decreased in the control group after treatment(P<0.01).After treatment,the improvement of the above indicators in the treatment group were better than those in the control group(P<0.01,P<0.05).Correlation analysis showed that Beclin-1,Atg7,and LC3-Ⅱ were negatively correlated with Scr and BUN(P<0.05),and positively correlated with eGFR(P<0.05).There was no obvious adverse reaction in both groups.Conclusion The combination of Shen Shuai Ⅱ Granules and integrated Western medicine therapy for the treatment of primary CKD in stages 3-4 with the syndrome of spleen and kidney qi deficiency,dampness turbidity and blood stasis has confirmed efficacy,which can effectively alleviate clinical symptoms,improve renal function,and delay the progression of CKD.The mechanism may be related to improving the level of autophagy in renal.

Objective:To investigate the efficiency and safety of the pulsatile GnRH therapy in the treatment of male congeni-tal hypogonadotropic hypogonadism(CHH).Methods:We retrospectively analyzed the clinical data on 45 CHH males treated by pulsatile GnRH therapy in our hospital from January 2013 to March 2023.We treated the patients with gonadorelin at 7-15 μg,one pulse/90 min,and followed them up every month in the first 3 months and then every 3 to 6 months after treatment,for an average of 19.1±4.3 months,during which we recorded the height,body weight,penile length,testis volume,Tanner stages,levels of FSH,LH and T,semen parameters and adverse reactions of the patients,followed by comparison of the data obtained with the baseline.Results:The levels of FSH,LH and T of the patients were dramatically elevated after treatment(P<0.01).The T level of the6 ca-ses of cryptorchidism,however,failed to reach the normal value within 18.2±8.6 months of follow-up.Significant improvement was seen in the external genitalia and secondary sexual characteristics of all the patients,and spermatogenesis was observed in the semen in 33 cases(73.3% ),with a mean sperm concentration of(18.2±6.2)106/ml,sperm progressive motility of(19.7±6.5)%,and semen volume of(1.8±0.6)ml.Eight of the cases achieved natural fertility,and another 3 achieved childbirth by assisted re-productive technology.As for adverse events,gynecomastia was observed in 8,subcutaneous induration in 6,and allergic reaction to therapeutic agent in 3 cases.Conclusion:Pulsatile GnRH therapy is an effective and safe strategy for male CHH.However,clini-cians should choose appropriate approaches to different individual cases.

A prokaryotic expression vector for the mutant diphtheria toxin CRM197 was constructed and expressed in Esch-erichia coli cells.Anti-CRM197 antibody concentrations were detected in serum samples of healthy volunteers.The crm 197 gene was codon-optimized in E.coli and cloned into the plasmid pET28a(+)under optimized expression conditions.CRM197 was purified using Ni-NTA spin columns and ion exchange chromatography,and confirmed by western blot analysis.The puri-fied CRM197 was used to detect specific anti-CRM197 antibody levels in serum samples of different age groups.The results showed that soluble codon-optimized CRM197 was successfully expressed under optimized expression conditions.The purity of CRM197 was more than 95％,as determined with Ni-NTA spin columns and ion exchange chromatography,consistent with the single specific bands obtained by western blot analysis and detection of serum levels of the anti-CRM197 antibody.Collec-tively,these results confirmed that the proposed expression strategy achieved high-yield production of soluble CRM197,al-though high levels in human serum may affect evaluation of immune interactions with glycan-CRM197 conjugates for applica-tion as a diagnostic antigen.The diphtheria mutant toxin CRM197 is used in many conjugate vaccines.The synthetic crm 197 gene with codon optimization in pET28a was transformed into E.coli Origami B(DE3)cells.CRM197 was induced by isopro-pyl β-d-1-thiogalactopyranoside and high level accumulation of soluble CRM197 was purified using Ni-NTA spin columns and ion exchange chromatography.The purity of the final prepara-tion reached 95％.CRM197 was used to detect the concentra-tions of the anti-CRM197 antibody in serum samples of healthy volunteers of different ages.The proposed expression strategy yielded high production of CRM197,which could interfere with evaluations of induced immune interactions by glycan-CRM197 conjugates and prohibit application as a diagnostic antigen.

Objective:To investigate the prevalence of albuminuria in Chinese residents aged >35 years and its potential association with cardiovascular disease (CVD).Methods:A total of 34 647 Chinese subjects aged ≥35 years were selected by stratified multi-stage random sampling from 2012 to 2015. Data were collected through questionnaires, physical examinations, and laboratory tests. Albuminuria was categorized into 3 types according to urinary albumin-to- creatinine ratio: normal (<30 mg/g), microalbuminuria (MAU, 30-300 mg/g), and macroalbuminuria (≥300 mg/g). Measurement data were expressed as xˉ±s, and t-tests were used for comparisons between indicators. Qualitative data were expressed as rate or constituent ratio, and the χ2 test or Kruskal-Wallis test was used to examine differences. Logistic regression was used for multivariate analyses. SAS 9.4 software was used for statistical analyses, and P<0.05 was considered statistically significant. Results:The prevalence of abnormal albuminuria was 19.1%; the prevalence was 17.2% for MAU and lower in males (13.8%) than females (20.1%, P<0.01). The risk of CVD was higher among subjects with MAU ( OR=1.23, 95% CI 1.12-1.35) and macroalbuminuria ( OR=1.86, 95% CI 1.50-2.32). When MAU was complicated by hypertension and diabetes mellitus, the CVD risk was 1.76 times higher. Conclusions:The prevalence of MAU is high among Chinese subjects aged 35 years and over. Those with MAU have higher CVD risk, especially those with hypertension and diabetes mellitus.

OBJECTIVE: To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. METHODS: In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m² and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m² or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. RESULTS: During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. CONCLUSIONS The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

Monocytes are key effectors in autoimmunity-related diseases in the central nervous system (CNS) due to the critical roles of these cells in the production of proinflammatory cytokines, differentiation of T-helper (Th) cells, and antigen presentation. The JAK-STAT signaling is crucial for initiating monocytes induced immune responses by relaying cytokines signaling. However, the role of this pathway in modulating the communication between monocytes and Th cells in the pathogenesis of multiple sclerosis (MS) is unclear. Here, we show that the JAK1/2/3 and STAT1/3/5/6 subtypes involved in the demyelination mediated by the differentiation of pathological Th1 and Th17 and the CNS-infiltrating inflammatory monocytes in experimental autoimmune encephalomyelitis (EAE), a model for MS. JAK inhibition prevented the CNS-infiltrating CCR2-dependent Ly6C^hi monocytes and monocyte-derived dendritic cells in EAE mice. In parallel, the proportion of GM-CSF⁺CD4⁺ T cells and GM-CSF secretion were decreased in pathological Th17 cells by JAK inhibition, which in turns converted CNS-invading monocytes into antigen-presenting cells to mediate tissue damage. Together, our data highlight the therapeutic potential of JAK inhibition in treating EAE by blocking the GM-CSF-driven inflammatory signature of monocytes.

Objective: To examine the feasibility and surgical approach of removing type D trigeminal schwannoma through nasal cavity and nasal sinus under endoscope. Methods: Eleven patients with trigeminal schwannoma who were treated in the Department of Otorhinolaryngology, Qilu Hospital of Shandong University from December 2014 to August 2021 were analyzed retrospectively in this study. There were 7 males and 4 females, aged (47.5±13.5) years (range: 12 to 64 years). The neoplasm involved the pterygopalatine fossa, infratemporal fossa, ethmoidal sinus, sphenoid sinus, cavernous sinus, and middle cranial fossa. The size of tumors were between 1.6 cm×2.0 cm×2.0 cm and 5.7 cm×6.0 cm×6.0 cm. Under general anesthesia, the tumors were resected through the transpterygoid approach in 4 cases, through the prelacrimal recess approach in 4 cases, through the extended prelacrimal recess approach in 2 cases, and through the endoscopic medial maxillectomy approach in 1 case. The nasal endoscopy and imaging examination were conducted to detect whether neoplasm recurred or not, and the main clinical symptoms during follow-up. Results: All the surgical procedures were performed under endonasal endoscope, including Gross total resection in 10 patients. The tumor of a 12-year-old patient was not resected completely due to huge tumor size and limited operation space. One patient was accompanied by two other schwannomas located in the occipital region and the ipsilateral parotid gland region originating from the zygomatic branch of the facial nerve, both of which were removed concurrently. After tumor resection, the dura mater of middle cranial fossa was directly exposed in the nasal sinus in 2 cases, including 1 case accompanied by cerebrospinal fluid leakage which was reconstructed by a free mucosal flap obtained from the middle turbinate, the other case was packed by the autologous fat to protect the dura mater. The operation time was (M(IQR)) 180 (160) minutes (range: 120 to 485 minutes). No complications and deaths were observed. No recurrence was observed in the 10 patients with total tumor resection during a 58 (68) months' (range: 10 to 90 months) follow-up. No obvious change was observed in the facial appearance of all patients during the follow-up. Conclusion: Type D trigeminal schwannoma involving pterygopalatine fossa and infratemporal fossa can be removed safely through purely endoscopic endonasal approach by selecting the appropriate approach according to the size and involvement of the tumor.
Male ; Female ; Humans ; Child ; Retrospective Studies ; Endoscopy/methods* ; Nasal Cavity/surgery* ; Neurilemmoma/surgery* ; Cranial Nerve Neoplasms/surgery*

OBJECTIVE: Campylobacter jejuni NCTC11168 is commonly used as a standard strain for flagellar biosynthesis research. In this report, two distinguished phenotypic isolates (CJ1Z, flhA mutant strain, lawn; CJ2S, flhA complemented strain, normal colony) appeared during laboratory passages for NCTC11168. METHODS: Phenotypic assessments, including motility plates, transmission electron microscopy, biofilm formation assay, autoagglutination assay, and genome re-sequencing for these two isolates (CJ1Z, flhA mutant strain; CJ2S, flhA complemented strain) were carried out in this study. RESULTS: Transmission electron microscopy revealed that the flagellum was lost in CJ1Z. Phenotypic assessments and genome sequencing of the two isolates were performed in this study. The capacity for biofilm formation, colony auto-agglutination, and isolate motility was reduced in the mutant CJ1Z. Comparative genomic analysis indicated a unique native nucleotide insertion in flhA (nt, 2154) that caused the I719Y and I720Y mutations and early truncation in flhA. CONCLUSION FlhA has been found to influence the expression of flagella in C. jejuni. To the best of our knowledge, this is the first study to describe the function of the C-terminal of this protein.
Campylobacter jejuni/genetics* ; Bacterial Proteins/metabolism* ; Mutation ; Biological Variation, Population

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype