[Clinical application of inferior pancreaticoduodenal artery management in laparoscopic pancreaticoduodenectomy].

Objective: To investigate the clinical effect of proper management of inferior pancreaticoduodenal artery (IPDA) in laparoscopic pancreaticoduodenectomy (LPD). Methods: This is a retrospective case series study. The clinical and pathological data of 70 patients who received LPD due to pancreatic head tumors, periampullary tumors, or distal common bile duct tumors in the Pancreatic Center of the Second Clinical College of Guangzhou University of Chinese Medicine from January to December 2022 were retrospectively collected. There were 47 males(67.1%) and 23 females(32.9%),aged (59.9±12.8)years(range:13 to 87 years).The procedure of IPDA exposure was as follows:a middle approach was utilized to expose the right half of superior mesenteric artery(SMA) and its right branches between the SMA and superior mesenteric vein(SMV) in superior colonic region. In the subcolonic region,SMA trunk exposure via dissection along the jejunal artery from feet to head and identification the association between IPDA and jejunal artery were prior to IPDA root ligation and dissection. The safety and efficacy of intraoperative IPDA handling were assessed based on surgical videos. Follow-up was carried out in outpatient clinic or by telephone, and outpatient follow-up was conducted once every 1 to 3 months after surgery. Results: The percentage of total LPD was 98.6%(69/70),with all patients achieving R0 resection. Nine cases(12.9%) were involved in combined vascular resection and reconstruction,with 1 case (1.4%) requiring additional upper abdominal incision for vascular and gastrointestinal reconstruction,while the remaining eight cases (11.4%) were completed laparoscopically. The mean operative time was (432.7±115.4)minutes(range:282 to 727 minutes),and the mean blood loss was (140.0±125.7)ml(range:20 to 800 ml). Only two patients(2.9%) received fresh frozen plasma transfusion,with an average volume of 650 ml. Reliable ligation and safe handling of the IPDA were achieved in 91.4%(64/70) of cases, with 8.6%(6/70) suffering from IPDA injury-related bleeding. No one was converted to opened surgery. Pathologically,the mean tumor size was (3.3±1.6)cm (range:1 to 7 cm),and the mean number of harvested lymph nodes was 17.0±7.3(range:0 to 46). Lymph node metastasis was observed in 13 cases (18.6%). Five cases (13.2%) developed grade B pancreatic fistula,while no grade C pancreatic fistula occurred. Other complications included bile leakage in one case(1.4%),delayed gastric emptying in two cases(2.9%), lymphatic leakage in 2 cases(2.9%),intra-abdominal infection in 9 cases(12.9%),and fat liquefaction of surgical incision in 1 case(1.4%). Two cases(2.9%) experienced postoperative intra-abdominal bleeding,one due to mesangial bleeding of lesser curvature of the stomach and the other due to oozing from the hepatic arterial sheath. These bleeding events were not concerned with IPDA. The average length of postoperative hospital stay was (15.2±4.6)days(range:9 to 28 days). Conclusion: Proper intraoperative management of IPDA in LPD might reduce IPDA-related bleeding during and after surgery and improve the safety of LPD.

[The relationship between group B streptococcus genital infection and premature rupture of membrane].

OBJECTIVE: To investigate the relationship between the group B streptococcal (GBS) genital infection of the pregnant women and premature rupture of membrane (PROM). METHODS: Five hundred and eighty seven cases in our hospital maternity clinic or hospital delivery of pregnant women were enrolled from October 2014 to December 2014, including 189 cases of pregnant women with PROM as the observation group and 398 cases of pregnant women without PROM as a control group.GBS in their rectum and vagina secretion was separated and tested by using Group B Streptococcus Chromogenic Agar. RESULTS: Fifty eight cases were detected GBS positive in all 587 pregnant women.The positive rate was 9.9%.In 189 cases of PROM, 37 cases were GBS positive and the positive rate was 19.6%.While in 398 cases of normal pregnant women, 21 cases were positive and the positive rate was 5.3%.The difference has statistically significant (P<0.01). CONCLUSION: GBS infection may be a risk factor for the occurrence of PROM.Psychological counseling, health education and antibiotics should be applied to the GBS positive pregnant women as a preventive strategy.

A requirement of serotonergic p38α mitogen-activated protein kinase for peripheral immune system activation of CNS serotonin uptake and serotonin-linked behaviors.

Alterations in central serotonin (5-hydroxytryptamine, 5-HT) neurotransmission and peripheral immune activation have been linked to multiple neuropsychiatric disorders, including depression, schizophrenia and autism. The antidepressant-sensitive 5-HT transporter (SERT, SLC6A4), a critical determinant of synaptic 5-HT inactivation, can be regulated by pro-inflammatory cytokine signaling. Systemic innate immune system activation via intraperitoneal lipopolysaccharide (LPS) injection rapidly elevates brain SERT activity and 5-HT clearance. Moreover, the pro-inflammatory cytokine interleukin (IL)-1ß rapidly stimulates SERT activity in raphe nerve terminal preparations ex vivo, effects that are attenuated by pharmacological p38 MAPK inhibition. To establish a role of serotonergic p38α MAPK signaling in LPS/IL-1ß-induced SERT regulation and attendant behavioral responses, we pursued studies in mice that afford conditional elimination of p38α MAPK in 5-HT neurons (p38α(5HT-)). We found p38α(5HT-) and control (p38α(5HT+)) littermates to be indistinguishable in viability and growth and to express equivalent levels of SERT protein and synaptosomal 5-HT transport activity. Consistent with pharmacological studies, however, IL-1ß fails to increase SERT activity in midbrain synaptosomes prepared from p38α(5HT-) animals. Moreover, although LPS elevated plasma corticosterone and central/peripheral pro-inflammatory cytokines in p38α(5HT-) animals, elevations in midbrain SERT activity were absent nor were changes in depressive and anxiety-like behaviors observed. Our studies support an obligate role of p38α MAPK signaling in 5-HT neurons for the translation of immune activation to SERT regulation and 5-HT-modulated behaviors.

Up-regulation of HLA-G expression in cervical premalignant and malignant lesions.

The human leukocyte antigen G (HLA-G) molecule, a non-classical major histocompatibility complex class I antigen, exhibits highly limited tissue distribution and gene variation. Recent studies indicate strong immunoinhibitory properties in tumor cells that may favor their escape from anti-tumor immune responses. However, the role of HLA-G in cervical premalignant and malignant lesions has not been defined clearly. In our study, HLA-G expression was studied in cervical tissue from 119 patients with lesions and 22 normal cervical tissue specimens by immunohistochemistry. HLA-G was expressed in 45% (54/119) of cervical lesion-containing tissues while it was rarely detectable (0/22) in the control specimens (P = 0.000). ROC curve analysis showed that HLA-G has an area under the curve (AUC) of 0.694. Furthermore, we investigated soluble HLA-G expression in the plasma of 172 patients with cervical lesions and 20 healthy controls. Significant increases were also observed in soluble HLA-G levels (median, 191.4 vs 45.18 U/ml, P < 0.001). The relative operating characteristic (ROC) curves for soluble HLA-G (sHLA-G), squamous cell carcinoma (SCC), and carbohydrate antigen 125 (CA125) show an AUC of 0.710, 0.634, and 0.588, respectively. At the cut-off values of 108.20 U/ml for sHLA-G, 1.5 ng/ml for SCC, and 35 U/ml for CA125, the sensitivity was 73.30%, 47.83%, and 44.83%, respectively. The detection of soluble HLA-G in plasma may have significance in the early detection of cervical malignant lesions.

The role of the third beta strand in gp120 conformation and neutralization sensitivity of the HIV-1 primary isolate DH012.

Neutralization of HIV-1 primary isolates has been a tremendous challenge for AIDS vaccine development. Here, we identify a single amino acid change (T198P) in gp120 that alters the neutralization sensitivity of the primary isolate DH012 to antibodies against multiple neutralization epitopes that include the V3, CD4-induced, and CD4 binding sites in gp120. This mutation is located in the V1/V2 stem region that forms the third beta strand (beta3) of the bridging sheet of gp120. The conformation of variable loops, especially V1/V2 and V3, was proposed to regulate the accessibility of these neutralization epitopes. The results of this study indicate a direct association between the V1/V2 and V3 loops of DH012 gp120. The single amino acid mutation T198P in the beta3 severely compromises the interaction between the V1/V2 and V3 loops. These results suggest that interaction of V1/V2 and V3 can mask the neutralization epitopes and that the beta3 plays a critical role in determining the neutralization sensitivity by modulating the interaction. This study provides an insight into why primary isolates are relatively resistant to antibody neutralization and might facilitate the development of anti-HIV strategies against HIV-1 infection.

Studies on mode of detection of leprosy in China during the years 1981-1998.

Along with the nationwide economic reform initiated in the early 1980s and the rapid decrease of leprosy endemic after the implementation of multi-drug therapy (MDT), the leprosy programme changed from 'vertical' to 'horizontal'. An evolution in the mode of detection of leprosy cases has consequently taken place. Based on the nationwide registration of newly detected cases, the profile of patients at detection has been studied. The proportions of cases corrected significantly with calendar years in detection by dermatological clinics, contact checks, 'clue survey' and mass survey, showing a significant increase in percentage of cases detected through dermatological clinics and contact checks, and decreases through 'clue survey' and mass survey. Detection of cases through dermatological clinics and voluntary reporting have become the main modes of case-finding during 1997-1998, accounting for 37.3% and 28.6%, respectively, where contact check accounts for only 9.1%. In areas with good dermatological services, a significantly higher proportion (75.9%) of cases was detected through dermatological clinics, where voluntary reporting and 'clue survey' were the main modes of detection in endemic areas. As regards confirmation of diagnosis, the great majority of cases were confirmed by leprosy units, even though they were detected in various other situations. Only 6.5% of leprosy cases were detected and subsequently confirmed by doctors in dermatologic clinics. The present modes of detection and their relation to demographical, epidemiological, clinical factors and health services are discussed. This study emphasizes the cardinal importance of the dermatological clinics in the detection of leprosy cases in China at the present time and hence the need to strengthen the training of doctors in these clinics, while continuously encourage their involvement in leprosy control.

Selective MT(2) melatonin receptor antagonist blocks melatonin-induced antinociception in rats.

The present study was undertaken to assess the effects of intracerebroventricular (i.c.v.) luzindole (a selective MT(2) melatonin receptor antagonist) and prazosin (a selective MT(3) melatonin receptor antagonist) on melatonin-induced antinociception, so as to clarify which of melatonin receptor subtypes within the central nervous system (CNS) was mediating antinociception. The pain threshold of rats was measured by the hot water (50 degrees C) tail-flick test. It was found that intraperitoneal (i.p.) melatonin (30, 60, 120 mg/kg) resulted in a dose-dependent antinociception. Luzindole (50, 100 microgram) administered intracerebroventricularly antagonized significantly the antinociceptive effect induced by i.p. melatonin (120 mg/kg), whereas prazosin (50 microgram) did not. Neither luzindole (100 microgram, i.c.v.) nor prazosin (50 microgram, i.c.v.) affected the nociceptive threshold when given alone. The results suggest that melatonin-induced antinociception is mediated through the MT(2) melatonin receptor subtype within the CNS.

Role of aminoglycoside 6'-acetyltransferase in a novel multiple aminoglycoside resistance of an actinomycete strain #8: inactivation of aminoglycosides with 6'-amino group except arbekacin and neomycin.

From a rare actinomycete strain #8 isolated from soil as arbekacin (ABK) resistant, we cloned a gene segment (0.9 kb) conferring multiple resistance to aminoglycoside (AG) antibiotics with 6'-NH2 including semisynthetic ones except ABK and neomycin (NM). Enzymatic modification using cell free extracts from Streptomyces lividans TK21/pANT-S2 carrying the cloned gene revealed that the gene coded for an AG 6'-acetyltransferase [AAC(6')] capable of acetylating all of the tested AGs with 6'-NH2 including semisynthetic ones and astromicin. The substrate specificity of the enzyme was thus similar to that of AAC(6')-Ie of Enterococcus faecalis. Antibiotic assay revealed a weak but clear antibiotic activity of 6'-N-acetylABK (8% of ABK activity) in contrast with substantial inactivation by the AAC(6') of the other AGs including amikacin and isepamicin. The NM acetylation by the AAC(6') also did not result in NM inactivation. It seems thus likely that AAC(6')-dependent resistance to ABK and NM, if it emerges, will remain at low level.

Supraspinal hyperalgesia and spinal analgesia by [Phe1psi(CH2-NH)Gly2]nociceptin-(1-13)-NH2 in rat.

[Phe1psi(CH2-NH)Gly2]nociceptin-(1-13)-NH2, a pseudopeptide analog of nociceptin, was originally seen as an antagonist of nociceptin receptors. In the present study, it was observed that intracerebroventricular (i.c.v.) injection of this pseudopeptide (1, 5, 10 microg) significantly decreased the tail-flick latency of rats, indicating a hyperalgesic effect, while intrathecal (i.t.) injection of it (1, 2.5, 10 microg) dramatically increased the tail-flick latency, indicating an analgesic effect. This strengthened the in vivo evidence that [Phe1psi(CH2NH)Gly2]nociceptin-(1-13)-NH2 might be an agonist of nociceptin receptors.

Effects of orphanin FQ on endomorphin-1 induced analgesia.

Orphanin FQ (also known as nociceptin) is a 17-amino-acid peptide which acts as a potent endogenous agonist of the orphan opioid receptor-like (ORL1) receptor. Endomorphin-1, a 4-amino-acid peptide discovered recently, is a potent and selective endogenous agonist for the mu-opiate receptor. In the present study, the effect of OFQ or/and endomorphin-1 on the response to noxious thermal stimuli was observed using the tail-flick test in rats. Intracerebroventricular (i.c.v.) administration of OFQ (1, 5 microg) could shorten tail-flick latency; In contrast, intrathecal (i.t.) administration of OFQ (1, 2 or 10 microg) could increase the latency; i.c.v. (1, 2, 5 microg) or i.t. (0.2, 2, 5 microg) administration of endomorphin-1 dose-dependently increased the latency, indicating an analgesic effect. Furthermore, OFQ (0.1-5 microg) when intraventricularly injected together with endomorphin-1 (5 microg), could dose-dependently reverse the analgesia induced by the latter. On the contrary, OFQ (1 microg) intrathecally injected together with endomorphin-1 (0.2 microg) could further increase the tail-flick latency. The results showed that OFQ at the supraspinal level produces hyperalgesia and is antagonistic to endomorphin-1, while at the spinal level it produces analgesia and is synergic with endomorphin-1. Different interaction mechanism between OFQ and endomorphin-1 in the brain and the spinal cord is thus suggested.

Distinct effect of intracerebroventricular and intrathecal injections of nociceptin/orphanin FQ in the rat formalin test.

Nociceptin/orphanin FQ (nociceptin/OFQ), a newly discovered heptadecapeptide has been regarded as an endogenous ligand for orphan opioid receptor. The present study was designed to investigate the effect of nociceptin/OFQ on pain response and opioid analgesia in the rat formalin test. The results showed that intracerebroventricular injection of 1 microg nociceptin/OFQ enhanced the pain response, and 0.1 or 0.5 microg nociceptin/OFQ had no effect on formalin-induced pain. When 0.1 or 1 microg nociceptin/OFQ were used together with mu-, delta-, or kappa-opioid receptor agonists, endomorphin-1, DSLET or U50488H, respectively, it attenuated mu- and kappa- but not delta-receptor mediated analgesia. On the other hand, intrathecal injection of nociceptin/OFQ (0.1, 1 and 5 microg) reduced the pain response in the formalin test. In conclusion, nociceptin/OFQ potentiated formalin-induced pain response and antagonized opioid analgesia in the rat brain but inhibited pain response in the spinal cord.

[Effect of OFQ injection into intracerebroventricular and preoptic area on blood pressure and heart rate in rats].

Orphanin FQ (OFQ) is a novel peptide comprised of an amino acid sequence very similar to that of dynorphin A. In the present investigation the effect of OFQ on cardiovascular activities was studied. Introcerebroventricular (icv) injection of OFQ at doses of 1 and 10 micrograms produced significant decrease in heart rate (HR) and mean arterial pressure (MAP). Icv pretreatment with naloxone could not prevent the hypotensive and bradycardial response produced by 1 microgram OFQ. Injection of 1 microgram OFQ preoptic area (POA) also caused a profound decrease of MAP and HR. These results indicate that OFQ can inhibit cardiovascular activities which are not mediated by mu, delta and kappa receptors. POA may be one of the target areas of these inhibitory effects.

Effects of fenfluramine combined with electroacupuncture on monoamine release in periaqueductal gray of rat brain.

AIM: To study the changes of monoamines in ventrolatoral periaqueductal gray of rat brain before and after electroacupuncture (EA) analgesia (EAA) was enhanced by fenfluramine (Fen), a 5-hydroxytryptamine (5-HT) releaser. METHODS: Monoamines were collected by in vivo microdialysis and measured by HPLC connected with electrochemical detector. RESULTS: The level of norepinephrine (Nor) after EA was decreased (P < 0.05 vs NS group). The contents of 5-HT, 5-hydroxyindol acetic acid (5-HIAA), dopamine (DA), and homovanillic acid (HVA) in periaqueductal gray dialysate were increased (P < 0.05 vs NS group). When Fen was combined with EA, the level of 5-HT and 5-HIAA were further increased (P < 0.05 vs NS + EA group). There was no obvious change of Nor, DA, and HVA. CONCLUSION: Fen potentiating EAA may be related to further activation of serotoninergic system.

[Effect of intrathecal injection of dopamine receptor agonists/antagonists on pain and acupuncture analgesia in rats].

Some selective dopamine receptor agonists and antagonists were tested on rat tail flick model to investigate the role of D1 and D2 dopamine receptor in pain and acupuncture analgesia (AA). It was found that intrathecal administration (i.t.) of D2 receptor agonist LY171555 or D1/D2 receptor agonist apomorphine increased pain threshold and had a potentiating effect on AA. In contrast, D1 receptor agonist SKF38393 had no effect. It D1 receptor antagonist SCH23390 or D2 receptor antagonist sulpiride attenuated the effect of AA. The results suggest that D2 receptor is involved in pain modulation and activation of D2 receptor and enhances AA in the spinal cord, while such effect is absent in D1 receptor and inactivation of D1 receptor attenuates AA.

[Effect of orphanin FQ on acupuncture analgesia and noxious stimulation in the periaqueductal gray].

Orphanin FQ (OFQ) is a newly-discovered neuropeptide which shares great similar sequence with endogenous opioid peptide but with different functions. The present study was to investigate the role of OFQ microinjected in the periaqueductal gray (PAG) on pain threshold and acupuncture analgesia (AA) using tail flick tests. The results show that the hyperalgesia of OFQ and its antagonization on AA in PAG are dose-related. OFQ in PAG decreases the enhancing effect on AA induced by ohmefentanyl, a selective mu-receptor agonist. These observations suggest that OFQ in PAG can increase the rat pain sensitivity and antagonize AA.

Antagonistic effect of orphanin FQ on opioid analgesia in rat.

AIM: To study the effect of orphanin FQ (OFQ), a newly discovered heptadecapeptide, on nociception and opioid analgesia. METHODS: The intracerebroventricular (i.c.v.) and intrathecal (i.t.h.) injections were used to give the drugs. The tail-flick model of rats were used to test the pain threshold. RESULTS: OFQ (i.c.v. or i.t.h.) 0.1 microgram had no effect on nociception but 0.5-10 micrograms induces hyper-reaction of rat to noxious electric stimulus; the decapeptide (OFQ1-10 i.c.v.), a fragment of the OFQ, did not affect the pain reaction of rats. Fentanyl (1 microgram, i.c.v. or i.t.h.), a selective mu-receptor agonist, DSLET (5 micrograms, i.c.v. or i.t.h.), a selective delta-receptor agonist, or U50488H (1 microgram, i.t.h.), a kappa-receptor agonist, induced an increase in pain threshold, when OFQ (0.1 or 1 microgram) was added together with one of them (except for the ith injection of DSLET), the increase of pain threshold was reduced obviously. CONCLUSION: OFQ induces hyperalgesia and antagonizes opioid analgesia mediated by mu- and delta-receptors in the brain and by mu- and kappa- but not delta-receptors in the spinal cord of rats.

Orphanin FQ potentiates formalin-induced pain behavior and antagonizes morphine analgesia in rats.

The present study was designed to observe the effect of orphanin FQ (OFQ, also known as 'nociceptin'), a newly-discovered neuropeptide, on pain behavior and morphine analgesia evaluated by formalin test in rats. It was found that intracerebroventricular (i.c.v.) injection of 0.1 microg OFQ had no effect on formalin-induced pain behavior; but 1, 5, 10 or 20 microg OFQ produced prolonged lifting, licking, biting or shaking of the affected paw with higher pain scoring in dose dependent manner. Repeated i.c.v. injection of antisense olignucleotide (ASO) complementary to OFQ receptor but not mismatch olignucleotide (MSO) resulted in the decrease of pain behavior; in such circumstances, OFQ showed no enhancing effect on formalin nociception. OFQ (0.1 or 1 microg, i.c.v.) significantly attenuated morphine analgesia and ASO could validly antagonize the effect of it. Pretreatment with MSO had no such effect. The present results suggest that OFQ enhances the pain behavior of rat and antagonizes morphine analgesia in formalin test.

[Alteration of monoamine contents in microdialysate following droperidol enhanced electroacupuncture].

The monoamine contents in microdialysate from rat brain before and after droperidol (DRO), a dopamine (DA) antagonist, enhanced electroacupuncture-induced analgesia (EA) were measured using techniques of in vivo microdialysis and high performance liquid chromatography with electrochemical detection (HPLC-EC), so as to investigate the monoamine mechanism of the potentiating effect of DRO on acupuncture analgesia (AA). The results showed that the levels of DA and its metabolites homovanillic acid (HVA) in perfusate increased after EA (P < 0.05 or 0.01), and further increased after DRO + EA (P < 0.05 and 0.01, vs EA treatment). A significant decrease in norepinephrine (NE) content after EA (P < 0.01) was observed, but no further change after DRO + EA (P > 0.05, vs EA treatment). The contents of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) we elevated after EA treatment, and a further elevation in 5-HT and 5-HIAA contents induced by DRO + EA was noted. The results in the present study suggest that DRO potentiated AA not only via antagonizing the activity of dopaminergic system, but also by coordinating the activities of other monoamines in the brain.

Preproopiomelanocortin and preprodynorphin mRNA expressions in rat brain after electroacupuncture + droperidol.

AIM: To study the expression of preproopiomelanocortin (POMC) and preprodynorphin (PPD) mRNA following the combination of electroacupuncture (EA) with droperidol (Dro), a dopamine receptor antagonist. METHODS: The brains and spinal cords of Sprague-Dawley rats were sectioned after combination of EA with Dro, and the gene expression was investigated using nonradioactive in situ hybridization histochemistry (ISHH). RESULTS: Ten hours after EA, the POMC mRNA expression was enhanced; the expression was further enhanced when EA was combined with Dro. The expression of PPD mRNA showed regional difference in central nervous system (CNS): in spinal cord, EA enhanced the PPD mRNA expression and the combination of EA with Dro further promoted the expression; in the brain, the PPD mRNA expression after EA or combination of EA with Dro showed no obvious change in most regions (caudate-putamen, accumbens, arcuate nucleus of hypothalamus) or was decreased in supraoptic nucleus. CONCLUSION: Dro combined with EA promoted the expression of POMC mRNA in CNS and PPD mRNA in spinal cord, but reduced or had no effect on PPD mRNA expression in the brain.

[Effect of intrathecal or intracerebroventricular administrition of OFQ on pain threshold and acpuncture analgesia in rats].

Orphanin FQ (OFQ) is a newly discovered 17-amino-acid peptide capable of inducing hyperalgesia. In the present study, the effects of OFQ on basal pain threshold and acupuncture anlgesia (AA) in rats were observed using the tail-flick test. It was found that intrathecal (i.t.) or intracerebroventricular (i.c.v.) administrition of 0.1 microgram OFQ had no effect on basal pain threshold of rats, while 1 microgram OFQ could lower the threshold. However, OFQ at both the doses (0.1 or 1.0 microgram) administered by either i.t. or i.c.v. injection could antagonize AA with that occuring in the brain being more prominent then in the spinal cord. When the rats were repeatedly treated with antisense oligonucleotide to block synthesis of OFQ receptor, pain threshold increased significantly. At such instance, when the OFQ was combined with acupuncture, the effect of AA showed no obvious change. The above results show that the OFQ at small dose has no effect on pain threshold but can lower it at larger dose; while in both cases OFQ can antagonize AA.